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Continuum Audio features conversations with the guest editors and authors of Continuum: Lifelong Learning in Neurology, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. AAN members can earn CME for listening to interviews for review articles and completing the evaluation on the AAN’s Online Learning Center.

Clinical Features and Diagnosis of Normal Pressure Hydrocephalus with Dr. Abhay Moghekar 07/02/2025

Clinical Features and Diagnosis of Normal Pressure Hydrocephalus with Dr. Abhay Moghekar Normal pressure hydrocephalus (NPH) is a clinical syndrome characterized by the triad of gait apraxia, cognitive impairment, and bladder dysfunction in the radiographic context of ventriculomegaly and normal intracranial pressure. Accurate diagnosis requires consideration of clinical and imaging signs, complemented by tests to exclude common mimics. In this episode, Lyell Jones, MD, FAAN speaks with Abhay R. Moghekar, MBBS, author of the article “Clinical Features and Diagnosis of Normal Pressure Hydrocephalus” in the Continuum® June 2025 Disorders of CSF Dynamics issue. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Moghekar is an associate professor of neurology at Johns Hopkins University School of Medicine in Baltimore, Maryland. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today I'm interviewing Dr Abhay Moghekar, who recently authored an article on the clinical features and diagnosis of normal pressure hydrocephalus for our first-ever issue of Continuum dedicated to disorders of CSF dynamics. Dr Moghekar is an associate professor of neurology and the research director of the Cerebrospinal Fluid Center at Johns Hopkins University in Baltimore, Maryland. Dr Moghekar, welcome, and thank you for joining us today. Why don't you introduce yourself to our listeners? Dr Moghekar: Thank you, Dr Jones. I'm Abhay Moghekar. I'm a neurologist at Hopkins, and I specialize in seeing patients with CSF disorders, of which normal pressure hydrocephalus happens to be the most common. Dr Jones: And let's get right to it. I think most of our listeners who are neurologists in practice have encountered normal pressure hydrocephalus, or NPH; and it's a challenging disorder for all the reasons that you outline in your really outstanding article. If you were going to think of one single most important message to our listeners about recognizing patients with NPH, what would that be? Dr Moghekar: I think I would say there are two important messages. One is that the triad is not sufficient to make the diagnosis, and the triad is not necessary to make the diagnosis. You know these three elements of the triad: cognitive problems, gait problems, bladder control problems are so common in the elderly that if you pick 10 people out in the community that have this triad, it's unlikely that even one of them has true NPH. On the other hand, you don't need all three elements of the triad to make the diagnosis because the order of symptoms matters. Often patients develop gait dysfunction first, then cognitive dysfunction, and then urinary incontinence. If you wait for all three elements of the triad to be present, it may be too late to offer them any clear benefit. And hence, you know, it's neither sufficient nor necessary to make the diagnosis. Dr Jones: That's a really great point. I think most of our listeners are familiar with the fact that, you know, we're taught these classic triads or pentads or whatever, and they're rarely all present. In a way, it's maybe a useful prompt, but it could be distracting or misleading, even in a way, in terms of recognizing the patient. So what clues do you use, Dr Moghekar, to really think that a patient may have NPH? Dr Moghekar: So, there are two important aspects about gait dysfunction. Say somebody comes in with all three elements of the triad. You want to know two things. Which came first? If gate impairment precedes cognitive impairment, it's still very likely that NPH is in the differential. And of the two, which are more- relatively more affected? So, if somebody has very severe dementia and they have a little bit of gait problems, NPH is not as likely. So, is gait affected earlier than cognitive dysfunction, and is it affected to a more severe degree than cognitive dysfunction? And those two things clue me in to the possibility of NPH. You still obviously need to get imaging to make sure that they have large ventricles. One of the problems with imaging is large ventricles are present in so many different patients. Normal aging causes large ventricles. Obviously, many neurodegenerative disorders because of cerebral atrophy will cause large ventricles. And there's an often-used metric called as the events index, which is the ratio of the bitemporal horns- of the frontal horns of the lateral ventricles compared to the maximum diameter of the skull at that level. And if that ratio is more than 0.3, it's often used as a de facto measure of ventriculomegaly. What we've increasingly realized is that this ratio changes with age. And there's an excellent study that used the ADNI database that looked at how this ratio changes by age and sex. So, in fact, we now know that an 85-year-old woman who has an events index of 0.37 which would be considered ventriculomegaly is actually normal for age and sex. So, we need to start adopting these more modern age- and sex-appropriate age cutoffs of ventriculomegaly so as not to overcall everybody with big ventricles as having possible NPH. Dr Jones: That's very helpful. And I do want to come back to this challenge that we've seen in our field of overdiagnosis and underdiagnosis. But I think most of us are familiar with the concept of how hydrocephalus could cause neurologic deficits. But what's the latest on the mechanism of NPH? Why do some patients get this and others don't? Dr Moghekar: Very good question. I don't think we know for sure. And it for a long time we thought it was a plumbing issue. Right? And that's why shunts work. People thought it was impaired CSF absorption, but multiple studies have shown that not to be true. It's likely a combination of impaired cerebral blood flow, biomechanical factors like compliance, and even congenital factors that play a role in the pathogenesis of NPH. And yes, while putting in shunts likely drains CSF, putting in a shunt also definitely changes the compliance of the brain and affects blood flow to the subcortical regions of the brain. So, there are likely multiple mechanisms by which shunts benefit, and hence it's very likely that there's no single explanation for the pathogenesis of NPH. Dr Jones: We explored this in a recent Continuum issue on dementia. Many patients who have cognitive impairment have co-pathologies, multiple different causes. I was interested to read in your article about the genetic risk profile for NPH. It's not something I'd ever really considered in a disorder that is predominantly seen in older patients. Tell us a little more about those genetic risks. Dr Moghekar: Yeah, everyone is aware of the role genetics plays in congenital hydrocephalus, but until recently we were not aware that certain genetic factors may also be relevant to adult-onset normal pressure hydrocephalus. We've suspected this for a long time because nearly half of our patients who come to us to see us in clinic with NPH have head circumferences that are more than 90th percentile for height. And you know, that clearly indicates that this started shortly at the time after birth or soon afterwards. So, we've suspected for a long time that genetic factors play a role, but for a long time there were not enough large studies or well-conducted studies. But recently studies out of Japan and the US have shown mutations in genes like CF43 and CWH43 are disproportionately increased in patients with NPH. So, we are discovering increasingly that there are genetic factors that underlie even adult onset in patients. There are many more waiting to be discovered. Dr Jones: Really fascinating. And obviously getting more insight into the risk and mechanisms would be helpful in identifying these patients potentially earlier. And another thing that I learned in your article that I thought was really interesting, and maybe you can tell us more about it, is the association between normal pressure hydrocephalus and the observation of cervical spinal stenosis, many of whom require decompression. What's behind that association, do you think? Dr Moghekar: That's a very interesting study that was actually done at your institution, at Mayo Clinic, that showed this association. You know, as we all get older, you know, the incidence of cervical stenosis due to osteoarthritis goes up, but the incidence of significant, clinically significant cervical stenosis in the NPH population was much higher than what we would have expected. Whether this is merely an association in a vulnerable population or is it actually causal is not known and will need further study. Dr Jones: It's interesting to speculate, does that stenosis affect the flow of CSF and somehow predispose to a- again, maybe a partial degree for some patients? Dr Moghekar: Yeah, which goes back to the possible hydrodynamic theory of normal pressure hydrocephalus; you know, if it's obstructing normal CSF flow, you know, are the hydrodynamics affected in the brain that in turn could lead to the development of hydrocephalus. Dr Jones: One of the things I really enjoyed about your article, Abhay, was the very strong clinical focus, right? We can't just take an isolated biomarker or radiographic feature and rely on that, right? We really do need to have clinical suspicion, clinical judgment. And I think most of our listeners who've been in practice are familiar with the use and the importance of the large-volume lumbar puncture to determine who may have, and by exclusion not have, NPH, and then who might respond to CSF diversion. And I think those of us who have been in this situation are also familiar with the scenario where you think someone may have NPH and you do a large-volume lumbar puncture and they feel better, but you can't objectively see a difference. How do you make that test useful and objective in your practice? What do you do? Dr Moghekar: Yeah, it's a huge challenge in getting this objective assessment done carefully because you have to remember, you know, subconsciously you're telling the patients, I think you have NPH. I'm going to do this spinal tap, and if you walk better afterwards, you're going to get a shunt and you're going to be cured. And you can imagine the huge placebo response that can elicit in our subjects. So, we always like to see, definitely, did the patient subjectively feel better? Because yes, that's an important metric to consider because we want them to feel better. But we also wanted to be grounded in objective truths. And for that, we need to do different tests of speed, balance and endurance. Not everyone has the resources to do this, but I think it's important to test different domains. Just like for cognition, you know, we just don't test memory, right? We test executive function, language, visuospatial function. Similarly, walking is not just walking, right? It's gait speed, it's balance, and it's endurance. So, you need to ideally test at least most of these different domains for gait and you need to have some kind of clear criteria as to how are you going to define improvement. You know, is a 5% improvement, is a 10% improvement in gait, enough? Is 20%? Where is that cutoff? And as a field, we've not done a great job of coming up with standardized criteria for this. And it varies currently, the practice varies quite significantly from center to center at the current time. Dr Jones: So, one of the nice things you had in your article was helpful tips to be objective if you're in a lower-resource setting. For you, this isn't a common scenario that someone encounters in their practice as opposed to a center that maybe does a large volume of these. What are some relatively straightforward objective measures that a neurologist or someone else might use to determine if someone is improving after a large-volume LP? Dr Moghekar: Yeah, excellent question, Dr Jones, and very practically relevant too. So, you need to at least assess two of the domains that are most affected. One is speed and one is balance. You know, these patients fall ultimately, right, if you don't treat them correctly. In terms of speed, there are two very simple tests that anybody can do within a couple of minutes. One is the timed “up-and-go” test. It's a test that's even recommended by the CDC. It correlates very well with faults and disability and it can be done in any clinic. You just need about ten feet of space and a chair and a stopwatch, and it takes about a minute or slightly more to do that test. And there are objective age-associated norms for the timed up-and-go test, so it's easy to know if your patient is normal or not. The same thing goes for the 10-meter walk test. You do need a slightly longer walkway, but it's a fairly easy and well-standardized test. So, you can do one of those two; you don't need to do both of them. And for balance, you can do the 30-second “sit-to-stand”; and it's literally, again, 30 seconds. You need a chair, and you need somebody to watch the patient and see how many times they can sit up and stand up from a seated position. Then again, good normative data for that. If you want to be a little more sophisticated, you can do the 4-stage balance test. So, I think these are tests that don't add too much time to your daily assessment and can be done with even trained medical assistants in any clinic. And you don't need a trained physical therapist to do these assessments. Dr Jones: Very practical. And again, something that is pretty easily deployed, something we do before and then after the LP. I did see you mentioned in your article the dual timed up-and-go test where it's a simultaneous gait and executive function test. And I’ve got to be honest with you, Dr Moghekar, I was a little worried if I would pass that test, but that may be beyond the scope of our time today. Actually, how do you do that? How do you do the simultaneous cognitive assessment? Dr Moghekar: So, we asked them to count back from 100, subtracting 3. And we do it particularly in patients who are mildly impaired right? So, if they're already walking really good, but then you give them a cognitive stressor, you know, that will slow them down. So, we reserve it for patients who are high-performing. Dr Jones: That's fantastic. I'm probably aging myself a little here. I have noticed in my career, a little bit of a pendulum swing in terms of the recognition or acceptance of the prevalence of normal pressure hydrocephalus. I recall when I was a resident, many, many people that we saw in clinic had normal pressure hydrocephalus. Then it seemed for a while that it really faded into the background and was much less discussed and much less recognized and diagnosed, and less treated. And now that pendulum seems to have swung back the other way. What's behind that from your perspective? Dr Moghekar: It's an interesting backstory to all of this. When the first article about NPH was published in the Newman Journal of Medicine, it was actually a combined article with both neurologists and neurosurgeons on it. They did describe it as a treatable dementia. And what that did is it opened up the floodgates so that everybody with any kind of dementia started getting shunts left, right, and center. And back then, shunts were not programmable. There were no antibiotic impregnated catheters. So, the incidence of subdural hematomas and shunt-related infections was very high. In fact, one of our esteemed neurologists back then, Houston Merritt, wrote a scathing editorial that Victor and Adam should lose their professorships for writing such an article because the outcomes of these patients were so bad. So, for a very long period of time, neurologists stopped seeing these patients and stopped believing in NPH as a separate entity. And it became the domain of neurosurgeons for over two or three decades, until more recently when randomized trials started being done early on out of Europe. And now there's a big NIH study going on in the US, and these studies showed, in fact, that NPH exists as a true, distinct entity. And finally, neurologists have started getting more interested in the science and understanding the pathophysiology and taking care of these patients compared to the past. Dr Jones: That's really helpful context. And I guess that maybe isn't rare when you have a disorder that doesn't have a simple, straightforward biomarker and is complex in terms of the tests you need to do to support the diagnosis, and the treatment itself is somewhat invasive. So, when you talk to your patients, Dr Moghekar, and you've established the diagnosis and have recommended them for CSF diversion, what do you tell them? And the reason I ask is that you mentioned before we started recording, you had a patient who had a shunt placed and responded well, but continued to respond over time. Tell us a little bit more about what our patients can expect if they do have CSF diversion? Dr Moghekar: When we do the spinal tap and they meet our criteria for improvement and they go on to have a shunt, we tell them that we expect gait improvement definitely, but cognitive improvement may not happen in everyone depending on what time, you know, they showed up for their assessment and intervention. But we definitely expect gait improvement. And we tell them that the minimum gait improvement we can expect is the same degree of improvement they had after their large-volume lumbar puncture, but it can be even more. And as the brain remodels, as the hydrodynamics adapt to these shunts… so, we have patients who continue to improve one year, two years, and even three years into the course of the intervention. So, we’re, you know, hopeful. At the same time, we want to be realistic. This is the same population that's at risk for developing neurodegenerative disorders related to aging. So not a small fraction of our patients will also have Alzheimer's disease, for example, or go on to develop Lewy body dementia. And it's the role of the neurologist to pick up on these comorbid conditions. And that's why it's important for us to keep following these patients and not leave them just to the neurosurgeon to follow up. Dr Jones: And what a great note to end on, Dr Moghekar. And again, I want to thank you for joining us, and thank you for such a wonderful discussion and such a fantastic article on the clinical diagnosis of normal pressure hydrocephalus. I learned a lot reading the article, and I learned a lot more today just in the conversation with you. So, thank you for being with us. Dr Moghekar: Happy to do that, Dr Jones. It was a pleasure. Dr Jones: Again, we've been speaking with Dr Abhay Moghekar, author of a wonderful article on the clinical features and diagnosis of NPH in Continuum's first-ever issue dedicated to disorders of CSF dynamics. Please check it out. And thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio. /episode/index/show/continuumjournal/id/36660455

Treatment and Monitoring of Idiopathic Intracranial Hypertension With Drs. John Chen and Susan Mollan 06/25/2025

Treatment and Monitoring of Idiopathic Intracranial Hypertension With Drs. John Chen and Susan Mollan Idiopathic intracranial hypertension (IIH), a condition of increased intracranial pressure (ICP), causes debilitating headaches and, in some, visual loss. The visual defects are often in the periphery and not appreciated by the patient until advanced; therefore, monitoring visual function with serial examinations and visual fields is essential. In this episode, Kait Nevel, MD speaks with John J. Chen, MD, PhD, and Susan P. Mollan, MBChB, PhD, FRCOphth, authors of the article “Treatment and Monitoring of Idiopathic Intracranial Hypertension” in the Continuum® June 2025 Disorders of CSF Dynamics issue. Dr. Nevel is a Continuum® Audio interviewer and a neurologist and neuro-oncologist at Indiana University School of Medicine in Indianapolis, Indiana. Dr. Chen is a professor of ophthalmology and neurology at the Mayo Clinic in Rochester, Minnesota. Dr. Mollan is an honorary professor of metabolism and systems science in the department of neuro-ophthalmology at University Hospitals Birmingham in Birmingham, United Kingdom. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guests: , Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Nevel: Hello, this is Dr Kate Nevel. Today, I'm interviewing Drs John Chen and Susan Mollan about their article on treatment and monitoring of idiopathic intracranial hypertension, which appears in the June 2025 Continuum issue on disorders of CSF dynamics. Drs Chen and Mollan, welcome to the podcast. And please, could you introduce yourselves to the audience? Dr Chen: Hello, everyone. I'm John Chen, one of the neuro-ophthalmologists at the Mayo Clinic. Thanks for having us here. Dr Mollan: Yeah, it's great to be with you here. I'm Susan Mollan. I'm a consultant neuro-ophthalmologist in Birmingham, England. Dr Nevel: Wonderful. So great to have you both here today, and our listeners. To start us off, talking about your article, can you share with us what you think is the most important takeaway from your article for the practicing neurologist out there? Dr Chen: Yeah, so our article talked about the treatment and monitoring of IIH. And I think one takeaway point is, IIH is becoming much more prevalent now that there's this worldwide obesity epidemic with obesity having- essentially being the largest risk factor for IIH other than female. It's really important to monitor vision because vision loss is often peripheral vision loss at first, which the patient may be completely unaware of. And so, it's important to pair up with an ophthalmologist so you can monitor the papilledema of the visual fields and make sure they don't get permanent vision loss. And in the article, we also talk about- there's been changes in the treatment of severe IIH, where traditionally, we used VP shunts; but there's been a trend toward using more venous sinus stenting in addition to the traditional surgeries. Dr Nevel: Great, thank you. I think probably most of our listeners or a lot of neurologists out there have a pretty good understanding of kind of the basics of the IIH. But can you kind of just go over a few key characteristics of IIH, and maybe some things that are less commonly known or things that are maybe just been kind of better understood over the past decade, perhaps? Dr Mollan: Yes, certainly. I think, as Dr Chen said, it's because this condition is becoming more prevalent, people recognize it. I think it's- we like to go back to the diagnostic criteria so that we're making a very accurate diagnosis. So, the patients may come in to the emergency room with, say, papilledema that's been identified elsewhere or crashing headaches. And it's important to go through that sort of diagnostic pathway, taking a blood pressure, taking a full blood count to make sure the patient is anemic, and then moving forward with that confirmation of papilledema into urgent neuroimaging, whether it's CT or MRI, but including venography to exclude a venous sinus thrombosis. And then if you have no structural lesion that's causing the raised ICP, it's moving forward with your lumbar puncture and carefully checking those pressures. But the patients may not only have crashing headache, they often have pulsatile tinnitus and neck pain. I think some of the features that we're now recognizing is the systemic metabolic effects that are unique to IIH. And so, there's an increased risk of cardiometabolic disease that's over and above what is conferred by obesity. Also, our patients have a sort of maternal health burden where they get impaired fertility, gestational diabetes and preeclampsia. And there's also an associated mental health burden, amongst other things. So we're really starting to understand the spectrum of the disease a bit more. Dr Nevel: Yeah, thank you for that. And that really struck me in your article, how important it is to be aware of those things so that we're making sure that we're managing our whole patient and connecting them with the appropriate providers for some of those other issues that may be associated. For the practicing neurologist out there without all the neuro-ophthalmology equipment, if you will, what should our bedside exam focus on to help us get maybe an early but accurate picture of the patient's visual function when we suspect IIH to be at play, perhaps before they can get in with the neuro-ophthalmologist? Dr Chen: Yeah, I think at the bedside you can still check visual acuity and confrontational visual fields, you know, with finger counting. Of course, you have to know that those are, kind of, crude kind of ways of screening. With papilledema, oftentimes the visual acuity is intact. And the confrontational visual fields aren't as sensitive as automated perimetry. Another important thing will be to do your direct ophthalmoscope and look at the amount of papilledema. If it's grade one or two papilledema on the more mild side, it's actually not vision threatening. It's the higher degrees of papilledema that can cause rapid vision loss. And so, if you look in and you see grade one papilledema, obviously you need to do the full workup, the MRI, MRV, lumbar puncture. But in terms of rapidly getting to an ophthalmologist to screen for vision loss, it's not going to be as important because you're not going to have vision loss at that low grade. If you look in and you see this rip-roaring papilledema, grade five papilledema, that patient is going to be at very severe risk of vision loss. So, I think that exam, looking at the optic nerve can be very helpful. And of course, talking to the patient about symptoms; is there decreased vision Is there double vision from a sixth nerve palsy? Are there transient visual obscurations which would indicate at least a higher degree of papilledema? That'd be helpful as well. Dr Nevel: Great, thank you. And when the patient does get in with a neuro-ophthalmologist, you talk in your article and, of course, in clinical practice, how OCT testing is important to monitor in this condition. Can you provide for the listeners the definition of OCT and how it plays a role in monitoring patients with IIH? Dr Mollan: Sure. So, OCT is short for optical coherence tomography imaging, and really the eye has been at the forefront of OCT alone. Our sort of cardiology colleagues are catching up on the imaging of blood vessels. But what it allows us to do is give us really good cross-sectional, anatomical-level changes that we can see both in the retina and also at the optic nerve head. And it gives us some really good measurements. It's not so good at sort of saying, is this definitely papilledema or not? That sort of lower end of disc elevation. But it is very good at ruling out what we call the pseudopapilledema. So, things like drusens or these other little masses we find underneath the optic nerve head. But in terms of monitoring, because we can longitudinally take these images and the reproducibility is pretty good at the optic nerve head, it allows us to see whether there's direct changes: either the papilledema getting worse or the papilledema getting better at the optic nerve head. It also gives us some indication of what's going on in the ganglion cell layer complex. And that can be helpful when we're thinking about sort of looking at structure versus function. So, ophthalmologists in general, we love OCT; and we spend much more time nowadays looking at the OCT than we really do the back of the eye. And it's just become critical for patients with papilledema to be able to be very accurate from visit to visit to see what's changing. Dr Nevel: How do you determine how frequently somebody needs to see the neuro-ophthalmologist with IIH and how often they need that OCT evaluation? Dr Chen: Once the diagnosis of IIH is made, how often they need to be seen and how frequent they need to be seen depends on the degree of papilledema. And again, OCT is really nice. You can quantify it and then different providers can actually use the same OCT numbers, which is super helpful. But again, if it's grade three papilledema or higher, or article thickness of 200 or higher, I tend to follow them a little bit more closely, trying to treat them more aggressively. Try to get the papilledema down into a safer zone. If it's grade one or two papilledema, we see them less frequently. So, my first visit might be three months out. They come with grade five papilledema, I'm seeing them within a few days to make sure that's papilledema’s come down quickly because we're trying to decide, are they going to need surgery or not? Dr Nevel: Yeah, great. And that's a nice segue into talking a little bit about how we treat patients with IIH after the diagnosis is confirmed. And I'd like to just point out you have a very lovely figure in your article---Figure 5-6,---that I'd like to direct our listeners to read your article and check out that figure, which is kind of an algorithm on how we think about the various treatment options for patients who have IIH, which seems to rely a lot on the degree of presence of papilledema and the presence of vision disturbance. Could you maybe walk us through a little bit about how you think about the different treatment options for patients with IIH and when more urgent surgical intervention might be indicated? Dr Mollan: Yeah, sure. We always find it quite hard in any medical specialty to write these kind of flow diagrams because it's really an individual we're looking at. But these are kind of what we’d say is “broad brushstrokes” into those patients that we worry about, sort of, red disease in those patients, more amber disease. Now obviously, even those patients that may not have severe papilledema, they may have crashing headaches. So, they may be an urgent referral themselves because of that. And so, it's nice to try and work out which end of the spectrum you're working with. If we think of the papilledema, Dr Chen's already laid out the sort of lower end of the prison's scale---our grades one, our grades two---that we're less anxious about. And those patients, we would definitely be having discussions about medical management, which includes acetazolamide therapy; but also thinking about weight management. And it may well be that we talk a little bit further about weight management, but I think it's helpful to sort of coach those conversations after you've made a definite diagnosis. And then laying out the risk that's caused, potentially, the IIH in an individual. And then having a sort of open conversation with them about what changes they can have in their lifestyle alongside thinking about medical therapy. There’s some patients with very low levels of papilledema that we decide not to put on medicines initially. As patients progress up that papilledema grade, we're definitely thinking about medical therapy. And our first line from the IIH treatment trial would be using acetazolamide, but we need to be thinking about using appropriate dosing. So, a lot of the patients that I see can be sent to me with very low doses that may be inappropriate for that person. In the IIHTT they used up to four grams daily in a divided dose. And you do need to counsel your patients when you're putting them on acetazolamide because of the side effects. You've got quite a nice table in this article about the side effects. I think if you get the patient on board, that they understand that they will experience side effects, that is helpful because they will expect it, and then possibly tolerate it a bit better. Moving through to that area where we're more anxious, that visual-threatening papilledema. As Dr Chen said, it's sort of like you look in and it's sort of “blood and thunder” in there. And you need to be getting on and encouraging the ophthalmologist to get a formal assessment of the visual field. It's very difficult to determine exactly the level at which- and we talk about the mean deviation in a lot of our research studies. But in general, it's a combination of things: the patient's journey to get to you, their symptoms, what's going on with the visual field, but what's also happening at the OCT. So, we look in and we see that fluid is seeping towards the fovea. We get very anxious, and those patients may not even have enough time for a rapid escalation of acetazolamide. It may well be at the first presentation, which we would term, like, fulminant; that we'd be thinking about surgical intervention. And I think before I stop, the other thing to say is, the surgical landscape is really changing. So, we're having some good studies coming out in terms of stenting. And so, there is a sort of bracket where it may well be that we are thinking about neuroradiological intervention in an earlier case. They may not quite be at that visual-threatening stage, but they may be resistant to medical treatments. Dr Nevel: Thank you for that. What do you think is a potential pitfall or a mistake to avoid, if you will, in the management of patients with IIH? Dr Chen: I think it's- in terms of pitfalls, I think the potential pitfalls I've seen are essentially patients where we don't necessarily create a good patient physician relationship. Where they don't have buy-ins on the treatment, they don't have buy-ins to come back, and they're lost to follow-up. And these patients can be dangerous, because they could have vision threatening papilledema and if not getting the appropriate treatment---and if they're not monitoring the vision---this can lead to poor outcomes. So, I've definitely seen that happen. As Dr Mollan said, you really have to tell them about the side effects from the medications. If you just take acetazolamide, letting them know the paresthesias and the changes in taste and some of these other side effects, they're going to immediately stop the medication. Again, and these medications do work, proven in the IIH treatment trial. So again, I think that patient-physician relationship is very important to make sure they have appropriate follow up. Dr Nevel: The topic of weight loss in this patient population can be tricky, and I know I talked with Susie in a prior interview about how to approach this topic with our patients in a sensitive and compassionate manner. Once this topic is broached, I find many patients are looking for advice on strategies for weight loss, or potentially medications or other interventions. How do you prioritize or think about the different weight loss strategies or treatments with your patients, and how do you think about the way that you recommend these different treatments or not? Dr Mollan: Yeah. I think that's a really great question because we sort of stray here into a specialty that we have not been trained in. One thing I definitely ask my patients: if they've been on a weight loss journey before, and what's worked for them and what's not worked for them. And within our different healthcare systems, we have access to different tiers of weight management approaches. But for the person sitting in front of me, that possibly there may be a long journey to access more professional care, it's about understanding. iIs there things that are free, such as, we have some apps in the National Health Service which are weight management applications where they can actually just start putting in their calories, their daily calorie intake. And those apps can be quite helpful and guiding in terms of targeting areas, but also informing the patient of what types of foods to avoid in their diet and what types of foods to include in their diet. And with some of the programs that are completely complementary, they also sometimes add on things about exercise. But I think it is a really difficult thing to manage as, say, an ophthalmologist or a neurologist, mainly because it's not our area of expertise. And I think we've all got to find, in our local hospitals and healthcare systems, those pathways where the patients may be able to access nutritional support, and sort of behavioral lifestyle therapy support, all the way through to the new medications for weight loss; and also for some people, bariatric surgery pathways. It's a tricky topic. Dr Nevel: So how should we counsel our patients about what to expect in the future in terms of visual outcomes? Dr Chen: I think a lot of that depends on the degree of papilledema when they present. If a patient comes in with grade five papilledema, that fulminant IIH that Dr Mollan had mentioned, these patients can have very severe vision loss. And even if we treat them very aggressively with high-dose medications and urgent surgical interventions, sometimes they can have permanent vision loss. And so, we counsel them that, you know, there's a strong chance that they're going to have a good amount of vision loss. But some patients, we're very surprised and we get a lot of vision back. So, we kind of set expectations, but we're cautiously optimistic that we can get vision back. If a patient presents with more mild papilledema like grade one or two papilledema, they're most likely not going to have any permanent vision loss as long as we're treating them, we're monitoring their vision, they're coming to their follow-ups. They tend to do very well from a vision perspective. Dr Nevel: That's great, thank you. And you know, ties into what you said earlier about really making sure that, you know, we create good- as with any patient, but good physician-patient relationships so that they, you know, trust us and they come to follow up so we can really monitor their vision appropriately. What do you think is going on in research in this area that's exciting? What do you think one of the next breakthroughs or thing that we need to understand the most about treatment and monitoring of IIH? Dr Chen: I think surgically, venous sinus stenting is going to probably take over the bulk of surgeries. We still need that randomized clinical trial, but we have some amazing outcomes with venous sinus stenting. And there's many efforts on randomized clinical trials for venous sinus stenting. So we'll have those results soon. From a medical standpoint, Dr Mollan can actually say, actually, more about this. Dr Mollan: I completely agree. The GLP-1 receptor agonists, the twofold prong approach: one is the weight loss where these patients, you know, have significant weight loss to put their disease into remission; and the other side of it is whether certain GLP-1s have the ability to reduce intracranial pressure. So, a phase 2 study that we undertook here in... /episode/index/show/continuumjournal/id/36660415

Clinical Features and Diagnosis of Idiopathic Intracranial Hypertension With Dr. Aileen Antonio 06/18/2025

Clinical Features and Diagnosis of Idiopathic Intracranial Hypertension With Dr. Aileen Antonio Idiopathic intracranial hypertension (IIH) is characterized by symptoms and signs of unexplained elevated intracranial pressure (ICP) in an alert and awake patient. The condition has potentially devastating effects on vision, headache burden, increased cardiovascular disease risk, sleep disturbance, and depression. In this episode, Teshamae Monteith, MD, FAAN speaks with Aileen A. Antonio, MD, FAAN, author of the article “Clinical Features and Diagnosis of Idiopathic Intracranial Hypertension” in the Continuum® June 2025 Disorders of CSF Dynamics issue. Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida. Dr. Antonio is an associate program director of the Hauenstein Neurosciences Residency Program at Trinity Health Grand Rapids and an assistant clinical professor at the Michigan State University College of Osteopathic Medicine in Lansang, Michigan. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Monteith: Hi, this is Dr Teshamae Monteith. Today I'm interviewing Dr Aileen Antonio about her article on clinical features and diagnosis of idiopathic intracranial hypertension, which appears in the June 2025 Continuum issue on disorders of CSF dynamics. Hi, how are you? Dr Antonio: Hi, good afternoon. Dr Monteith: Thank you for being on the podcast. Dr Antonio: Thank you for inviting me, and it's such an honor to write for the Continuum. Dr Monteith: So why don't you start off with introducing yourself? Dr Antonio: So as mentioned, I'm Aileen Antonio. I am a neuro-ophthalmologist, dually trained in both ophthalmology and neurology. I'm practicing in Grand Rapids, Michigan Trinity Health, and I'm also the associate program director for our neurology residency program. Dr Monteith: So, it sounds like the residents get a lot of neuro-ophthalmology by chance in your curriculum. Dr Antonio: For sure. They do get fed that a lot. Dr Monteith: So why don't you tell me what the objective of your article was? Dr Antonio: Yes. So idiopathic intracranial hypertension, or IIH, is a condition where there's increased intracranial pressure, but without an obvious cause. And with this article, we want our readers---and our listeners right now---to recognize that the typical symptoms and learning about the IIH diagnostic criteria are key to avoiding errors, overdiagnosis, or sometimes even misdiagnosis or underdiagnosis. Thus, we help make the most of our healthcare resources. Early diagnosis and management are crucial to prevent disability from intractable headaches or even vision loss, and it's also important to know when to refer the patients to the appropriate specialists early on. Dr Monteith: So, it sounds like your central points are really getting that diagnosis early and managing the patients and knowing how to triage patients to reduce morbidity and complications. Is that correct? Dr Antonio: That is correct and very succinct, yes. Dr Monteith: And so, are there any more recent advances in the diagnosis of IIH? Dr Antonio: Yes. And one of the tools that we've been using is what we call the optical coherence tomography. A lot of people, neurologists, physicians, PCP, ER doctors; how many among those physicians are well-versed in doing an eye exam, looking at the optic disc? And this is a great tool because it is noninvasive, it is high resolution imaging technique that allows us to look at the optic nerve without even dilating the eye. And we can measure that retinal nerve fiber layer, or RNFL; and that helps us quantify the swelling that is visible or inherent in that optic nerve. And we can even follow that and monitor that over time. So, this gives us another way of looking at their vision and getting that insight as to how healthy is their vision still, along with the other formal visual tests that we do, including perimetry or visual field testing. And then all of these help in catching potentially early changes, early worsening, that may happen; and then we can intervene more easily. Dr Monteith: Great. So, it sounds like there's a lot of benefits to this newer technology for our patients. Dr Antonio: That is correct. Dr Monteith: So, I read in the article about the increased incidence of IIH, and I have to say that I completely agree with you because I'm seeing so much of it in my clinic, even as a headache specialist. And I had a talk with a colleague who said that the incidence of SIH and IIH are similar. And I was like, there's no way. Because I see, I can see several people with IIH just in one day. That's not uncommon. So, tell me what your thoughts are on the incidence, the rising incidence of IIH; and we understand that it's the condition associated with obesity, but it sounds like you have some other underlying drivers of this problem. Dr Antonio: Yes, that is correct. So, as you mentioned, IIH tends to affect women of childbearing age with obesity. And it's interesting because as you've seen that trend, we see more of these IIH cases recently, which seem to correlate with that rising rate of obesity. And the other thing, too, is that this trend can readily add to the burden of managing IIH, because not only are we dealing with the headaches or the potential loss of vision, but also it adds to the burden of healthcare costs because of the other potential comorbidities that may come with it, like cardiovascular risk factors, PCOS, and sleep apnea. Dr Monteith: So why don't we just talk about the diagnosis of IIH? Dr Antonio: IIH, idiopathic intracranial hypertension, is also called pseudotumor cerebri. It’s essentially a condition where a person experiences increased intracranial pressure, but without any obvious cause. And the tricky part is that the patients, they're usually fully awake and alert. So, there's no obvious tumor, brain tumor or injury that causes the increased ICP. It's really, really important to rule out other conditions that might cause these similar symptoms; again, like brain tumors or even the cerebral venous sinus thrombosis. Many patients will have headaches or visual disturbances like transient visual obscurations---we call them TVOs---or double vision or diplopia. The diplopia is usually related to a sixth nerve palsy or an abducens palsy. Some may also experience some back pain or what we call pulsatile tinnitus, which is that pulse synchronous ringing in their ears. The biggest sign that we see in the clinic would be that papilledema; and papilledema is a term that we only use, specifically use, for those optic nerve edema changes that is only associated with increased intracranial pressure. So, performing of endoscopy and good eye exam is crucial in these patients. We usually use the modified Dandy criteria to diagnose IIH. And again, I cannot emphasize too much that it's really important to rule out other secondary causes to that increased intracranial pressure. So, after that thorough neurologic and eye evaluation with neuroimaging, we do a lumbar puncture to measure the opening pressure and to analyze the cerebrospinal fluid. Dr Monteith: One thing I learned from your article, really just kind of seeing all of the symptoms that you mentioned, the radicular pain, but also- and I think I've seen some papers on this, the cognitive dysfunction associated with IIH. So, it's a broader symptom complex I think than people realize. Dr Antonio: That is correct. Dr Monteith: So, you mentioned TVOs. Tell me, you know, if I was a patient, how would you try and elicit that from me? Dr Antonio: So, I would usually just ask the patient, while you're sitting down just watching TV---some of my patients are even driving as this happens---they would suddenly have these episodes of blacking out of vision, graying out of vision, vision loss, or blurred vision that would just happen, from seconds to less than a minute, usually. And they can happen in one eye or the other eye or both eyes, and even multiple times a day. I had a patient, it was happening 50 times a day for her. It's important to note that there is no pain associated with it most of the time. The other thing too is that it's different from the aura that patients with migraines would have, because those auras are usually scintillating and would have what we call the positive phenomena: the flashing lights, the iridescence, and even the fortification that they see in their vision. So definitely TVOs are not the migraine auras. Sometimes the TVOs can also be triggered by sudden changes in head positions or even a change in posture, like standing up quickly. The difference, though, between that and, like, the graying out of vision or the tunneling vision associated with orthostatic hypotension, is that the orthostatic hypotension would also have that feeling of lightheadedness and dizziness that would come with it. Dr Monteith: Great. So, if someone feels lightheaded, less likely to be a TVO if they're bending down and they have that grain of vision. Dr Antonio: That is correct. Dr Monteith: Definitely see patients like that in clinic. And if they have fluoride IIH, I'm like, I'll call it a TVO; if they don't, I’m like, it's probably more likely to be dizziness-related. And then we also have patient migraines that have blurriness that's nonspecific, not necessarily associated with aura. But I think in those patients, it's usually not seconds long, it's usually probably longer episodes of blurriness. Would you agree there, or…? Dr Antonio: I would agree there, and usually the visual aura would precede the headache that is very characteristic of their migraine, very stereotypical for their migraines. And then it would dissipate slowly over time as well. With TVOs, they're brisk and would not last, usually, more than a minute. Dr Monteith: So, why don't we talk about routine imaging? Obviously, ordering an MRI, and I read also getting an MRV is important. Dr Antonio: It is very important because, one: I would say IIH is also a diagnosis of exclusion. We need to make sure that the increased ICP is not because of a brain tumor or not because of cerebral venous sinus thrombosis. So, it's important to get the MRI of the brain as well as the MRV of the head. Dr Monteith: Do you do that for all patients’ MRV, and how often do you add on an orbital study? Dr Antonio: I usually do not add on an orbital study because it's not really going to change my management at that point. I really get that MRI of the brain. Now the MRV, for most of my patients, I would order it already just because the population that I see, I don't want to lose them. And sometimes it's that follow-up, and that is the difficult part; and it's an easy add on to the study that I'm going to order. Again, it depends with the patient population that you have as well, and of course the other symptoms that may come with it. Dr Monteith: So, why don't we talk a little bit about CSF reading and how these set values, because we get people that have readings of 250 millimeters of water quite frequently and very nonspecific, questionable IIH. And so, talk to me about the set value. Dr Antonio: Right. So, the modified Dandy criteria has shown that, again, we consider intracranial pressure to be elevated for adults if it's above 250 millimeters water; and then for kids if it's above 280 millimeters of water. Knowing that these are taken in the left lateral decubitus position, and assuming also that the patients were awake and not sedated during the measurement of the CSF pressure. The important thing to know about that is, sometimes when we get LPs under fluoroscopy or under sedation, then these can cause false elevation because of the hypercapnia that elevated carbon dioxide, and then the hypoventilation that happens when a patient is under sedation. Dr Monteith: You know, sometimes you see people with opening pressures a little bit higher than 25 and they're asymptomatic. Well, the problem with these opening pressure values is that they can vary somewhat even across the day. People around 25, you can be normal, have no symptoms, and have opening pressure around 25- or 250; and so, I'm just asking about your approach to the CSF values. Dr Antonio: So again, at the end of the day, what's important is putting everything together. It's the gestalt of how we look at the patient. I actually had an attending tell me that there is no patient that read the medical textbook. So, the, the important thing, again, is putting everything together. And what I've also seen is that some patients would tell me, oh, I had an opening pressure of 50. Does that mean I'm in a dire situation? And they're so worried and they just attach to numbers. And for me, what's important would be, what are your symptoms? Is your headache, right, really bad, intractable? Number two: are you losing vision, or are you at that cusp where your optic nerve swelling or papilledema is so severe that it may soon lead to vision loss? So, putting all of these together and then getting the neuroimaging, getting the LP. I tell my residents it's like icing on the cake. We know already what we're dealing with, but then when we get that confirmation of that number… and sometimes it's borderline, but this is the art of neurology. This is the art of medicine and putting everything together and making sure that we care and manage it accordingly. Dr Monteith: Let's talk a little bit about IIH without papilledema. Dr Antonio: So, let's backtrack. So, when a patient will fit most of the modified Dandy criteria for IIH, but they don't have the papilledema or they don't have abducens palsy, the diagnosis then becomes tricky. And in these kinds of cases, Dr Friedman and her colleagues, when they did research on this, suggested that we might consider the diagnosis of IIH. And she calls this idiopathic intracranial hypertension without papilledema, IIHWOP. They say that if they meet the other criteria for modified Dandy but show at least three typical findings on MRI---so that flattening of the posterior globe, the tortuosity of the optic nerves, the empty sella or the partially empty sella, and even the narrowing of the transverse venous sinuses---so if you have three of these, then potentially you can call these cases as idiopathic intracranial hypertension without papilledema. Dr Monteith: Plus, the opening pressure elevation. I think that's key, right? Getting that as well. Dr Antonio: Yes. Sometimes IIHWOP may still be a gray area. It's a debate even among neuro-ophthalmologists, and I bet even among the headache specialists. Dr Monteith: Well, I know that I've had some of these conversations, and it's clear that people think this is very much overdiagnosed. So, that's why I wanted to plug in the LP with that as well. Dr Antonio: Right. And again, we have not seen yet whether is, this a spectrum, right? Of that same disease just manifesting differently, or are they just sharing a same pathway and then diverging? But what I want to emphasize also is that the treatment trials that we've had for IIH do not include IIHWOP patients. Dr Monteith: That is an important one. So why don't you wrap this up and tell our listeners what you want them to know? Now's the time. Dr Antonio: So, the- again, with IIH, with idiopathic intracranial hypertension, what is important is that we diagnose these patients early. And I think that some of the issues that come into play in dealing with these patients with IIH is that, one: we may have anchoring bias. Just because we see a female with obesity, of reproductive age, with intractable headaches, it does not always mean that what we're dealing with is IIH. The other thing, too, is that your tools are already available to you in your clinic in diagnosing IIH, short of the opening pressure when you get the lumbar puncture. And I need to emphasize the importance of doing your own fundoscopy and looking for that papilledema in these patients who present to you with intractable headaches or abducens palsy. What I want people to remember is that idiopathic intracranial hypertension is not optic nerve sheath distension. So, these are the stuff that you see on neuroimaging incidentally, not because you sent them, because they have papilledema, or because they have new headaches and other symptoms like that. And the important thing is doing your exam and looking at your patients. Dr Monteith: Today, I've been interviewing Dr Aileen Antonio about her article on clinical features and diagnosis of idiopathic intracranial hypertension, which appears in the most recent issue of Continuum on disorders of CSF dynamics. Be sure to check out Continuum Audio episodes from this and other issues, and thank you to our listeners for joining today. Thank you again. Dr Antonio: Thank you. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio. /episode/index/show/continuumjournal/id/36660405

Radiographic Evaluation of Spontaneous Intracranial Hypotension With Dr. Ajay Madhavan 06/11/2025

Radiographic Evaluation of Spontaneous Intracranial Hypotension With Dr. Ajay Madhavan Recently, sophisticated myelographic techniques to precisely subtype and localize CSF leaks have been developed and refined. These techniques improve the detection of various types of CSF leaks thereby enabling targeted therapies. In this episode, Katie Grouse, MD, FAAN, speaks with Ajay A. Madhavan, MD, author of the article “Radiographic Evaluation of Spontaneous Intracranial Hypotension” in the Continuum® June 2025 Disorders of CSF Dynamics issue. Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California. Dr. Madhavan is assistant professor of radiology at the Mayo Clinic in Rochester, Minnesota. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Grouse: This is Dr Katie Grouse. Today I'm interviewing Dr Ajay Madhavan about his article on Radiographic Evaluation of Spontaneous Intracranial Hypotension, which he wrote with Dr Levi Chazen. This article appears in the June 2025 Continuum issue on disorders of CSF dynamics. Welcome to the podcast, and please introduce yourself to our audience. Dr Madhavan: Hi, thanks a lot, Katie. Yeah, so I’m Ajay Madhaven. I'm a neuroradiologist at the Mayo Clinic in Rochester, Minnesota. I did all my training here, so, I've been here for a long time. And I have a lot of interest in spinal CSF leaks, and I do a lot of that work. And so I'm really excited to be talking about this article with you. Dr Grouse: I'm really excited too. And in fact, it's such a pleasure to have you here talking today on this topic. I know a lot's changed in this field, and I'm sure many of our listeners are really interested in learning about the developments and imaging techniques to improve detection and treatment of CSF leaks, especially since maybe we've learned about this in training. I want to start by asking you what you think is the most important takeaway from your article. Dr Madhavan: Yeah, that's a great question. I think---and you kind of already alluded to it---I think the main thing is, I hope people recognize that this field has really changed a lot in the last five to ten years, through a lot of multi-institutional collaboration and also collaboration between different specialties. We've learned a lot about different types of spinal CSF leaks, how we can recognize the disease, particularly the types of myelography that we need to be using to accurately localize and treat these leaks. Those are the things that have really evolved in the last five to ten years, and they've really helped us improve these patients’ lives. Dr Grouse: Can you remind us of the different common types of spinal leaks that can cause spontaneous intracranial hypotension? Dr Madhavan: Yeah, so there are a number of different spinal CSF leaks, types, and I would say the three most common ones that really most people should try to be aware of and cognizant of are: first, ventral dural tears. So those are, like, just physical holes in the dura. And they're usually caused by little bone spurs that come from the vertebral columns. So, they're often patients who have some degenerative changes in their spine. And those are really very common. Another type of spinal CSF leak that we commonly see is a lateral dural tear. So that's like the same thing in a slightly different location. So instead of being in the front, it's off to the side of the dura laterally. And so, it's also just a hole in the dura. And then the third and most recently discovered type of spinal CSF leak is a CSF-venous fistula. So those are direct connections between the subarachnoid space and little paraspinal vein. And it took us a long time to even realize that this was a real pathology. But now that it's been recognized, we've found that this is actually quite common. So those three types of leaks are probably the three most common that we see. And there's certainly others out there, but I would say over 90% of them fall into one of those three categories. Dr Grouse: That's a great review, thank you. Just as another quick review, as we talk more about this topic, can you remind us of some of the most common or typical brain imaging findings that you'll see in cases of spontaneous intracranial hypotension? Dr Madhavan: Yeah, absolutely. So, when you do a brain MRI in a patient who has spontaneous intracranial hypotension, you will usually, though not always, see typical brain MRI abnormalities. And I kind of think of those as falling into three different categories. So, the first one I think of is dural enhancement or thickening. So that's enlargement or engorgement of the dura, the pachymeninges, and enhancement on postgadolinium imaging. So, that's kind of the first category. The second is that, when you lose spinal fluid volume, other things often expand to take up the space. So, for example, you can get distension or enlargement of the dural venous sinuses, and sometimes you can also get subdural food collections or hematomas. They can arise spontaneously. And I kind of think of those as, you know, you, you've lost the cerebrospinal fluid volume and something else is kind of filling up the space. And then the third category is called brain sagging. And that's a constellation of findings where the posterior fossa structures and the pituitary gland in the cell have become abnormal because you've lost the fluid that normally cushions those structures and causes them to float up. For example, the brain stem will sag down, the distance between the mammillary body and the ponds may become reduced. The suprasellar cistern space may be reduced such that the optic chiasm becomes very close to the pituitary gland, and the prepontine cistern may also become reduced in size. And there are various measurements that can be used to determine whether something is subtly abnormal. But just generally speaking, those are really the three categories of brain MRI abnormalities you'll see. Dr Grouse: That was a great review. And of course, I think in many times when we are thinking about or suspecting this diagnosis, we may be lucky to find those imaging findings to reinforce a diagnosis. Because as it turns out, after reading your article, I was really surprised to find out that in as many as 19% of cases we actually see normal brain imaging, which really was a surprise to me, I have to say. And I think that this really encompasses why spontaneous intercranial hypotension is such a difficult diagnosis to make. I think a lot of us struggle with how far to take the workup when, you know, spontaneous intercranial hypotension is clinically suspected, but multiple imaging studies are normal. Do you have any guidance on how to approach these more difficult cases? Dr Madhavan: So, that's a really good question. And you know, it's- as you can imagine, that's a topic that comes up in most meetings where people discuss this, and it's been a continued challenge. And so, like you said, about 19 or 20% of patients who have this disease can have a, a normal brain MRI. And we've tried to do some work to figure out why that is and how we can identify patients who still have the disease. And I can just provide, I guess, some tips that have helped me in my clinical practice. One thing is, if I ever see a patient with a normal brain MRI where this disease is clinically suspected---for example, maybe they have orthostatic headaches or other very typical symptoms and we don't know why, but their brain MRI is normal---the first thing I do is I try to look back at their old imaging. So many times, these patients who present to us at Mayo, who, when we do their MRI scan here, their brain MRI looks normal… if you really look back at imaging that they've had done elsewhere---maybe even two to three years prior---at the time their symptoms started, they actually had some abnormalities. So, I might see that a patient, two years ago, had dural enhancement that spontaneously resolved; but now they still have symptoms of SIH and they may still have a CSF leak that we can find and treat, but their brain MRI has, for whatever reason, normalized. So, I always start by looking back at old imaging, and I found that to be very helpful. The other thing is, if you see a patient with a normal brain MRI, it's also important to look at their spine MRI because that can provide clues that might suggest that they could still have a spinal CSF leak. And the two things I look for on the spine MRI: one, if there's any extradural CSF. So, spinal fluid outside of where it's supposed to be within the confines of the subarachnoid space. And you know, really, if you see extradural CSF, you know they probably have a spinal fluid leak somewhere. Even if their brain MRI is normal, that just gives you the information that there is a dural tear probably somewhere. And so, in those patients we’ll definitely still proceed to myelography or other testing, even if they have a normal brain MRI. And then the last thing I look for is whether or not they have prominent meningeal diverticula. Patients with CSF venous fistulas almost always have one or more prominent diverticula on their spine along the nerve root sleeves. And that's probably because most of these fistulas come from nerve root sleeve diverticula. We don't completely understand the pathogenesis of CSF venous fistulas, but they're clearly associated with meningeal diverticula. So, if I see a patient who has a normal brain MRI, but I see on their spine MRI that they have many meningeal diverticula that are relatively prominent, that makes me more inclined to be a little bit more aggressive in doing myelography to find a CSF leak. And then I look at other demographic features, too. So, for example, elevated BMI and older age are associated with CSF venous fistulas. So, that can help you determine whether or not it's warranted to go on to more advanced imaging, too. So those are all just a variety of different things that we've used to help us. Dr Grouse: Thank you for sharing that. I wanted to go on to say that, you know, reading your article, of course, as you mentioned, you alluded to the fact there's lots of new imaging modalities out there. It was very illuminating and just an excellent resource for the options that exist and when they're useful. You did a great job summarizing it. And I encourage our readers to check out your article, to refresh themselves, update themselves on what's happened in this space. And of course, we can't summarize them all today, but I was wondering if you could possibly walk us through a hypothetical case of a patient who comes in with a history very suspicious for SIH? How would you approach this patient? Say you have gotten imaging that suggested that there is a spinal fluid leak and now you have to figure out where it is. Dr Madhavan: Yeah. So, you know, I think the most typical scenario it'll be a patient who has been seen by one of my excellent neurology colleagues and they've done a brain MRI and they've made the diagnosis through a combination of clinical information and brain MRI finding. And then the next thing we'll do always is, we'll obtain a spine MRI. So, I think of the purpose of the spine MRI as to determine what type of spinal fluid leak they have. On the spine MRI, if you see extradural CSF, those patients essentially always will have a dural tear. And it may be a ventral dural tear or a lateral dural tear. But if you see extradural CSF, that is pretty much what they have. And conversely, if you don't see extradural CSF---if you just see, for example, many meningeal diverticula, but you don't see anything else particularly abnormal---most of those patients have a CSF venous fistula, just common things being common. So I use the spine MRI to determine what type of leak they have. And then the next thing I think about is, okay, I'm going to do a myelogram on this patient. How do I want to position them? Because it turns out that positioning is probably the most important factor for finding these spinal fluid leaks. You have to have the patient positioned correctly to find the leak that you're trying to localize. And so, if I suspect they have a ventral dural tear, I will always position those patients prone for their myelogram. And I might do one of many different types of myelograms. And, you know, the article talks about things like digital subtraction myelography and dynamic CT myelography. And you can find any of these leaks with any of those techniques, but you just have to have the patient positioned correctly. So, if I think I have a ventral dural tear, I’ll put them prone for the myelogram. If I think they have a lateral dural tear, I'll put them in the cubitus position for the myelogram. And also, if they- if I think they have a CSF-venous fistula, I'll also put them in the decubitus position. Obviously if you're putting them in the decubitus position, you have to decide whether it's going to be left or right side down. So that may require a two-day exam. Sometimes you don't have to; in many cases, we're able to just do everything in one day. But those are all the different factors I think about when I'm trying to determine how I'm going to work those patients up further. So, I really use the spine MRI chiefly to think about what type of leak they're going to have and how I'm going to plan the myelogram. Dr Grouse: That's really great. And it's, I think, really nice to emphasize how much the positioning matters in all this, which I think is not something we've been classically taught as far as the diagnosis of spinal leaks. Another thing I'm really interested in your opinion on is, you talked a lot about how to optimize and what can make you successful at diagnosis. I'm curious what you think one of the easiest mistakes to make or, you know, that we should hopefully avoid when treating patients with this disease. Dr Madhavan: Yeah. And I think, you know, one other thing that's been discussed a lot in this topic… you know, we've talked about the patients with a normal brain MRI. Another barrier or challenge particularly with CSF-venous fistulas is, sometimes they can be very subtle on imaging. So, it's not always you see it very definitive CSF-venous fistula where you can say, like, there's no question, that's a fistula. There are many times where we do a good-quality myelogram and we see something that looks, like, possible for a CSF venous fistula, or probable. If I had to put a number on it, maybe there's a 50 to 70% chance of real. So, in those cases, we end up wondering, like, should we treat this suspected leak? And I think one common mistake or one thing that needs to be looked at further is, how do we handle these patients where we don't know whether the fistula is real or not? That's usually something where I will have a discussion with the patient, and I'm usually just very upfront with him about my interpretation of the imaging. I'll just tell them, we did a good-quality myelogram. You did a great job. We got good images. I don't see anything definitive, but I see this thing that I think has maybe a 60% chance of being real. And then I'll confer with one of my neurology colleagues and we'll decide whether it's worth treating that or not. And we'll just be very upfront with a patient about whether- about the likelihood of its success and what their long-term prognosis is. And oftentimes we let them make the decision. But I think that remains to be one of the big challenges is, how do we treat these patients who have suspected leaks that are not definitive on imaging. Dr Grouse: That sounds absolutely like an important area where there can be problems, so I appreciate that insight. I'm interested what you think in your article would come as the biggest surprise to our listeners who may not have kept up as much with all of the changes that have happened in recent years? Dr Madhavan: One of the things that was certainly, at least, a surprise to me as I was going through my training and learning about this topic is how diverse myelography has really become. You know, when I was a radiology resident, I learned about myelography as this thing that we've been doing for 30 to 40 years. And historically we've used myelograms just to look for degenerative changes: disc bulges, you know, disc herniations and things like that. Now that MRI is more prevalent, we don't use it as much, but it has turned out that it has a very big role in patients with spinal fluid leaks. Furthermore, something that I've learned is just how diverse these different types of myelograms have become. It used to kind of be just that a myelogram is a myelogram is a myelogram, but now we have different types of positioning, different types of equipment that we use. We vary the timing between contrast injection and imaging to optimize success for finding spinal fluid leaks. So, I think many times I talk to people who may not be as familiar with this field and they're surprised at just how diverse that has become and how sophisticated some of the various myelographic techniques have become and how much that really makes a difference in being able to accurately diagnose these patients. Dr Grouse: Well, I can say it was a surprise to me. Even as someone who does treat quite a few patients with this condition, I was surprised to see the breadth of different options that have become available. And then kind of a follow-up to that, what do you think the current area of controversy is in this area of diagnosis and treatment? Dr Madhavan: The biggest ones are ones you've sort of already alluded to. So, one big one is, how far do we go in patients who have a normal brain MRI who still have a clinical suspicion of the disease? And sometimes it's really hard, because sometimes you will find patients who clinically have a very strong case for having spontaneous intracranial hypotension. You look at them, they have very acute-onset orthostatic headaches. There's no better explanation for their symptoms that we know of. And it's hard to know what to do with those patients, because some of them want to continue to undergo diagnostic workup, but you can only do so many myelograms and you can only do so much with this diagnostic workup that requires some radiation dose before it becomes very challenging. That's a major point of just, I guess, ongoing research as to what can we do better for that subset of patients. Fortunately, it's not all of them, it's a subset of them, but I think we could help those patients better in the future as we learn more about the disease. So that's one. And the other one is treating these equivocal findings, like I discussed. And where should our threshold be to treat a patient, and what type of treatment should we do in patients where we don't know whether a leak is real? Should we just do a very noninvasive- relatively noninvasive blood patch? Do we do an embolization where we're leaving a foreign body there? Is it worth sending those patients to surgery? Those are all unanswered questions and things that continue to spark ongoing debate. Dr Grouse: Do you think that there's going to be any new big breakthroughs, or even, do you know of any big developments on the horizon that we should be keeping our eyes out for? Dr Madhavan: You know, I think for... /episode/index/show/continuumjournal/id/36660340

Clinical Features and Diagnosis of Spontaneous Intracranial Hypotension With Dr. Jill Rau 06/04/2025

Clinical Features and Diagnosis of Spontaneous Intracranial Hypotension With Dr. Jill Rau Spontaneous intracranial hypotension reflects a disruption of the normal continuous production, circulation, and reabsorption of CSF. Diagnosis requires the recognition of common and uncommon presentations, careful selection and scrutiny of brain and spine imaging, and, frequently, referral to specialist centers. In this episode, Gordon Smith, MD, FAAN speaks with Jill C. Rau, MD, PhD, author of the article “Clinical Features and Diagnosis of Spontaneous Intracranial Hypotension” in the Continuum® June 2025 Disorders of CSF Dynamics issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Rau is an assistant professor of clinical neurology at the University of Arizona, School of Medicine-Phoenix in Phoenix, Arizona. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Interview with Jill Rau, MD Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Smith: This is Dr Gordon Smith. Today I'm interviewing Dr Jill Rau about her article on clinical features and diagnosis of spontaneous intracranial hypotension, which she wrote with Dr Jeremy Cutsworth-Gregory from the Mayo Clinic. This article appears in the 2025 Continuum issue on disorders of CSF dynamics. I'm really excited to welcome you to the Continuum podcast. Maybe you can start by just telling our listeners a little bit about yourself? Dr Rau: Hi, thanks for having me. I'm really honored to be here, and I really enjoyed writing the paper with Dr Cutsforth-Gregory. I hope you guys enjoy it. I am the director of headache medicine at the Baba Bay Neuroscience Institute at Honor Health in Scottsdale, Arizona. I'm also currently the chair of the special interest group in CSF Dynamics at the American Headache Society, and I've had a special interest in this field since I first watched Dr Linda Gray speak at a conference where she talked about spinal CSF leaks and their different presentations. And they were so different than what I had been taught in residency. They're not just the post-LP headache. They have such a wide variety of presentations and how devastating they can be, and how much impact there is on someone's life when you find it and fix it. And I've been super interested in the field and involved in research since that time. And, yeah. Love it. Dr Smith: Well, thanks for sharing your story. And as I reflected on our conversation ahead of time and have been thinking about this issue… this is a cool topic, and every time I read one of these manuscripts and have the opportunity to speak with one of the authors, I learn a ton, because this was something that wasn't even on the radar when I trained back in the 1800’s. So, really looking forward to the conversation. I wonder if you could really briefly just summarize or remind for everyone the normal physiology about CSF dynamics, you know, production, absorption, and so forth? Dr Rau: So, the CSF is the fluid that surrounds the brain and the spinal cord, and it's contained by the dura, which is like a canvas or a sac that covers that whole brain and spinal cord. And within the ventricles of the brain, the choroid plexus produce CSF. It's constantly producing and then being reabsorbed by the arachnoid granulations and pushed into the venous space, the cerebral sinuses, venous sinuses. And also some absorption and push into the lymphatics that we've just learned about in the past year. This is kind of new data coming out, so always learning more and more about CSF, but we know that it bathes the brain and the spinal cord, helps keep some buoyancy of the brain as well as pushing nutrients in and pulling out metabolic waste. And it sort of keeps the brain in the state of homeostasis that's happy. And so, when there's a disruption of that flow and the amount of fluid there, that disrupts that, that can cause lots of different symptoms and problems for people. Dr Smith: One of the many new things I learned is that even the name of this---spontaneous intracranial hypotension---is misleading. And I think this is clinically relevant, as we'll probably get to in a moment, but can you talk a little bit about this? Is this really like a pressure disorder or a volume disorder? Dr Rau: Yeah. It's almost certainly a volume disorder. We do see in some people that they have low pressure, and it’s still part of the diagnostic criteria. But it's there because if you have a low pressure, if you measure an opening pressure and it's below six, if you're measuring it in the spine in the right place, then you have indication that there's low volume. But there's over 50% of people's opening pressure who have a spinal CSF leak, have all the symptoms and can be fixed. So, they have normal pressure in 50% of the people. So, it is an inaccurate term, hypotension, but it was originally discovered because of the thought that it was a low-pressure situation. Some of the findings would suggest low pressure, but ultimately, we are pretty sure it's a low-volume condition. Dr Smith: Another new thing that I learned that really blew me away is how bad this can be. I did a podcast with Mark Burish about cluster, and I was reminded many cluster patients are pushed to the point of suicidal ideation or committing suicide by the severity of pain. And this sounds like for many patients it's equally severe. Can you maybe paint a picture for our listeners why this is so clinically important? Dr Rau: A large number of people, even people who are known to have leaks because they've had them before or they've releaked, they have a lot of brain fog and cognitive impairment. They often have severe headaches when they're upright. So, orthostatic headache is probably the number one most common symptom, and those headaches are one of the worst headaches out there. When people stand up, their fluid is not supporting the brain and there's an intense amount of pain. And so, they spend a large portion of their lives horizontal. And there's associated symptoms with that, it's not just headache pain and brain fog. There's neck pain. There's often subsequent disorders that accompany this, like partial orthostatic tachycardia syndrome. We don't know if that's because of deconditioning or an actual sequela of the disease, but it's a frequent comorbidity. We have patients that have extreme dizziness with their symptoms, but many patients are limited to hours, if that, upright per day, combined, total. And so they live their lives, often, just in the dark, lots of photophobia, sensitive to the light, really unable to function. It's also very hard to find and so underrecognized that a lot of patients, especially if they don't have that really clinical symptom of orthostatic headache. So, it's often missed. So, they're just debilitated. You know, treatments don't work because it's not a migraine and it's not a typical headache. It's a mechanical issue as well as a metabolic issue and not found, not a lot helps it. Dr Smith: So, you know, I have always thought about this as really primarily an orthostatic symptom. I wonder if you can talk about the complexity of this; in particular, kind of how this evolves over time, because it's not quite that simple. And maybe in doing so, you can give our listeners some pearls on when they should be thinking about this disorder? Dr Rau: A large portion of people do have headache with spinal CSF leak, in particular, spontaneous intracranial hypertension- hypotension, excuse me. And that's something to be thought about, is that there are spontaneous conditions where people have either rupture of the dural sac, or an erosion of the dural sac, or a development of a connection between the dura and the venous system. And that is taking away or allowing CSF to escape. In these instances that patients have spontaneous, there may be a different presentation than if they have, like, a postdural puncture or a chronic traumatic or iatrogenic leak. And we're not sure of that yet, but we're looking into that. Still, the largest presentation is headache, and orthostatic headache is very dominant in the headache realm. But over time, patients’ brains can compensate for that lack of CSF and start overproducing---or at least we think that's probably what's happening. And you may see a reduction in the orthostatic symptoms over time, and you may see an improvement in the radiographic findings. So, there are some interesting papers that have been published that look at these changes over time, and we do see that sometimes within that first three to four months; this is the most common time to see that change. Other patients may worsen. You may actually see someone going from looking sort of normal radiographically to developing more of a SIH-type of picture on the brain. And so it's not predictable which patients have gone from orthostatic to improvement or the other way around, both radiographically and clinically. So, it can be quite difficult to tell. So, for me, if I have a patient that comes to me and they're struggling with headache… if it's orthostatic, very clearly orthostatic: I lay down, I get considerably better or my headache completely goes away. And then when I stand up, it comes on relatively quickly, within an hour. And sometimes it's a worsening-throughout-the-day type of thing, it's lowest in the morning and it worsens throughout the day. These are the times that it's most obvious to think about CSF leak. Especially if that headache onset relatively suddenly, if it onset after a small trauma. Like I've had patients that say, you know, I was doing yoga and I did some twists and I felt kind of a pop. And then I've had this headache that is horrible when I'm upright but is better when I lay down ever since, you know, since that time. That's kind of a very classic presentation of spinal CSF leak or spontaneous intracranial hypotension. Maybe a less common presentation would be someone who comes to you, they've had a persistent headache for a couple years, they kind of remember it started in March of a couple years ago, but they don't know. Maybe it's, you know, it's a little better when they lay down. It may be a little worse when they're up moving around, but so is migraine, and it's a migrainous headache. But they've tried every migraine drug you can think of. Nothing is responding, nothing helps. I'm always looking at patients who are new daily, persistent headaches and patients who aren't responding to meds even if it's not new daily, but they have just barely any response. I will always go back and examine their brain imaging and get full spine to make sure I'm not missing. And you can never be 100% sure, but it's always good to consider those patients to the best of your ability, if that- have that in the back of your mind. Dr Smith: So obviously, goes without saying, this is something people need to have on their radar and think about. And then we'll talk more about diagnostic tools here in a second. But how common is this? If you're a headache doc, you see a lot of patients who have intractable headaches. And how often do you see this in your headache practice? Now you’re- this is your thing, so probably a little more than others, but, you know, how common will someone who sees a lot of headache encounter these patients? Dr Rau: If you see a lot of headache, I mean, currently the thought is it's about 5 in 100,000. That was from a study before we were finding CSF venous fistulas. I think a lot of us think it's more common than that, but it's not super common. We don't have good estimates, but I would guess between 5 and 10 for 100,000 persons, not “persons who come to a tertiary headache clinic with intractable headaches”. So, it's hard to gauge how frequent it is, but I would say it's considerably more frequent than we currently think it is. There's still a group of people with orthostatic headaches that we can't find leaks on; that, once you treat other things that can cause or look for other things that can cause orthostatic headaches. So, there may be even still a pathophysiology out there that is still a leak type. Before 2014, we didn't even know about CSF venous fistulas. And now here we are; like, 50% of them are CSF venous fistulas. So, you know, we're still in a huge learning curve right now. Dr Smith: So, I definitely want to talk about the fistulas in a second. But before moving on, one of the things that I found really interesting is the wide spectrum of clinical phenotype. And we obviously don't have a lot of time to get into all of these different ones, but the one that I was hoping you might talk about---and there's a really great case, and you're on bunch of great case, a great case of this---is brain sagging dementia, not a term I've used before. Can you really briefly just tell our listeners about that, because that's a really interesting story and a great case in your article? Dr Rau: Yeah. So, brain sag dementia is a… almost like an extreme version of a spontaneous intracranial hypotension. Where there is clear brain sag in the imaging---so that's helpful---but the patients present kind of like a frontotemporal dementia. And when this was first started to being determined, you could turn the patient into Trendelenburg, and sometimes they would improve. There are some practitioners that have introduced fluid into the thecal sac and had temporary improvement. Patching has improvement, then they leak again, sometimes not. But the clinical changes with this have been pretty tremendous to be able to identify that that's a real thing. And in some cases, out of Cedars Sinai, you know, who does a lot of the best research in this, they've had lots of cases where they can't find the leak, but there's clear brain sag that fits with our clinical picture of CSF leaks. So, we're on a learning curve. But yeah, this- they really present. They have disinhibition and cognitive impairment that is very similar to frontotemporal dementia. Dr Smith: Well, so let's talk about what causes this. You mentioned CSF venous fistulas. I mean, that was reported now just over a decade ago, it's pretty amazing. That accounts for about half of cases, if I understand correctly. What are the other causes? And then we'll talk more about therapy in a minute, but what causes this? Dr Rau: So, within the realm of spontaneous, you know, we say it's spontaneous. But the spontaneous cases we account for, they can be tears in the dura, which are usually sort of lateral tears in the dura. They can be little places that rubbed a hole, often on an osteophyte from the spine. They can come from these spinal diverticuli. So, I always describe it to my patients like those balls that have mesh and squishy, and you squeeze them in the- through the mesh, there's the extra little bubbling out. If you think of like the dura bubbling, out in some cases, through the framing of the spine, right where the spinal nerve roots come out, they should poke out like wires from the dura. But in many cases they poke out with this extra dura surrounding them, and we call that spinal diverticuli. And if you imagine like the weakening of where you squeeze that, you know, balloon through your fingers, in those locations, that's a very common place to find a CSF leak, and you can imagine that the integrity of the dura there may be less than it would be if it were not being expanded in that direction. And that's often the most common place we see these CSF venous fistulas. So, you can get minor traumas; like I said, it can be spontaneous, like someone just develops a leak one day. It can be rubbed off, and it can be a development of a connection between the dura and the venous system. There are also iatrogenic causes, but we don't consider them spontaneous. But when you're considering your patients for spontaneous cases, you should consider if they've ever had chronic---even long, long time ago---had any spinal implementation, procedures near the spine, spinal injections, LPs in the past, and especially women who've had epidurals in pregnancy. Dr Smith: All right, so we see a patient, positional severe headache, who meets the clinical criteria. Next step, MRI scan? Dr Rau: Yeah. So, the first thing is always to get the brain MRI with and without contrast. Most places will have a SIH or a spinal CSF leak protocol, but you should get contrast because one of the most pathognomonic findings on brain MRI is that smooth diffuse dural enhancement. And that's a really fantastic thing when you find it, because it's kind of a slam dunk. If you find it, then you will see other findings. It almost never exists alone. But if you see that, it's pretty much a spinal CSF leak. But you're also looking for subdural collections, any indication of brain sag. We do have these new algorithms that have come out in the past couple of years that are helpful. They're not exclusionary---you can have negative findings on the brain and still have spinal CSF leak---but the brain MRI is extremely helpful. If it's positive for the findings, it really does help you nudge you in the direction of further investigations and treatments. Dr Smith: And what about those further investigations and treatments, right? So, you see that there's findings consistent with low pressure, and I guess I should say low intracranial CSF volume. Be that as it may, what's the next step after that? Dr Rau: Depends on where you are and what you can do. I almost always will get a full spine MRI: so, C spine, T spine, and L spine separately. Not, you know, we don't want it all in one picture, because we want to get the full view. And you want to get that with at least T2 highly- heavily T2 weighted with fat saturation in at least the sagittal and axial planes. It's really helpful if you can get it in the coronal planes, but we have to have- often have good talks with your radiologist to get the coronal plane. I spoke about the spinal diverticuli earlier, and I want to clarify a little bit of something. The coronal image will show those really nicely. It's interesting, but 44% of people have those. So just having the spinal diverticuli does not indicate that you have a leak. But if you have a lot of those, there may be more likelihood of having leak than if you don't have any of those. So, I will get all of those and I will look at them myself, but I've been looking at them myself for a long time. But a lot of radiologists in community hospitals, especially not- nonneuroradiologists, but even neuroradiologists, this isn't something that's that everybody's been educated about, and we've been learning so much about it so rapidly in the past ten years. It's not easy to do and it's often missed. And if it's not protocoled properly, the fat saturation's not there, it's very hard to see… you can have a leak and not see it. Even the best people, like- it's not always something that's visible. And these CSF venous fistulas that we talked about are never visible on normal MRI imaging. Nonetheless, I will run those because if I can find a leak---and 90% of the ones that are found on MRI imaging are in the thoracic spine. So that's where I spend the most of my time looking. But if you find it, that's another thing to take to your team to say, hey, look, here it is, let's try and do this, or, let's try and do that, or, I've got more evidence. And there... /episode/index/show/continuumjournal/id/36660325

June 2025 Disorders of CSF Dynamics Issue With Dr. Jeremy K. Cutsforth-Gregory 05/28/2025

June 2025 Disorders of CSF Dynamics Issue With Dr. Jeremy K. Cutsforth-Gregory In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Jeremy K. Cutsforth-Gregory, MD, FAAN, who served as the guest editor of the June 2025 Disorders of CSF Dynamics issue. They provide a preview of the issue, which publishes on June 2, 2025. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Cutsforth-Gregory is an associate professor in the department of neurology at Mayo Clinic in Rochester, Minnesota. Additional Resources Read the issue: Subscribe to Continuum®: Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Interview with Jeremy Cutsforth-Gregory, MD Dr Jones: Most of the time when neurologists think about cerebrospinal fluid or CSF, we're thinking about getting a sample so we can test it for biomarkers of infection or inflammation, tumors, more recently neurodegenerative diseases. But there are many patients for whom the CSF isn't a clue to the problem---it is the problem. Today I have the opportunity to interview Dr Jeremy Cutsforth-Gregory, who is the guest editor of our first-ever issue at Continuum on disorders of CSF dynamics. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about subscribing to the journal, listening to verbatim recordings of the articles, and exclusive access to interviews not featured on the podcast. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today I'm interviewing Dr Jeremy Cutsforth-Gregory, who recently served as Continuum's guest editor for our latest issue, which covers disorders of CSF dynamics. Dr Cutsforth-Gregory is an associate professor in the Department of Neurology at Mayo Clinic in Rochester, Minnesota, where he's also the director of the Mayo Clinic CSF Dynamics Clinic and an assistant dean of career advising at the Mayo Clinic School of Medicine. Dr Cutsforth-Gregory, welcome, and thank you for joining us today. Why don't you introduce yourself to our listeners? Dr Cutsforth-Gregory: Thank you so much, Dr Jones. I'm excited to be here and really privileged to have served as the guest editor for this first issue devoted to CSF dynamics. You mentioned my title as director of the CSF Dynamics Clinic, in which we brought together what we think of as the full spectrum of disorders where pressure or flow of the fluid around the central nervous system is off. So, we do CSF leaks, we do intracranial hypertension and normal pressure hydrocephalus, and from that have been able to gain quite a few insights that I'm excited to share with you today. Dr Jones: Yeah. And I'm really grateful for your time. I'm really grateful for this issue. You know, we all learn about disorders of CSF flow in training, but my impression---and maybe you share it, Dr Cutsforth-Gregory---is that many of these patients fall through the cracks. I think there's probably many reasons for this. I think it's in part because some aspects of this practice are relatively new or they're changing rapidly, or some of the disorders are uncommon. And I think many of these require a high degree of coordination between neurologists and neurosurgeons and radiologists. So we thought a Continuum issue dedicated to this would help close some practice gaps that we're pretty confident are out there. I'm really grateful for your leadership of it, and I think it'll come in handy for junior readers and even our more experienced listeners as well. And let's get right to it. You've had a chance now to review all of the articles in the issue and, you know, the latest in the field. What's the biggest thing that you would like to see change in the care of these patients? Dr Cutsforth-Gregory: I think you're right that there is often delay in diagnosis, incorrect diagnosis, misdiagnosis, really across the spectrum of the low pressure, high pressure and normal pressure disorders. And that's what I'd like to see change with this issue, is increased awareness of the really myriad presentations that spontaneous intracranial hypotension can have. It's not all orthostatic headache, although that's common. Similarly, idiopathic intracranial hypertension is misdiagnosed in a third or more cases presenting to ophthalmology clinics. So, it's not just papilledema, high pressure in a certain demographic. And I think the article by Dr Aileen Antonio really goes into the details on how to make an accurate diagnosis and not miss these and not mistreat them. And normal pressure hydrocephalus, the pendulum has really swung between whether this is an entity or isn't an entity. It is. It's patients we can help. The imaging findings are surprisingly common, and the disorder is probably somehow both overcalled on CT scans of the head---cannot rule out normal pressure hydrocephalus, clinical correlation required, we've all seen that report---but also missed opportunities to help patients who have treatable gait, cognitive and bladder disorders. So, if we could improve awareness and increase the accuracy of diagnosis on these three disorders, I will say the mission has really been moved forward. Dr Jones: Thanks for that. Let's start with NPH because again, over my career, I have seen the pendulum swing back and forth in terms of awareness of this disorder and thresholds for diagnosis. What's our latest in terms of the understanding of normal pressure hydrocephalus and how should our listeners think about the approach to diagnosing these patients? Dr Cutsforth-Gregory: I think we all learn that NPH is dementia, gait disorder and urinary incontinence, and that hasn't changed. A good chunk of these patients, perhaps half or more, don't have the full triad, and you do not have to have the full triad for the diagnosis or to justify intervention with permanent CSF diversion through shunt placement. And so, being open to the diagnosis in a patient with a gate apraxia, which is usually the first leading present presenting change which is a gait disorder. Cognitive changes follow that, bladder comes along the way. So, I think anytime you see someone with an unexplained gait disorder that has apraxic features, short steps, three steps to turn, can look a little Parkinsonian but you don't have other Parkinsonism on exam necessarily, we should be thinking about NPH and ordering a good-quality head imaging to look for those features. Dr Jones: Yeah, thanks for that point, Jeremy. It does seem like the pendulum has swung back and forth on the diagnosis of this disorder. And I think in many ways it comes down to having good diagnostic biomarkers. A term that I know… I was only made aware of it a few years ago: disproportionately enlarged subarachnoid space hydrocephalus, or DESH. So, tell us a little bit more about that. It's not just about the ventricles, right? Dr Cutsforth-Gregory: That's exactly right. So, we think hydrocephalus, that means ventriculomegaly, and it does, but DESH, as you said, the mouthful “disproportionately enlarged subarachnoid space hydrocephalus”, is basically CSF accumulation around the brain outside the ventricles. Common features would be enlarged Sylvian fissures, focally dilated sulci, and then at the same time, up high on the convexity, tight sulci. So, it's this combination; there's clearly a flow problem where CSF is being trapped in certain areas outside the brain and excluded from others. And that is a common feature. And that alone predicts a positive response to shunt surgery. Dr Jones: I remember the first time one of my colleagues pointed that out to me on an image, and it just made me wonder how many times I had missed it before that point in my career. But that's the point, is to learn and move forward. One of the common themes, I think, in this practice, one of the common themes in this issue, is the interdisciplinary work that's necessary not just for treating patients with CSF dynamics disorders, but also the diagnosis. We really do have to work carefully and closely with neurosurgeons and with radiologists. And to reflect that we had a pretty diverse group of authors. Moreso, I think, that we usually do for Continuum, given the overlap with the radiology and surgical practice. As you were reviewing these articles, were there any unique or distinctive perspectives that you saw come through? Dr Cutsforth-Gregory: Absolutely. And I have to say, I'm so proud of the diverse author panel we were able to put together: as you said, including clinicians, but also neuroradiologists; neurosurgeons, both adult and pediatric; as well as a couple- an ENT surgeon to talk about those cranial skull base leaks. So, we really brought together what we think is necessary to take care of these patients. As far as unique perspectives here, I would point to the article on diagnosis, surgical treatment, the long term implications of atraumatic cranial CSF leaks. So, these are the patients who present with CSF otorrhea or rhinorrhea and do not have a history of skull base surgery or trauma to explain it. That is often a chronic intracranial hypertension patient who, instead of staying sealed up and building up pressure and presenting with papilledema and headaches, had a leak. And that's relevant because, after it’s fixed, that patient needs to come to us in neurology to be monitoring for papilledema, measure lumbar puncture, open pressure. And we've developed that as part of our workflow with our colleagues in neurosurgery and ENT who seal those leaks, because that's a patient who is at high risk of recurrent leak if we don't treat the underlying high pressure disorder. That's a new concept, I think, for many of us. And so, to be able to put that front and center in an article, in an issue for practicing neurologists, I think, is really important, and it's something we haven't been able to do before. Similarly, the article by Dr Olga Fermo on the treatment of persistent symptoms after normalization of CSF pressure. We've all taken care of patients who had a CSF leak or had hypertension, and it seems like those issues are resolved, and yet they still have headaches. The IIH treatment trial taught us that that happens in perhaps two thirds of patients with IIH. And so, to have Dr Fermo's article on how to help those patients manage the headaches when the CSF disorder seems to have been resolved, I think it's super useful. The last one I would mention is just the final one by Dr Shenandoah Robinson, a pediatric neurosurgeon, talking about child onset hydrocephalus. And so, NPH is the focus of most of those other articles. But the patients who we will take care of as adult neurologists, child neurologists, whose issue really started early on, it’s important that we stay involved and how to do that, what things we should be watching for, when to suspect shunt malfunction, it’s all covered in Dr Robinson's article, and it’s a unique one for this issue. Dr Jones: It's always interesting to read articles, as a neurologist, that are written by a neurosurgeon because, you know, they have a different perspective, right? T're intervening on the anatomy, and just hearing how they think about these things was illuminating for me. The article on atraumatic cranial skull base CSF leaks, that connection with intracranial hypertension, I was unaware of that. So that was a good learning point for me. And while we're still on the too-high-pressure problem of idiopathic intracranial hypertension, do we have any more insight into what causes that? What's the mechanism of that disease? Do we know any more than we used to? Dr Cutsforth-Gregory: We know more than we used to. We certainly don't understand all of it. But rather than just a disease of reproductive-age women carrying extra weight, it is now recognized as, really, a metabolic and hormonal-driven condition. And it's relevant because it really highlights new ways to intervene and to treat these patients. The GLP-1 inhibitors may have a role, considering some of the comorbidities like polycystic ovary syndrome and the hormonal connections. The patients who perhaps are female-to-male trans, who then can present with intranial hypertension, and how we can help them without needing to take them off gender confirming hormone therapy, is all really relevant to help us help more patients by having that broader understanding of the cause of disease, that it’s not just weight gain/weight loss. Dr Jones: Fantastic, and very useful to know. Thinking of the other end of the spectrum, right, rather than too much CSF or too much CSF pressure… I know this has been a focus of your academic work, Dr Cutsforth-Gregory. We also have disorders of CSF hypotension where the pressure is too low, and that this is usually reflective of a dural defect. I know in my own practice, sometimes, these are very difficult to find, and that's really- as you said, diagnosis is the first step, but then we have to find the problem and try to direct surgeons where to go to repair it. Do you have any tips for our listeners on how to approach the hunt for the source of CSF leaks? Dr Cutsforth-Gregory: Absolutely. And I first have to give a call out to my mentor, Dr Bahram Mokri, who is the one who first reported the diffuse sterile enhancement, back in the early 1990s, that marks some, but not all, patients with spontaneous intracranial hypotension. He would also remind me that that's not a good term to call it, even though I just did and I will continue to do it intermittently. Because really, this is an underlying spinal CSF leak or a CSF venous fistula. And the problem is not too-low pressure, which is why hypotension is probably not the best word, but too-low volume. It's intracranial CSF hypovolemia. You know, with the opportunity that Dr Mokri gave me to see some of those patients with him and become intrigued by it, it is the bulk of my clinical practice, my research focus, and the conversations I get to have every single day with neuroradiologists and neurosurgeons. I tell patients, it is a field that is moving incredibly quickly and that, when I see them again in a few months or the next year, for whatever reason, I always joke and I say, I reserve the right to have different recommendations, because it is moving. I finished residency in 2014, which is the year CSF fistulas were first reported. I'm sure they existed before that. So, it was a lack of awareness. And so, look for what you know. Now we know to look for fistulas. You find what you look for; we've developed a number of new myographic techniques to find these things, and they are now the majority of the type of leak that we find. So, it is a patient population where we were missing more than we were hitting ten years ago. And now maybe that's still true, but we're certainly finding a lot more than we used to because of those collaborations. Dr Jones: Thinking back to DESH, right? Once you're aware that it is something that can be identified, you start to see it more and more. And again, that's how we move the field forward. And again, the CSF venous fistula story is one that I know was relatively new to me and something I learned a lot about reading through the issue. And hopefully our readers and our listeners find some insights and benefits there. This is a rapidly changing field. This may be a hard question to answer, but when you look into the future, what are some of the changes on the horizon in this practice? Dr Cutsforth-Gregory: See, I'll probably point to the- both diagnosis and treatment. We're recognizing that it's, like I said earlier, not all orthostatic headache, but some of the other manifestations, such as frontotemporal brain sagging syndrome, can be a manifestation of leak. So, suspected leak is the first step. Then you have to look for it. And MRI will change, you know, incrementally, I'm sure; we'll get higher resolution pictures. But the C wave of change is going to be in how to do the myelogram, what imaging modality we use; and the newest kit on the block, if you will, is photon-counting detector CT myelography. That's a different kind of CT scanner than we've been used to over the last few decades. It detects light energy differently. It allows better signal-to-noise ratio, faster acquisition of scans. And so, using that allows us to get thinner slices through the spine to look for leaks and fistulas. I think photon CT will become more widespread because it has applications well beyond neurology and just myelograms. And so, as those scanners become more available, everyone will get to be better at finding these leaks. And then treatment, I'll highlight a procedure called transvenous paraspinal vein embolization. You know, a CSF venous fistula is an abnormal connection between a nerve root sleeve and a vein. And the CSF is escaping up through the that vein in an unregulated fashion. And historically when those were found, the treatment was to ligate the nerve root. Get rid of the nerve root sleeve, you get rid of the abnormal connection, you get rid of the vein, you stop the leak. And that is effective. A number of studies have shown that. But it's also invasive; it requires a laminectomy and losing a nerve root. You can't do that at every level of the spine, right? This is predominantly thoracic, and only if you're away from the artery of Adamkiewicz. But a few years ago, Dr Walid Benjigchi pioneered a procedure of going through the vein and embolizing it, putting in a liquid embolic agent that seals it off. The nerve root stays attacked. We can do it at every level of the spine, and it's an outpatient, endovascular procedure to fix fistulas. That kind of minimally invasive procedure for fistulas has been a major shift away from the open surgeries. We will, I think, make advances with new catheters and new needles to be able to do some other kind of minimally invasive procedures for the other kinds of leaks. I think that's what we'll be seeing, is less and less invasive procedures on the leak side. Dr Jones: Great summary there. Thank you. So, it sounds like a combination of hopefully improved clinician awareness, which will improve diagnostic recognition; more sensitive tools like the photon counting CTS; and less invasive definitive therapies, which I think is promising for the field. And you've led a lot of that work, Dr Cutsforth-Gregory, over the last few years. When you see these patients, I'm sure it's rewarding to see patients with previously poorly-recognized or misunderstood symptoms get better. Is that the most rewarding part of this practice for you, or what can you tell me about your experience in the care of these patients? Dr Cutsforth-Gregory: You know, I'm a curious person. I like to learn. So, I will say it is really rewarding to develop a new technique and put it into practice and see it increase our hit rate on finding these leaks and helping these patients. But nothing beats the feeling of taking a patient who's been stuck in bed or saying that they can't function and they're out of work or out of their family life, and getting that Christmas card or that hug that says they're back. But, you know, we're here to help our patients, and nothing can beat that feeling. Dr Jones: I think that's a great point to end on. Dr Cutsforth-Gregory, thank you for joining us. Thank you for such a detailed discussion of a broad, diverse topic. I learned a lot today---some things that I wasn't aware of, having read the issue---and hopefully our listeners did, too. Dr Cutsforth-Gregory: Thank you so much, Dr Jones. Dr Jones: Again, we've been speaking with Dr Jeremy Cutsforth-Gregory, Guest Editor of Continuum's first-ever issue focusing on CSF dynamics. Please check it out. And thank you... /episode/index/show/continuumjournal/id/36660305

BONUS EPISODE: Clinical Applications of Artificial Intelligence in Neurology Practice With Dr. Peter Hadar 05/24/2025

BONUS EPISODE: Clinical Applications of Artificial Intelligence in Neurology Practice With Dr. Peter Hadar As artificial intelligence (AI) tools become increasingly mainstream, they can potentially transform neurology clinical practice by improving patient care and reducing clinician workload. Critically evaluating these AI tools for clinical practice is important for successful implementation. In this episode, Katie Grouse, MD, FAAN speaks with Peter Hadar, MD, MS, coauthor of the article “Clinical Applications of Artificial Intelligence in Neurology Practice” in the Continuum® April 2025 Neuro-ophthalmology issue. Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California. Dr. Hadar is an instructor of neurology at Harvard Medical School and an attending physician at the Massachusetts General Hospital in Boston, Massachusetts. Additional Resources Read the article: Subscribe to Continuum®: Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Guest: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about subscribing to the journal, listening to verbatim recordings of the articles, and exclusive access to interviews not featured on the podcast. Dr Grouse: This is Dr Katie Grouse. Today I'm interviewing Dr Peter Hadar about his article on clinical applications of artificial intelligence in neurology practice, which he wrote with Dr Lydia Moura. This article appears in the April 2025 Continuum issue on neuro-ophthalmology. Welcome to the podcast, and please introduce yourself to our audience. Dr Hadar: Hi, thanks for having me on, Katie. My name is Dr Peter Hadar. I'm currently an instructor over at Mass General Hospital, Harvard Medical School, and I'm excited to talk more about AI and how it's going to change our world, hopefully for the better. Dr Grouse: We're so excited to have you. The application of AI in clinical practice is such an exciting and rapidly developing topic, and I'm so pleased to have you here to talk about your article, which I found to be absolutely fascinating. To start, I'd like to hear what you hope will be the key takeaway from your article with our listeners. Dr Hadar: Yeah, thank you. The main point of the article is that AI in medicine is a tool. It's a wonderful tool that we should be cautiously optimistic about. But the important thing is for doctors, providers to be advocates on their behalf and on behalf of their patients for the appropriate use of this tool, because there are promises and pitfalls just with any tool. And I think in the article we detail a couple ways that it can be used in diagnostics, in clinical documentation, in the workflow, all ways that can really help providers. But sometimes the devil is in the details. So, we get into that as well. Dr Grouse: How did you become interested in AI and its application, specifically in the practice of neurology? Dr Hadar: When I was a kid, as most neurologists are, I was- I nerded out on a lot of sci-fi books, and I was really into Isaac Asimov and some of his robotics, which kind of talks about the philosophy of AI and how AI will be integrated in the future. As I got into neurology, I started doing research neurology and a lot of folks, if you're familiar with AI and machine learning, statistics can overlap a lot with machine learning. So slowly but surely, I started using statistical methods, machine learning methods, in some of my neurology research and kind of what brought me to where I am today. Dr Grouse: And thinking about and talking about AI, could you briefly summarize a few important terms that we might be talking about, such as artificial intelligence, generative AI, machine learning, etcetera? Dr Hadar: It's a little difficult, because some of these terms are nebulous and some of these terms are used in the lay public differently than other folks would use it. But in general, artificial intelligence is kind of the ability of machines or computers to communicate independently. It’s similar to as humans would do so. And there are kind of different levels of AI. There's this very hard AI where people are worried about with kind of terminator-full ability to replicate a human, effectively. And there are other forms of narrow AI, which are actually more of what we're talking about today, and where it's very kind of specific, task-based applications of machine learning in which even if it's very complex, the AI tools, the machine learning tools are able to give you a result. And just some other terms, I guess out there. You hear a lot about generative AI. There's a lot of these companies and different algorithms that incorporate generative AI, and that usually kind of creates something, kind of from scratch, based on a lot of data. So, it can create pictures, it can create new text if you just ask it. Other terms that can be used are natural language processing, which is a big part of some of the hospital records. When AI tools read hospital records and can summarize something, if it can translate things. So, it turns human speech into these results that you look for. And I guess other terms like large language models are something that also have come into prominence and they rely a lot on natural language processing, being able to understand human speech, interpret it and come up with the results that you want. Dr Grouse: Thank you, that's really helpful. Building on that, what are some of the current clinical applications of AI that we may already be using in our neurologic practice and may not even be aware that that's what that is? Dr Hadar: It depends on which medical record system you use, but a very common one are some of the clinical alerts that people might get, although some of them are pretty basic and they can say, you know, if the sodium is this level, you get an alert. But sometimes they do incorporate fancier machine learning tools to say, here's a red flag. You really should think about contacting the patient about this. And we can talk about it as well. It might encourage burnout with all the different flags. So, it's not a perfect tool. But these sorts of things, typically in the setting of alerts, are the most common use. Sorry, and another one is in folks who do stroke, there are a lot of stroke algorithms with imaging that can help detect where the strokes occur. And that's a heavy machine learning field of image processing, image analysis for rapid detection of stroke. Dr Grouse: That's really interesting. I think my understanding is that AI has been used specifically for radiology interpretation applications for some time now. Is that right? Dr Hadar: In some ways. Actually, my background is in neuroimaging analysis, and we've been doing a lot of it. I've been doing it for years. There's still a lot of room to go, but it's really getting there in some ways. My suspicion is that in the coming years, it’s going to be similar to how anesthesiologists at one point were actively bagging people in the fifties, and then you develop machines that can kind of do it for you. At some point there's going to be a prelim radiology read that is not just done by the resident or fellow, but is done by the machine. And then another radiologist would double check it and make sure. And I think that's going to happen in our lifetime. Dr Grouse: Wow, that's absolutely fascinating. What are some potential applications of AI in neurologic practice that may be most high-yield to improve patient care, patient access, and even reduce physician burnout? Dr Hadar: These are separate sort of questions, but they're all sort of interlinked. I think one of the big aspects of patient care in the last few years, especially with the electronic medical record, is patients have become much more their own advocates and we focus a lot more on patient autonomy. So, they are reaching out to providers outside of appointments. This can kind of lead to physician burnout. You have to answer all these messages through the electronic medical record. And so having, effectively, digital twins of yourself, AI version of yourself, that can answer the questions for the patient on your off times is one of the things that can definitely help with patient care. In terms of access, I think another aspect is having integrated workflows. So, being able to schedule patients efficiently, effectively, where more difficult patients automatically get one-hour appointments, patients who have fewer medical difficulties might get shorter appointments. That's another big improvement. Then finally, in terms of physician burnout, having ambient intelligence where notes can be written on your behalf and you just need to double-check them after allows you to really have a much better relationship with the patients. You can actually talk with them one on one and just focus on kind of the holistic care of the patient. And I think that's- being less of a cog in the machine and focusing on your role as a healer would be actually very helpful with the implementation of some of these AI tools. Dr Grouse: You mentioned ambient technology and specifically ambient documentation. And certainly, this is an area that I feel a lot of excitement about from many physicians, a lot of anticipation to be able to have access to this technology. And you mentioned already some of the potential benefits. What are some of the potential… the big wins, but then also potential drawbacks of ambient documentation? Dr Hadar: Just to kind of summarize, the ambient intelligence idea is using kind of an environmental AI system that, without being very obtrusive, just is able to record, able to detect language and process it, usually into notes. So, effectively like an AI scribe that is not actually in the appointment. So, the clear one is that---and I've seen this as well in my practice---it's very difficult to really engage with the patient and truly listen to what they're saying and form that relationship when you're behind a computer and behind a desk. And having that one-on-one interaction where you just focus on the patient, learn everything, and basically someone else takes notes for you is a very helpful component of it. Some of the drawbacks, though, some of it has to do with the existing technology. It's still not at the stage where it can do everything. It can have errors in writing down the medication, writing down the exact doses. It can't really, at this point, detect some of the apprehensions and some of the nonverbal cues that patients and providers may kind of state. Then there's also the big one where a lot of these are still done by startups and other companies where privacy may be an issue, and a lot of patients may feel very uncomfortable with having ambient intelligence tools introduced into their clinical visit, having a machine basically come between the doctor and the patient. But I think that over time these apprehensions will lessen. A lot of the security will improve and be strengthened, and I think that it's going to be incorporated a lot more into clinical practice. Dr Grouse: Yeah, well, we'll all be really excited to see how that technology develops. It certainly seems like it has a lot of promise. You mentioned in your article a lot about how AI can be used to improve screening for patients for certain types of conditions, and that certainly seems like an obvious win. But as I was reading the article, I couldn't help but worry that, at least in the short term, these tools could translate into more work for busy neurologists and more demand for access, which is, you know, already, you know, big problems in our field. How can tools like these, such as, like, for instance, the AI fundoscopic screening for vascular cognitive risk factors help without adding to these existing burdens? Dr Hadar: It's a very good point. And I think it's one of the central points of why we wanted to write the article is that these AI in medicine, it's, it's a tool like any other. And just like when the electronic medical record came into being, a lot of folks thought that this was going to save a lot of time. And you know, some people would say that it actually worsened things in a way. And when you use these diagnostic screening tools, there is an improvement in efficiency, there is an improvement in patient care. But it's important that doctors, patients advocate for this to be value-based and not revenue-based, necessarily. And it doesn't mean that suddenly the appointments are shorter, that now physicians have to see twice as many patients and then patients just have less of a relationship with their provider. So, it's important to just be able to integrate these tools in an appropriate way in which the provider and the patient both benefit. Dr Grouse: You mentioned earlier about the digital twin. Certainly, in your article you mentioned, you know, that idea along with the idea of the potential of development of virtual chatbot visits or in-person visits with a robot neurologist. And I read all this with equal parts, I think excitement, but horror and and fear. Can you tell us more about what these concepts are, and how far are we from seeing technology like this in our clinics, and maybe even, what are the risks we need to be thinking about with these? Dr Hadar: Yeah. So, I mean, I definitely think that we will see implementation of some of these tools in our lifetime. I'm not sure if we're going to have a full walking, talking robot doing some of the clinical visits. But I do think that, especially as we start doing a lot more virtual visits, it is very easy to imagine that there will be some sort of video AI doctor that can serve as, effectively, a digital twin of me or someone else, that can see patients and diagnose them. The idea behind the digital twin is that it's kind of like an AI version of yourself. So, while you only see one patient, an AI twin can go and see two or three other patients. They could also, if the patients send you messages, can respond to those messages in a way that you would, based on your training and that sort of thing. So, it allows for the ability to be in multiple places at once. One of the risks of this is, I guess, overreliance on the technology, where if you just say, we're just going to have a chatbot do everything for us and then not look at the results, you really run the risk of the chatbot just recommending really bad things. And there is training to be had. Maybe in fifty years the chatbot will be at the same level as a physician, but there's still a lot of room for improvement. I personally, I think that my suspicion as to where things will go are for very simple visits in the future and in our lifetime. If someone is having a cold or something like that and it goes to their primary care physician, a chatbot or something like that may be of really beneficial use. And it'll help segment out the different groups of simple diagnosis, simple treatments can be seen by these robots, these AI, these machine learning tools; and some of the more complex ones, at least for the early implementation of this will be seen by more specialized providers like neurologists and subspecialist neurologists too. Dr Grouse: That certainly seems reasonable, and it does seem that the more simple algorithmic things are always where these technologies will start, but it'll be interesting to see where things can go with more complex areas. Now I wanted to switch gears a little bit in the article- and I thought this was really important because I see it as being certainly one of the bigger drawbacks of AI, is that despite the many benefits of artificial intelligence, AI can unfortunately perpetuate systemic bias. And I'm wondering if you could tell us a little bit more about how this happened? Dr Hadar: I know I'm beating a dead horse on this, but AI is a tool like any other. And the problem with it is that what you put in is very similar to what you get out. And there's this idea in computer science of “garbage in, garbage out”. If you include a lot of data that has a lot of systemic biases already in the data, you're going to get results that perpetuate these things. So, for instance, if in dermatologic practices, if you just had a data set that included people of one skin color or one race and you attempted to train a model that would be able to detect skin cancer lesions, that model may not be easily applicable to people of other races, other ethnicities, other skin colors. And that can be very damaging for care. And it can actually really, really hurt the treatments for a lot of the patients. So that is one of the, kind of, main components of the systemic biases in AI. The way we mitigate them is by being aware of it and actually implementing, I guess, really hard stops on a lot of these tools before they get into practice. Being sure, did your data set include this breakdown of sex and gender, of race and ethnicity? So that the stuff you have in the AI tool is not just a very narrow, focused application, but can be generalized to a large population, not just of one community, one ethnic group, racial group, one country, but can really be generalized throughout the world for many patients. Dr Grouse: The first step is being aware of it, and hopefully these models will be built thoughtfully to help mitigate this as much as possible. I wanted to ask as well, another concern about AI is the safety of private data. And I'm wondering, as we're starting to do things like use ambient documentation, AI scribe, and other types of technologies like this, what can we tell our patients who are concerned about the safety of their personal data collected via these programs, particularly when they're being stored or used with outside companies that aren't even in our own electronic medical records system? Dr Hadar: Yeah, it's a very good question, and I think it's one of the major limitations of the current implementation of AI into clinical practice, because we still don't really have great standards---medical standards, at least---for storing this data, how to analyze this data. And my suspicion is that at some point in the future, we're going to need to have a HIPAA compliance that's going to be updated for the 21st century, that will incorporate the appropriate use of these tools, the appropriate use of these data storage, of data storage beyond just PHI. Because there's a lot more that goes into it. I would say that the important thing for how to implement this, and for patients to be aware of, is being very clear and very open with informed consent. If you're using a company that isn't really transparent about their data security and their data sharing practices, that needs to be clearly stated to the patient. If their data is going to be shared with other people, reanalyzed in a different way, many patients will potentially consider not participating in an AI implementation in clinic. And I think the other key thing is that this should be, at least initially, an opt-in approach as opposed to an opt-out approach. So patients really have- can really decide and have an informed opinion about whether or not they want to participate in the AI implementation in medicine. Dr Grouse: Well, thank you so much for explaining that. And it does certainly sound like there's a lot of development that's going to happen in that space as we are learning more about this and the use of it becomes more prevalent. Now, I also wanted to ask, another good point that you made in your article---and I don't think comes up enough in this area, but likely will as we're using it more---AI has a cost, and some of that cost is just the high amount of data and computational processing needed to use it, as well as the effects on the... /episode/index/show/continuumjournal/id/35872630

Symptomatic Treatment of Neuro-ophthalmic Visual Disturbances With Dr. Sachin Kedar 05/21/2025

Symptomatic Treatment of Neuro-ophthalmic Visual Disturbances With Dr. Sachin Kedar Neuro-ophthalmic deficits significantly impair quality of life by limiting participation in employment, educational, and recreational activities. Low-vision occupational therapy can improve cognition and mental health by helping patients adjust to visual disturbances. In this episode, Katie Grouse, MD, FAAN, speaks with Sachin Kedar, MD, FAAN, author of the article “Symptomatic Treatment of Neuro-ophthalmic Visual Disturbances” in the Continuum® April 2025 Neuro-ophthalmology issue. Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California. Dr. Kedar is the Cyrus H Stoner professor of ophthalmology and a professor of neurology at Emory University School of Medicine in Atlanta, Georgia. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Guest: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Grouse: This is Dr Katie Grouse. Today I'm interviewing Dr Sachin Kedar about his article on symptomatic treatment of neuro-ophthalmic visual disturbances, which appears in the April 2025 Continuum issue on neuro-ophthalmology. Welcome to the podcast, and please introduce yourself to our audience. Dr Kedar: Thank you, Katie. This is Sachin Kedar. I'm a neuro-ophthalmologist at Emory University, and I've been doing this for more than fifteen years now. I trained in both neurology and ophthalmology, with a fellowship in neuro-ophthalmology in between. It's a pleasure to be here. Dr Grouse: Well, we are so happy to have you, and I'm just so excited to be discussing this article with you, which I found to be a real treasure trove of useful clinical information on a topic that many find isn't covered enough in their neurologic training. I strongly recommend all of our listeners who work with patients with visual disturbances to check this out. I wanted to start by asking you what you hope will be the main takeaway from this article for our listeners? Dr Kedar: The most important takeaway from this article is, just keep vision on your radar when you are evaluating your patients with neurological disorders. Have a list of a few symptoms, do a basic screening vision, and ask patients about how their vision is impacting the quality of life. Things like activities of daily living, hobbies, whether they can cook, dress, ambulate, drive, read, interact with others. It is very important for us to do so because vision can be impacted by a lot of neurological diseases. Dr Grouse: What in the article do you think would come as the biggest surprise to our listeners? Dr Kedar: The fact that impairment of vision can magnify and amplify neurological deficits in a lot of what we think of as core neurological disorders should come as a surprise to most of the audience. Dr Grouse: On that note, I think it's probably helpful if you could remind us about the types of visual disturbances we should be thinking about and screening for in our patients? Dr Kedar: Patients who have neurological diseases can have a whole host of visual deficits. The simplest ones are deficits of central vision. They can have problems with their visual field. They can have abnormalities of color vision or even contrast sensitivity. A lot of our patients also complain of light sensitivity, eyes feeling tired when they're doing their usual stuff. Some of our patients can have double vision, they can have shaky vision, which leads to their sense of imbalance and maybe a fall risk to them. Dr Grouse: It's really helpful to think about all the different aspects in which vision can be affected, not just sort of the classic loss of vision. Now, your article also serves as a really important reminder, which you alluded to earlier, about how impactful visual disturbances can be on daily activities. Could you elaborate a little further on this, and particularly the various domains that can be affected when there are visual disturbances present? Dr Kedar: So, when I look at how visual disturbances affect quality of life, I look at two broad categories. One is activities of basic daily living. These would be things like, are you able to cook? Are you able to ambulate not just in your home, but in your neighborhood? Are you able to drive to your doctor's appointment or to visit with your family? Are you able to dress yourself appropriately? Are you able to visualize the clothing and choose them appropriately? And then the second category is recreational activities. Are you able to read? Are you able to watch television? Are you able to visit the theatre? Are you able to travel? Are you able to participate in group activities, be it with your family or be it with your social group? It is very important for us to ask our patients if they have problems doing any of this because it really can adversely impact the quality of life. Dr Grouse: I think, certainly with all the things we try to get through talking with our patients, this may not be something that we do spend a lot of time on. So, I think it's it is a good reminder that when we can, being able to ask about these are going to be really important and help us hit on a lot of other things we may not even realize or know to ask about. Now, I was really struck when I was reading your article by the meta-analysis that you had quoted that had showed 47% higher risk of developing dementia among the visually impaired compared to those without visual impairments. Should we be doing more in-depth visual testing on all of our patients with cognitive symptoms? Dr Kedar: This is actually the most interesting part of this article, and kind of hones in on the importance of vision in neurological disorders. Now I want to clarify that patients with visual disorders, it's not a causative influence on dementia, but if you have a patient with an underlying cognitive disorder, any kind of visual disturbance will significantly make it worse. And this has been shown in several studies, both in the neurologic and in the ophthalmological literature. So, I quoted one of the big meta-analysis over there, but studies have clearly shown that if you have these patients and treat them for their visual deficits, their cognitive indices can actually significantly improve. To answer your question, I would say a neurologist should include basic vision screening as part of every single evaluation. Now, I know it's a hard thing in, you know, these days when we are literally running on the hamster wheel, but I can assure you that it won't take you more than 2 to 3 minutes of your time to do this basic screening; in fact, you can have one of your assistants included as part of the vital signs assessment. What are these basic screening tools? Measure the visual acuity for both near and distance. Check and see if their visual field’s off with the confrontation. Look at their eye movements. Are they able to move their eyes in all directions? Are the eyes stable when they're trying to fixate on a particular point? I think if you can do these basic things, you will have achieved quite a bit. Dr Grouse: That's really helpful, and thanks for going through some of the standard, or really, you know, solid basic foundation of visual testing we should be thinking about doing. I wanted to move on to some more details about the visual disturbances. You made an excellent point that there are many types of primary ophthalmologic conditions that can cause visual disturbances that we should keep in mind. So maybe not things that we think about a lot on a day-to-day basis, but, you know, are still there and very common. What are some of the most common ones, and when should we be referring them to see an ophthalmologist? Dr Kedar: So, it depends on the age group of your patient population. Now, the majority of us are adult neurologists, and so the kinds of ophthalmic conditions that we see in this population is going to be different from the pediatric age group. So in the adult population, we might see patients with uncorrected refractive error, presbyopia, patients who have cataracts creep on them, they may have glaucoma, they may have macular degeneration, and these tend to have a slightly higher incidence in the older age group. Now for those of us who are taking care of the younger population, uncorrected refractive errors, strabismus and amblyopia tend to be fairly common causes of visual deprivation in this age group. What I would encourage all of our neurologists is, make sure that your patients get a basic eye examination at least once a year. Just like you want them to go to their primary care and get an annual maintenance visit, everybody should go to the ophthalmologist or the optometrist and get a basic examination. And, if you're resourceful enough, have your patients bring a copy of that assessment. Whether it is normal or there's some abnormality, it is going to help you in the management. Dr Grouse: Absolutely. I think that's a great piece of advice, to think of it almost, like, them seeing their primary care doctor, which of course we offer encourage our patients to do, thinking of this as another very important piece of standard primary care. If a patient comes to you reporting difficulty reading due to possible visual disturbances, I'm curious, can you walk us through how you would approach this evaluation? Dr Kedar: It is not a very common presenting complaint of our patients, even in the neuro-ophthalmology clinic. It's a very rare patient that I see who comes and says, I cannot read or, I have difficulty reading. Most of the patients will come saying, oh, I cannot see. And then you have to dig in to find out, what does that actually mean? What can you not see? Is it a problem in your driving? Is it a problem in your reading? Or is it a problem that occurs at all times? Now you asked me, how do you approach this evaluation? One of the things that all of us, whether we are neurologists, ophthalmologists, or neuro-ophthalmologists, forget to do is to actually have the patient read a paragraph, a sentence, when they are in clinic. And that will give you a lot of ideas about what might actually be going wrong with the patient. Now, as far as how do I approach this evaluation, I will do a basic screening examination to make sure that their visual acuity is good for both distance and near. A lot of us tend to do either distance or near and we will miss the other parameter. You want to do a basic confrontation visual field to make sure that they do not have any subtle deficits that's impacting their ability to read. Examine the eye movements, do a fundoscopic examination. Now, once you've done this basic screening, as a neurologist, you already have some idea of whether your patient has a lesion along the visual pathways. If you suspect that this is a problem with, say, the visual pathways, ask your ophthalmology colleague to do a formal visual field assessment, and that'll pick up subtle deficits of central visual field. And lastly, don't forget higher visual function testing or cortical visual function testing. So basically, you're looking for neglect, phenomenon, or simultanagnosia, all of which tends to have an impact on reading. So, in the manuscript I have a schema of how you can approach a patient with reading difficulties, and in that ischemia you will see categories of where things can go wrong during the process of reading. And if you can approach your patient systematically through one of those domains, there's a fairly good chance that you'll be able to pick up a problem. Dr Grouse: Going a little further on to when you do identify problems with loss of central or peripheral vision, what are some strategies for symptomatic management of these types of visual disturbances? Dr Kedar: As a neurologist, if you pick up a problem with the vision, you have to send this patient to an eye care provider. The vast majority of people who have visual disturbances, it’s from an eye disease. You know, as I alluded to earlier, it can be something as simple as uncorrected refractive error, and that can be fixed easily. A lot of patients in our older age group will have dry eye syndrome, which means they are unable to adequately lubricate the surface of the eye, and as a result, it degrades the quality of their vision. So, they tend to get intermittent episodes of blurred vision, or they tend to get glare. They tend to get various forms of optical aberration. Patients can have cataracts, patients can have glaucoma or macular degeneration. And in all of those instances, the goal is to treat the underlying disease, optimize the vision, and then see what the residual deficit is. By and large, if a patient has a problem with the central vision, then magnification will help them for activities that they perform at near; say, reading. Now for patients with peripheral vision problem, it's a different entity altogether. Again, once you've identified what the underlying cause is, your first goal is to treat it. So, for example, if your patient has glaucoma, which is affecting peripheral vision, you're going to treat glaucoma to make sure that the visual field does not progress. Now a lot of what happens after that is rehabilitation, and that is always geared towards the specific activities that are affected. Is it reading? Is it ambulating? Is it watching television? Is it driving? And then you can advise as a neurologist, you can advise your occupational therapist or low vision specialist and say, hey, my patient is not able to do this particular activity. Can we help them? Dr Grouse: Moving on from that, I wanted to also hit on your approach when patients have disorders of ocular motility. What are some things you can do for symptomatic management of that? Dr Kedar: So, patients with ocular motility can have two separate symptoms. Two, you know, two disabling symptoms, as they would call it. One is double vision and the other is oscillopsia, or the feeling or the visualization of the environment moving in response to your eyes not being able to stay still. Typically, you would see this in nystagmus. Now, let's start with diplopia. Diplopia is a fairly common presenting complaint for neurologists, ophthalmologists, and the neuro-ophthalmologist. The first aspect in the management of diplopia is to differentiate between monocular diplopia and binocular diplopia. Now, monocular diplopia is when the double vision persists even after covering one eye. And that is never a neurological issue. It's almost always an ophthalmic problem, which means the patient will then have to be assessed by an eye care provider to identify what's causing it. And again, refractive error, cataracts, opacities, they can do it. Now, if the patient is able to see single vision by covering one eye at a time, that's binocular diplopia. Now, in patients with binocular diplopia in the very early stages of the disease, the standard treatment regimen is just monocular occlusion. Cover one eye, the diplopia goes away, and then give it time to improve on its own. So, this is what we would typically do in a patient with, say, acute sixth nerve palsy or fourth nerve palsy or third nerve palsy, maybe expect spontaneous improvement in a few months. Now if the double vision does not improve and persists long term, then the neuro-ophthalmologist or the ophthalmologist will monitor the amount of deviation to see if it fluctuates or if it stays the same. So, what are the treatment options that we have in a patient who absolutely refuses any intervention or is not a candidate for any intervention? Monocular occlusion still remains the viable option. Now, patients who have stable ocular deviation can benefit from using prisms in their glasses, or they can be sent to a surgeon to have a strabismus surgery that can realign their eyes. So, again, a broad answer, but there are options available that we can use. Dr Grouse: Thank you for that overview. I think that's just really helpful to keep in mind as we're working with these patients and thinking about what their options are. And then finally, I wanted to touch on patients with higher-order vision processing and attention difficulties. What are some strategies for them? Dr Kedar: These are frankly the most difficult patients that I get to manage in my clinic, simply because there is no effective therapies for managing them. In fact, I think neurologists are far better at this than ophthalmologists or even neuro-ophthalmologists. In patients with attentional disorders, everything boils down to the underlying cause, whether you can treat it or whether it is a slowly progressive, you know, condition, such as from neurodegenerative diseases. And that tailors our goals towards therapy. The primary goal is for safety. A lot of these patients who have visual disturbances from vision processing or attention, they are at accident and fall risk. They have problems with social interactions. And, importantly, there is a gap of understanding of what's going on, not just from their side but also from the family’s side. So, I tend to approach these patients from a safety perspective and social interaction perspective. Now, I have a table listed in the manuscript which will go into details of what the specific things are. But in a nutshell, if your patient has neglect in a specific part of the visual field, they have accident risk on that side. Simple things like walking through a doorway, they can hurt their shoulders or their knees when they bang into the wall on that side because they are unable to judge what's on the other side. Another example would be a patient who has simultanagnosia or a downgaze policy, such as from progressive super nuclear policy. They are unable to look down fast enough, or they are simply unable to look down and appreciate things that are on the floor, and so they can trip and fall. Walking downstairs is also not a huge risk because they are unable to judge distances as they walk down. A lot of what we see in these patients are things that we have to advise occupational therapists and help them improve these safety parameters at home. Another thing that we often forget is patients can inadvertently cause a social incident when they tend to ignore people on their affected side. So, if there is a family gathering, they tend to consistently ignore a group of people who are sitting on the affected side as opposed to the other side. And I've had more than a few patients who've come and said that, I may have offended some of my friends and family. In those instances, it's always helpful when they are in clinic to demonstrate to the family how this can be awkward and how this can be mitigated. So, having everybody sit on one side is a useful strategy. Advise your family and friends before a gathering that, hey, this may happen. And it is not because it is deliberate, but it's because of the medical condition. And that goes a lot, you know, further in helping our patients come out of social isolation because they are also afraid of offending people, you know. And they can also participate socially, and it can overall improve their quality of life. Dr Grouse: That's a really helpful tip, and something I'll keep in mind with my patients with neglect and visual field cuts. Thank you so much for coming to talk with us today. Your article has been so helpful, and I urge everybody listening today to take a look. Dr Kedar: Thank you, Katie. It was wonderful talking to you. Dr Grouse: I've been... /episode/index/show/continuumjournal/id/35872555

Supranuclear Disorders of Eye Movements With Dr. Gregory Van Stavern 05/14/2025

Supranuclear Disorders of Eye Movements With Dr. Gregory Van Stavern Dysfunction of the supranuclear ocular motor pathways typically causes highly localizable deficits. With sophisticated neuroimaging, it is critical to better understand structure-function relationships and precisely localize pathology within the brain. In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Gregory P. Van Stavern, MD, author of the article “Supranuclear Disorders of Eye Movements” in the Continuum® April 2025 Neuro-ophthalmology issue. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Van Stavern is the Robert C. Drews professor of ophthalmology and visual sciences at Washington University in St Louis, Missouri. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today I'm interviewing Dr Gregory Van Stavern, who recently authored an article on intranuclear and supranuclear disorders of eye movements for our latest Continuum issue on neuro-ophthalmology. Dr Van Stavern is the Robert C Drews professor of ophthalmology and visual sciences at Washington University in Saint Louis. Dr Van Stavern, welcome, and thank you for joining us today. Why don't you introduce yourself to our audience? Dr Van Stavern: Hi, my name is Gregory Van Stavern. I'm a neuro-ophthalmologist located in Saint Louis, and I'm pleased to be on this show today. Dr Jones: We appreciate you being here, and obviously, any discussion of the visual system is worthwhile. The visual system is important. It's how most of us and most of our patients navigate the world. Roughly 40% of the brain---you can correct me if I'm wrong---is in some way assigned to our visual system. But it's not just about the sensory experience, right? The afferent visual processing. We also have motor systems of control that align our vision and allow us to accurately direct our vision to visual targets of interest. The circuitry is complex, which I think is intimidating to many of us. It's much easier to see a diagram of that than to describe it on a podcast. But I think this is a good opportunity for us to talk about the ocular motor exam and how it helps us localize lesions and, and better understand diagnoses for certain disorders. So, let's get right to it, Dr Van Stavern. If you had from your article, which is outstanding, a single most important message for our listeners about recognizing or treating patients with ocular motor disorders, what would that message be? Dr Van Stavern: Well, I think if we can basically zoom out a little to the big picture, I think it really emphasizes the continuing importance of the examination. History as well, but the examination. I was reading an article the other day that was essentially downplaying the importance of the physical examination in the modern era with modern imaging techniques and technology. But for neurology, and especially neuro-ophthalmology, the history and the examination should still drive clinical decision-making. And doing a careful assessment of the ocular motor system should be able to tell you exactly where the lesion is located, because it's very easy to order a brain MRI, but the MRI is, like Forrest Gump might say, it's like a box of chocolates. You never know what you're going to find. You may find a lot of things, but because you've done the history and the examination, you can see if whatever lesion is uncovered by the MRI is the lesion that explains what's going on with the patient. So even today, even with the most modern imaging techniques we have, it is still really important to know what you're looking for. And that's where the oculomotor examination can be very helpful. Dr Jones: I did not have Forrest Gump on my bingo card today, Dr Van Stavern, but that's a really good analogy, right? If you order the MRI, you don't know what you're going to get. And then- and if you don't have a really well-formed question, then sometimes you get misleading information, right? Dr Van Stavern: Exactly. Dr Jones: We'll get into some technology here in a minute, because I think that's relevant for this discussion. I think most of our listeners are going to agree with us that the exam is important in neuro-ophthalmology, and neurology broadly. So, I think you have some sympathetic listeners there. Again, the point of the exam is to localize and then lead to a diagnosis that we can help patients with. When you think about neurologic disorders where the ocular motor exam helps you get to the right diagnosis, obviously disorders of eye movements, but sometimes it's a clue to a broader neurologic syndrome. And you have some nice discussions in your article about the ocular motor clues to Parkinson disease or to progressive supranuclear palsy. Tell us a little more about that. In your practice, which neurologic disorders do you find the ocular motor exam being most helpful? Dr Van Stavern: Well, just a very brief digression. So, I started off being an ophthalmology resident, and I do two years of ophthalmology and then switch to neurology. And during neurology residency, I was debating which subspecialty to go into, and I realized that neuro-ophthalmology touches every other subspecialty in neurology. And it goes back to the fact that the visual system is so pervasive and widely distributed throughout the brain. So, if you have a neurologic disease, there is a very good chance it is going to affect vision, maybe in a minor way or a major way. That's why careful assessment of the visual system, and particularly the oculomotor system, is really helpful for many neurologic diseases. Neuromuscular disease, obviously, myasthenia gravis and certain myopathies affect the eye movements. Neurodegenerative diseases, in particular Parkinson's disease and parkinsonian conditions, often affect the eye movements. And in particular, when you're trying to differentiate, is this classic Parkinson's disease? Or is this progressive supranuclear palsy? Is it some broad spectrum multisystem atrophy? The differences between the eye movement disorders, even allowing for the fact that there's overlap, can really help point in one direction to the other, and again, prevent unnecessary testing, unnecessary treatment, and so on. Dr Jones: Very good. And I think, to follow on a thread from that concept with patients who have movement disorders, in my practice, seeing older patients who have a little bit of restriction of vertical gaze is not that uncommon. And it's more common in patients who have idiopathic Parkinson disease. And then we use that part of the exam to help us screen patients for other neurodegenerative syndromes like progressive nuclear- supranuclear palsy. So, do you have any tips for our listeners to- how to look at, maybe, vertical gaze and say, this is maybe a normal age-related degree of change. This is something that might suggest idiopathic Parkinson disease. Or maybe something a little more progressive and sinister like progressive super nuclear palsy? Dr Van Stavern: Well, I think part of the issue- and it's harder to do this without the visual aspect. One of my colleagues always likes to say for a neurologist, the eye movement exam begins and ends with the neurology benediction, just doing the sign of the cross and checking the eye movements. And that's a good place to start. But I think it's important to remember that all you're looking at is smooth pursuit and range of eye movements, and there's much more to the oculomotor examination than that. There’s other aspects of eye movement. Looking at saccades can be really helpful; in particular, classically, saccadic movements are selectively abnormal in PSP versus Parkinson's with progressive supranuclear palsy. Saccades, which are essentially rapid movements of the eyes---up and down, in this case---are going to be affected in downward gaze. So, the patient is going to have more difficulty initiating downward saccades, slower saccades, and less range of movement of saccades in downgaze. Whereas in Parkinson's, it's classically upward eye movements and upgaze. So, I think that's something you won't be able to see if you're just doing, looking at, you know, your classic, look at your eye movements, which are just assessing, smooth pursuit. Looking carefully at the eye movements during fixation can be helpful. Another aspect of many parkinsonian conditions is saccadic intrusions, where there's quick movements or saccades of the eye that are interrupting fixation. Much, much more common in PSP than in Parkinson's disease. The saccadic intrusions are what we call square-wave jerks because of what they look like. Eye movement recordings are much larger amplitude in PSP and other multisystem atrophy diseases than with Parkinson's. And none of these are perfect differentiators, but the constellation of those findings, a patient with slow downwards saccades, very large amplitude, and frequent saccadic intrusions might point you more towards this being PSP rather than Parkinson's. Dr Jones: That's a great pearl, thinking about the saccades in addition to the smooth pursuit. So, thank you for that. And you mentioned eye movement measurements. I think it's simultaneously impressive and a little scary that my phone can tell when I'm looking at it within a few degrees of visual attention. So, I imagine there are automated tools to analyze eye movement. Tell us, what's the state of the art there, and what should our listeners be aware of in terms of tools that are available and what they can and can't do? Dr Van Stavern: Well, I could tell you, I mean, I see neuro-ophthalmic patients with eye movement disorders every day and we do not have any automated tools for eye movement. We have a ton of imaging techniques for imaging the optic nerve and the retina in different ways, but we don't routinely employ eye movement recording devices. The only time we usually do that is in somebody where we suspect they have a central or peripheral vestibular disease and we send them for vestibular testing, for eye movement recordings. There is interest in using- I know, again, sort of another digression, but if you're looking at the HINTS technique, which is described in the chapter to differentiate central from peripheral disease, which is a very easy, useful way to differentiate central from peripheral or peripheral vestibular disease. And again, in the acute setting, is this a stroke or not a stroke? Is it the brain or is it the inner ear? Part of the problem is that if you're deploying this widespread, the people who are doing it may not be sufficiently good enough at doing the test to differentiate, is a positive or negative test? And that's where some people have started introducing this into the emergency room, these eye movement recording devices, to give the- using, potentially, AI and algorithms to help the emergency room physicians say, all right, this looks like a stroke, we need to admit the patient, get an MRI and so on, versus, this is vestibular neuritis or an inner ear problem, treat them symptomatically, follow up as an outpatient. That has not yet been widely employed. It's a similar way that a lot of institutions are having fundus photography and OCT devices placed in the emergency room to aid the emergency room physician for patients who present with acute vision issues. So, I think that could be the future. It probably would be something that would be AI-assisted or AI-driven. But I can tell you at least at our institution and most of the ones I know of, it is not routinely employed yet. Dr Jones: So maybe on the horizon, AI kind of facilitated tools for eye movement disorder interpretation, but it's not ready for prime time yet. Is that a fair summary? Dr Van Stavern: In my opinion, yes. Dr Jones: Good to know. This has struck me every time I've read about ocular motor anatomy and ocular motor disorders, whether they're supranuclear or intranuclear disorders. The anatomy is complex, the circuitry is very complicated. Which means I learn it and then I forget it and then I relearn it. But some of the anatomy isn't even fully understood yet. This is a very complex real estate in the brainstem. Why do you think the neurophysiology and neuroanatomy is not fully clarified yet? And is there anything on the horizon that might clarify some of this anatomy? Dr Van Stavern: The very first time I encountered this topic as an ophthalmology resident and later as a neurology resident, I just couldn't understand how anyone could really understand all of the circuitry involved. And there is a lot of circuitry that is involved in us simply having clear, single binocular vision with the afferent and efferent system working in concert. Even in arch. In my chapter, when you look at the anatomy and physiology of the smooth pursuit system or the vertical gaze pathways, there's a lot of, I'll admit it, there's a lot of hand waving and we don't completely understand it. I think a lot of it has to do with, in the old days, a lot of the anatomy was based on lesions, you know, lesion this area either experimentally or clinically. And that's how you would determine, this is what this region of the brain is responsible for. Although we've gotten more sophisticated with better imaging, with functional connectivity MRI and so on, all of those have limitations. And that's why I still don't think we completely understand all the way this information is integrated and synthesized, and, to get even more big level and esoteric, how this makes its way into our conscious mind. And that has to do with self-awareness and consciousness, which is a whole other kettle of fish. It's just really complicated. I think when I'm at least talking to other neurologists and residents, I try to keep it as simple as possible from a clinical standpoint. If you see someone with an eye movement problem, try to see if you can localize it to which level you're dealing with. Is it a muscle problem? Is it neuromuscular junction? Is it nerve? Is it nucleus? Is it supranuclear? If you can put it at even one of those two levels, you have eliminated huge territories of neurologic real estate, and that will definitely help you target and tailor your workup. So, again, you're not costing the patient in the healthcare system hundreds of thousands of dollars. Dr Jones: Great points in there. And I think, you know, if we can't get it down to the rostral interstitial nucleus of the medial longitudinal fasciculus, if we can get it to the brainstem, I think that's obviously- that's helpful in its own right. And I imagine, Dr Van Stavern, managing patients with persistent ocular motor disorders is a challenge. We take foveation for granted, right, when we can create these single cortical images. And I imagine it's important for daily function and difficult for patients who lose that ability to maintain their ocular alignment. What are some of the clinical tools that you use in your practice that our listeners should be aware of to help patients that have a persistent supranuclear disorder of ocular movement? Dr Van Stavern: Well, I think you tailor your treatment to the symptoms, and if it's directly due to underlying condition, obviously you treat the underlying condition. If they have sixth nerve palsy because of a skull base tumor, obviously you treat the skull base tumor. But from a practical standpoint, I think it depends on what the symptom is, what's causing it, and how much it's affecting their quality of life. And everyone is really different. Some patients have higher levels of tolerance for blurred vision and double vision. For things- for patients who have double vision, depending upon the underlying cause we can sometimes use prisms and glasses. Prisms are simply- a lot of people just think prism is this, like, mystical word that means a lot. It’s simply just an optical device that bends light. So, it essentially bends light to allow the eyes- basically, the image to fall on the fovea in both eyes. And whether the prisms help or not is partly dependent upon how large the misalignment is. If somebody has a large degree of misalignment, you're not going to fix that with prism. The amount of prism you'd need to bend the light enough to land on the fovea in both eyes would cause so much blur and distortion that it would essentially be a glorified patch. So, for small ranges of misalignment, prisms are often very helpful, that we can paste over glasses or grind into glasses. For larger degrees of misalignment that- let's say it is due to some skull base tumor or brain stem lesion that is not going to get better, then eye muscle surgery is a very effective option. We usually like to give people a long enough period of time to make sure there's no change before proceeding with eye muscle surgery. Dr Jones: Very helpful. So, prisms will help to a limited extent with misalignment, and then surgery is always an option if it's persistent. That's a good pearl for, I think, our listeners to take away. Dr Van Stavern: And even in those circumstances, even prisms and eye muscle surgery, the goal is primarily to cause single binocular vision and primary gaze at near. Even in those cases, even with the best results, patients are still going to have double vision, eccentric gaze. For most people, that's not a big issue, but we have had a few patients… I had a couple of patients who were truck drivers who were really bothered by the fact that when they look to the left, let's say because it's a 4th nerve palsy on the right, they have double vision. I had a patient who was a golfer who was really, really unhappy with that. Most people are okay with that, but it all depends upon the individual patient and what they use their vision for. Dr Jones: That's a great point. There's not enough neurologists in the world. I know for a fact there are not enough neuro-ophthalmologists in the world, right? There's just not many people that have that dual expertise. You mentioned that you started with ophthalmology and then did neurology training. What do you think the pipeline looks like for neuro-ophthalmology? Do you see growing interest in this among trainees, or unchanged? What are your thoughts about that? Dr Van Stavern: No, that's a continuing discussion we're having within our own field about how to attract more residents into neuro-ophthalmology. And there's been a huge shift. In the past, this was primarily ophthalmology-driven. Most neuro-ophthalmologists were trained in ophthalmology initially before doing a fellowship. The last twenty years, it switched. Now there's an almost 50/50 division between neurologists and ophthalmologists, as more neurologists have become more interested. This is probably a topic more for the ophthalmology equivalent of Continuum. One of the perceptions is this is not a surgical subspecialty, so a lot of ophthalmology residents are disincentivized to pursue it. So, we have tried to change that. You can do neuro-ophthalmology and do eye muscle surgery or general ophthalmology. I think it really depends upon whether you have exposure to a neuro-ophthalmologist during your neurology residency. If you do not have any exposure to neuro-ophthalmology, this field will always seem mysterious, a huge black box, something intimidating, and something that is not appealing to a... /episode/index/show/continuumjournal/id/35872525

Approach to Diplopia With Dr. Devin Mackay 05/07/2025

Approach to Diplopia With Dr. Devin Mackay Double vision is a symptom often experienced by patients with neurologic disease. An organized systematic approach to evaluating patients with diplopia needs a foundational understanding of the neuroanatomy and examination of eye movements and ocular alignment. In this episode, Teshamae Monteith, MD, FAAN, speaks with Devin Mackay, MD, FAAN, author of the article “Approach to Diplopia” in the Continuum® April 2025 Neuro-ophthalmology issue. Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida. Dr. Mackay is an associate professor of neurology, ophthalmology, and clinical neurosurgery at Indiana University School of Medicine in Indianapolis, Indiana. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Monteith: This is Dr Teshamae Monteith. Today I'm interviewing Dr Devin Mackay about his article on approach to diplopia, which appears in the April 2025 Continuum issue on neuro-ophthalmology. Welcome to the podcast. How are you? Dr Mackay: Thank you. It's great to be here. Dr Monteith: Congratulations on your article. Dr Mackay: Thank you. I appreciate that. Dr Monteith: Why don't you start off with introducing yourself to our audience? Dr Mackay: So, yeah, my name is Devin Mackay. I'm a neuro-ophthalmologist at Indiana University. I did my residency at what was used to be known as the Partners Healthcare Program in Boston, and I did a fellowship in neuro-ophthalmology in Atlanta. And I've been in practice now for about ten years. Dr Monteith: Oh, wow. Okay. Tell us a little bit about your goals when you were writing the chapter. Dr Mackay: So, my goal with the approach to double vision was really to demystify double vision. I think double vision is something that as trainees, and even as faculty members and practicing neurologists, we really get intimidated by, I think. And it really helps to have a way to approach it that demystifies it and allows us to localize, just like we do with so many other problems in neurology. Dr Monteith: I love that, demystification. So why don't you tell us what got you interested in neuro-ophthalmology? Dr Mackay: Yeah, so neuro-ophthalmology I stumbled on during a rotation during residency. We rotated in different subspecialties of neurology and I did neuro-ophthalmology, and I was just amazed by the exam and how intricate it was, the value of neuroanatomy and localization, the ability to take a complicated problem and kind of approach it as a diagnostic specialist and really unravel the layers of it to make it better. To, you know, figure out what the problem is and make it better. Dr Monteith: Okay, so you had a calling, clearly. Dr Mackay: I sure did. Dr Monteith: You talked about latest developments in neuro-ophthalmology as it relates to diplopia. Why don't you share that with our listeners? Dr Mackay: Yeah. So, you know, double vision is something that's really been around since the beginning of time, essentially. So that part hasn't really changed a lot, but there are some changes that have happened in how we approach double vision. Probably one of the bigger ones has been, we used to teach that with a, you know, patient over the age of fifty with vascular risk factors who had a cranial nerve palsy of cranial nerves 3, 4, or 6, we used to automatically assume that was a microvascular palsy and we just wouldn't do any more testing and we'd just, you know, wait to see how they did. And it turns out we're missing some patients who have significant pathologies, sometimes, with that approach. And so, we've really shifted our teaching with that to emphasize that it's a lot easier to get an MRI, for example, than it ever has been. And it can be important to make sure we're not missing important pathology in patients, even if they have vascular risk factors over the age of fifty and they just have a cranial nerve 3, 4, or 6 palsy. So that's been one change. Dr Monteith: Interesting. And why don't you tell us a little bit about the essential points that you want to get across in the article? Dr Mackay: Yeah. So, I think one is to have a systematic approach to double vision. And a lot of that really revolves around localization. And it even begins with the history that we take from the patients. There's lots of interesting things we can ask about double vision from the patient. For example, the most important thing you can ever ask someone with double vision is, does it go away when you cover either eye? And that really helps us figure out the first question for us as neurologists, which is, is it neurologic or non-neurologic? If it's still there when covering one eye, then it is not neurologic and that's usually a problem for an ophthalmologist to sort out. So that's really number one. And then if it is binocular double vision, then we get into details about, is it horizontal or vertical misalignment? Is it- what makes it better and worse? Is there an associated ptosis or other symptoms? And based on all of that, we can really localize the abnormality with the double vision and get into details about further testing if needed, and so forth. I also love that that approach really reduces our need to rely on things like neuroimaging sometimes when we may not need it, or on other tests. So, I think it really helps us be more efficient and really take better care of patients. Dr Monteith: So definitely that cover/uncover test, top thing there. Your approach- and you mentioned, are you really getting that history, and are there any other kind of key factors when you're approaching diplopia before getting into some of the details? Dr Mackay: Yeah, that's a good question. I think also having some basics of how to examine the patient, because double vision is such a challenging thing. A lot of us aren't as familiar with the exam toolkit, so to speak, of what you would do with a patient with double vision. And so, I go over in the article a bit about a Maddox rod, which is a handy little tool that I always keep in my pocket of my lab coat. It allows you to assign a red line to one eye and a light to the other eye, and you can see if the eyes line up or not. And you don't need any other special equipment, you just need the light in that Maddox rod. That really helps us understand a lot about the pattern of misalignment, which is really important for evaluating double vision. So, for example, if someone has a right 6th nerve palsy, I'll expect a horizontal misalignment of the eyes that worsens when the patient looks to the right and improves when they look to the left. And especially if it's a partial palsy, it's not always easy to see that just by looking at their eye movements. And having a way to really measure the eye alignment and figure out, is it worse or better in certain directions, is really essential to localization, I think, in a lot of cases. Dr Monteith: You caught me. I skipped over that Maddox rod part, even though you spent a lot of time talking about Maddox rods. Kind of skipped over it. So, you're saying that I need one. Dr Mackay: Everyone needs one. I've converted some of our residents here to carry one with them. And yeah, I realize it's a daunting tool at first, but when you have a patient with double vision and their eye movements look normal, I feel like a lot of neurologists are- kind of, their hands seem like they're tied and they’re like, oh, I don't know, I don't know what to do at this point. And if you can get some more details with a simple object like that, it can really change things. Dr Monteith: So, we’ve got to talk to the AAN store and make sure that they have enough of these, because now there's going to be lots of… Dr Mackay: We're going to sell out on Amazon today now because of this podcast. Dr Monteith: Cyber Monday. So, let's talk about the H pattern. And I didn't know it had the- well, yeah, I guess the official name is “H pattern.” In medical school, I mean, that's what I learned. But as a resident and, you know, certainly as an attendee, I see people doing all sorts of things. You're pro-H pattern, but are there other patterns that you also respect? Dr Mackay: It depends on what you're looking for, I think. The reason I like the H pattern is because you get to look at upgaze and downgaze in two different directions. So, you get to look at upgaze and downgaze when looking to the left, and up- and downgaze when looking to the right. And the reason that matters is because vertical movements of the eyes are actually controlled by different eye muscles depending on whether the eye is adducted toward the nose or abducted away from the nose. And so that's why I love the H pattern, is because it allows you to see that. If you just have them look up and down with just a cross pattern, for example, then you really lose that specificity of looking at both the adduction and abduction aspects. So, it's not wrong to do it another way with, like, the cross, for example, but I just think there are some cases where we'll be missing some information, and sometimes that can actually make a difference. Dr Monteith: Well, there you have it. Let's talk a little bit about eliciting diplopia during the neurologic exam. What other things should we be looking out for? Dr Mackay: So, in terms of eliciting diplopia, it really starts with the exam and again, figuring out, are we covering one eye? And figuring out, is this patient still having double vision? It's tricky because sometimes the patients won't even know the answer to that question or they've never done it, they’ve never covered one eye. And so, if that's the case, I really make them do it in the office with me and it's like, okay, well, are we having double vision right now? Well, great, okay, we are, then we're going to figure this out right now. And we cover one eye and say, is it still double? And that way we can really figure out, are we monocular or binocular? That's always step one. And then if we've established that it's binocular diplopia, then that's when we get into the other details that I mentioned before. And then as far as other things to look for, we're always in tune to other things that are going on in terms of symptoms, like ptosis, or if there's bulbar weakness, or some sensory change or motor problem that seems to be associated with it. Obviously, those will give us clues in the localization as well. Dr Monteith: And what about ocular malalignment? Dr Mackay: Yeah. So ocular malalignment, really, the cardinal symptom of that is going to be double vision. And so, if a patient has a misalignment of the eyes and they don't have double vision, then usually that means either we're wrong and they don't have double vision, or they do have double vision and they, you know, haven't said it correctly. Or it could be that the vision is poor in one eye. Sometimes that can happen. Or, some patients were actually born with an eye misalignment and their brain has learned in a way to kind of tune out or not allow the proper development of vision in one eye. And so that's also known as amblyopia, also known as the lazy eye, some people call it. But that finding can also make someone not experience double vision. But otherwise, if someone's had normal vision kind of throughout their life, they'll usually be pretty aware of when they first notice double vision. It'll be an obvious event for them in in most cases. Dr Monteith: And then the Cogan lid twitch? Dr Mackay: Oh yes, the Cogan lid twitch. So, the Cogan lid twitch is a feature of myasthenia gravis. The way you elicit it is, you have the patient look down. I'm not sure there's a standardization for how long; you want to have it long enough that you're resting the levator muscle, which is the muscle that pulls the upper lid open. And so, you rest that by having them look down for… I usually do about ten or fifteen seconds. And then I have them look up to looking straight forward. And you want to pay careful attention to their lid position as their eye settles in that straight-forward position. What will happen with a Cogan's lid twitch is, the lid will overshoot, and then it'll come back down and settle into its, kind of, proper position. And what we think is happening there is, it's almost like a little mini “rest test” in a way, where you're resting that muscle just long enough to allow some of the neurotransmission to recover. You get a normal contraction of the muscle, but it fades very quickly and comes back down. And that's experienced as a twitch. Dr Monteith: So, the patient can feel it. And it's something you can see? Dr Mackay: Yeah, the patient may not feel it as much. It's usually it's going to be something that the clinician can see if they're looking for it. And I would say that's one of the physical exam findings that can be a hallmark of myasthenia gravis, but certainly not the only one. Some others that we often look for are fatigable ptosis with sustained upgaze. You have the patient look up for a prolonged time and you'll see the lid droop down. So that can be one. Ice pack test is very popular nowadays, and it has pretty good sensitivity and specificity for myasthenia. So, you keep an ice pack over the closed eyes for two minutes and you compare the lid position before and after the ice pack test. And in the vast majority of myasthenia patients, if they have ptosis, the ptosis will have resolved, or at least significantly improved, in those patients. And yet one more sign is, if you find the patient's eye with ptosis and you lift open the eye manually, you'll often see that the other eyelid and the other eye will lower down. So, I'm not sure there's a name for that, but that can be a helpful sign as well. Dr Monteith: Since you're going through some of these, kind of, key features of different neurologic disease, why don't you tell us about a few others? Dr Mackay: Yeah, so another I mentioned in the in the article is measurement of levator function, which is really a test of eyelid strength. And so, that can be helpful if we have- someone has ptosis, or we're not sure if they have ptosis and we're trying to evaluate that to see if it's linked to the double vision, because that really changes the differential if ptosis is part of the clinical situation. So, the way that's measured is you have a patient look down as far as they can. And you get out a little ruler---I usually use a millimeter ruler---and I set the zero of the ruler at the upper lid margin when they're looking down. So, I hold the ruler there, and then I ask the patient to look up as far as they can without moving their head. Where the lid position stops of the upper lid is the new point on the ruler. And so, you measure that and see how much that is. And so, a normal patient may have a value somewhere between, I don't know, twelve or thirteen millimeters up to seventeen or eighteen millimeters, probably, in most cases. Especially if there is an asymmetric lid position, if you find that the levator function is symmetric, then it tells you that the muscle is working fine and that the ptosis is not from the muscle. So then the ptosis may be from dehiscence of the lid margin from the muscle. And so, that's a really common cause of ptosis, and that's often age-related or trauma-related. And we can dismiss that as being part of the symptom constellation of double vision. So, it can be really helpful to clarify, is this a muscle problem, which you'd expect with myasthenia or a third nerve palsy, or is this a mechanical problem with the lid, which is non-neurologic and really should be dismissed? So that can be a really helpful exam tool. Dr Monteith: So, you're just now getting into a little localization. So why don't we kind of start from the most proximal pistol with localization. Give us a little bit of tips. I know they just got to read your article, but give us a few tips. Dr Mackay: So, in terms of most proximal causes, there are supranuclear causes of ocular misalignment. For example, a skew deviation would qualify as that. Anything that's happening from some deficient input before you get to the cranial nerve nuclei, that we would consider supranuclear. So, we also see that with things like progressive supranuclear policy and certain other conditions. And then there can be lesions of the cranial nerve nuclei themselves. So, cranial nerves 3, 4, and 6 all have nuclei, and if they're lesioned they will cause double vision in specific patterns. And then there's also another subgroup, which is known as intranuclear problems with eye alignment. And so, the most common of that is going to be intranuclear ophthalmoplegia. And so that's very common in patients with demyelinating disorders, or it can also happen with strokes and tumors and other causes. And then there's infranuclear problems, which are from the cranial nerve nuclei out, and so those would be the cranial nerves themselves. So that's where your microvascular palsies, any tumor pressing on the nerve in those locations can cause palsies like that, any inflammatory disorder along that course. Then as we get more distal, we get into the orbit, we have the neuromuscular junction---so, the connection between the nerve and the muscle. And of course, that's our myasthenia gravis. And there are rare causes, things like botulinum and tick borne illnesses and certain other things that are more rare. And then, of course, we get to the muscle itself, and there can be different muscular dystrophies, different things like myositis or inflammatory disorders of the orbit or even physical trauma. So, if a patient, you know, had a trauma in trapping an extraocular muscle, that can be a localization. So really, anywhere along that pathway you can have double vision. So, I love to approach it from that perspective to help narrow down the diagnostic possibilities. Dr Monteith: Okay, just like everything? Dr Mackay: Just like all of the rest of the neurology. See, it's not that scary. Dr Monteith: You know, and so, yeah. And then you do a lot more than, you know, a few cranial nerves, right? Dr Mackay: Right. That's right. There's a lot more to double vision than that. I think as neurologists, we get lost if it's not a cranial nerve palsy, we're like, oh, I don't know what this is. And if it's not myasthenia, not a cranial nerve palsy. But it's worth also considering that there are ophthalmologic causes of someone having double vision that we often don't consider. So maybe someone who was born with strabismus, or maybe they have a little bit of a tendency toward an eye misalignment that their brain compensates, for and then it decompensates someday and that now they have a little bit of double vision intermittently, so that those can be causes to consider as well. Dr Monteith: Yeah, well, we'll just have to, you know, request those records from forty years ago. No problem. Dr Mackay: That's right. Dr Monteith: Why don't you also give us a little bit of tip when we're on the wards and we want to teach either a medical student or a resident, or if it's a resident listening, may want to teach a junior resident and seem like a star when approaching a patient with diplopia. Give us some teaching pearls. Dr Mackay: Yeah. So, I would love people teaching more about this at the bedside. I'd say probably the first thing to do would be to equip yourself by recognizing... /episode/index/show/continuumjournal/id/35872505

Papilledema With Dr. Susan Mollan 04/30/2025

Papilledema With Dr. Susan Mollan Papilledema describes optic disc swelling (usually bilateral) arising from raised intracranial pressure. Due to its serious nature, there is a fear of underdiagnosis; hence, one major stumbling points is correct identification, which typically requires a thorough ocular examination including visual field testing. In this episode, Kait Nevel, MD speaks with Susan P. Mollan, MBChB, PhD, FRCOphth, author of the article “Papilledema” in the Continuum® April 2025 Neuro-ophthalmology issue. Dr. Nevel is a Continuum® Audio interviewer and a neurologist and neuro-oncologist at Indiana University School of Medicine in Indianapolis, Indiana. Dr. Mollan is a professor and neuro-ophthalmology consultant at University Hospitals Birmingham in Birmingham, United Kingdom. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Nevel: Hello, this is Dr Kait Nevel. Today I'm interviewing Dr Susan Mollan about her article Papilledema Diagnosis and Management, which appears in the April 2025 Continuum issue on neuro-ophthalmology. Susie, welcome to the podcast, and please introduce yourself to our audience. Dr Mollan: Thank you so much, Kait. It's a pleasure to be here today. I'm Susie Mollan, I'm a consultant neuro-ophthalmologist, and I work at University Hospitals Birmingham- and that's in England. Dr Nevel: Wonderful. So glad to be talking to you today about your article. To start us off, can you please share with us what you think is the most important takeaway from your article for the practicing neurologist? Dr Mollan: I think really the most important thing is about examining the fundus and actually trying to visualize the optic nerves. Because as neurologists, you're really acutely trained in examining the cranial nerves, and often people shy away from looking at the eyes. And it can give people such confidence when they're able to really work out straightaway whether there's going to be a problem or there's not going to be a problem with papilledema. And I guess maybe a little bit later on we can talk about the article and tips and tricks for looking at the fundus. But I think that would be my most important thing to take away. Dr Nevel: I'm so glad that you started with that because, you know, that's something that I find with trainees in general, that they often find one of the more daunting or challenging aspects of learning, really, how to do an excellent neurological exam is examining the fundus and feeling confident in diagnosing papilledema. What kind of advice do you give to trainees learning this skill? Dr Mollan: So, it really is practice and always carrying your ophthalmoscope with you. There's lots of different devices that people can choose to buy. But really, if you have a direct ophthalmoscope, get it out in the ward, get it out in clinic. Look at those patients that you'd know have alternative diagnosis, but it gives you that practice. I also invite everybody to come to the eye clinic because we have dilated patients there all the time. We have diabetic retinopathy clinics, and it makes it really easy to start to acquire those skills because I think it's very tricky, because you're getting a highly magnified view of the optic nerve and you've got to sort out in your head what you're actually looking at. I think it's practice. and then use every opportunity to really look at the fundus, and then ask your ophthalmology colleagues whether you can go to clinic. Dr Nevel: Wonderful advice. What do you think is most challenging about the evaluation of papilledema and why? Dr Mollan: I think there are many different aspects that are challenging, and these patients come from lots of different areas. They can come from the family doctor, they can come from an optician or another specialist. A lot of them can have headache. And, as you know, headache is almost ubiquitous in the population. So, trying to pull out the sort of salient symptoms that can go across so many different conditions. There's nothing that's pathognomonic for papilledema other than looking at the optic nerves. So, I think it's difficult because the presentation can be difficult. The actual history can be challenging. There are those rare patients that don't have headache, don't have pulsatile tinnitus, but can still have papilledema. So, I think it- the most challenging thing is actually confirming papilledema. And if you're not able to confirm it, getting that person to somebody who's able to help and confirm or refute papilledema is the most important thing. Dr Nevel: Yeah, right. Because you talk in your article the importance of distinguishing between papilledema and some other diagnoses that can look like papilledema but aren't papilledema. Can you talk about that a little bit? Dr Mollan: Absolutely. I think in the article it's quite nice because we were able to spend a bit of time on a big table going through all the pseudopapilledema diagnoses. So that includes people with shortsightedness, longsightedness, people with optic nerve head drusen. And we've been very fortunate in ophthalmology that we now have 3D imaging of the optic nerve. So, it makes it quite clear to us, when it's pseudopapilledema, it's almost unfair when you're using the direct ophthalmoscope that you don't get a cross sectional image through that optic nerve. So, I'd really sort of recommend people to delve into the article and look at that table because it nicely picks out how you could pick up pseudopapilledema versus papilledema. Dr Nevel: Perfect. In your article, you also talk about what's important to think about in terms of causes of papilledema and what to evaluate for. Can you tell us, you know, when you see someone who you diagnose with papilledema, what do you kind of run through in terms of diagnostic tests and things that you want to make sure you're evaluating for or not missing? Dr Mollan: Yeah. So, I think the first thing is, is once it's confirmed, is making sure it's isolated or whether there's any additional cranial nerve palsies. So that might be particularly important in terms of double vision and a sixth nerve palsy, but also not forgetting things like corneal sensation in the rest of the cranial nerves. I then make sure that we have a blood pressure. And that sounds a bit ridiculous in this day and age because everybody should have a blood pressure coming to clinic or into the emergency room. But sometimes it's overlooked in the panic of thinking, gosh, I need to investigate this person. And if you find that somebody does have malignant hypertension, often what we do is we kind of stop the investigational pathway and go down the route of getting the medics involved to help with lowering the blood pressure to a safe level. I would then always think about my next thing in terms of taking some bloods. I like to rule out anemia because anemia can coexist in a lot of different conditions of raised endocranial pressure. And so, taking some simple blood such as a complete blood count, checking the kidney function, I think is important in that investigational pathway. But you're not really going to stop there. You're going to move on to neuroimaging. It doesn't really matter what you do, whether you do a CT or an MRI, it's just getting that imaging pretty much on the same day as you see the patient. And the key point to that imaging is to do venography. And you want to rule out a venous sinus thrombosis cause that's the one thing that is really going to cause the patient a lot of morbidity. Once your neuroimaging is secure and you're happy, there's no structural lesion or a thrombosis, it's then reviewing that imaging to make sure it's safe to proceed with lumbar puncture. And so, we would recommend the lumbar puncture in the left lateral decubitus position and allowing the patient to be as calm and relaxed as possible to be able to get that accurate opening pressure. Once we get that, we can send the CSF for contents, looking for- making sure they don't have any signs of meningitis or raised protein. And then, really, we're at that point of saying, you know, we should have a secure diagnosis, whether it would be a structural lesion, venous sinus thrombosis, or idiopathic intracranial hypertension. Dr Nevel: Wonderful. Thank you for that really nice overview and, kind of, diagnostic pathway and stepwise thought process in the evaluations that we do. There are several different treatments for papilledema that you go through in your article, ranging from surgical to medication options. When we're taking care of an individual patient, what factors do you use to help guide you in this decision-making process of what treatment is best for the patient and how urgent treatment is? Dr Mollan: I think that's a really important question because there's two things to consider here. One is, what is the underlying diagnosis? Which, hopefully, through the investigational save, you'll have been able to achieve a secure diagnosis. But going along that investigational pathway, which determines the urgency of treatment, is, what's happening with the vision? If we have somebody where we're noting that the vision is affected- and normally it's actually through a formal visual field. And that's really challenging for lots of people to get in the emergency situation because syndromes of raised endocranial pressure often don't cause problems with the visual acuity or the color vision until it's very late. And also, you won't necessarily get a relative afferent papillary defect because often it's bilateral. So I really worry if any of those signs are there in somebody that may have papilledema. And so, a lot rests on that visual field. Now, we're quite good at doing confrontational visual fields, but I would say that most neurologists should be carrying pins to be able to look at the visual fields rather than just pointing fingers and quadrants if you're not able to get a formal visual field early. It's from that I would then determine if the vision is affected, I need to step up what I'm going to do. So, I think the sort of next thing to think about is that sort of vision. So, if we have somebody who, you know, you define as have severe sight loss at the point that you're going through this investigational pathway, you need to get an ophthalmologist or a neuro-ophthalmologist on board to help discuss either the surgery teams as to whether you need to be heading towards an intervention. And there are a number of different types of intervention. And the reason why we discuss it in the article---and we'll also be discussing it in a future issue of Continuum---is there's not high-class evidence to suggest one surgery over another surgery. We may touch on this later. So, we've got our patients with severe visual loss who we need to do something immediately. We may have people where the papilledema is moderate, but the vision isn't particularly affected. They may just have an enlarged blind spot. For those patients, I think we definitely need to be thinking about medical therapy and talking to them about what the underlying cause is. And the commonest medicine to use for raised endocranial pressure in this setting is acetazolamide, a carbonic anhydrous inhibitor. And I think that should be started at the point that you believe somebody has moderate papilledema, with a lot of discussion around the side effects of the medicine that we go into the article and also the fact that a lot of our patients find acetazolamide in an escalating dose challenging. There are some patients with very mild papilledema and no visual change where I might say, hey, I don't think we need to start treatment immediately, but you need to see somebody who understands your disease to talk to you about what's going on. And generally, I would try and get somebody out of the emergency investigational pathway and into a formal clinic as soon as possible. Dr Nevel: Thank you so much for that. One thing that I was wondering that we see clinically is you get a consult for a patient, maybe, who had an isolated episode of vertigo, back to their normal self, completely resolved… but incidentally, somebody ordered an MRI. And that MRI, in the report, it says partially empty sella, slight flattening of the posterior globe, concerns for increased intracranial pressure. What should we be doing with these patients who, you know, normal neurological exam, maybe we can't detect any definite papilledema on our endoscopic exam. What do you think the appropriate pathway is for those patients? Dr Mollan: I think it's really important. The more neuroimaging that we're doing, we're sort of seeing more people with signs that are we don't believe are normal. So, you've mentioned a few, the sort of partially empty sella, empty sella, tortuosity of the optic nerves, flattening of the globes, changes in transverse sinus. And we have quite a nice, again, table in the article that talks about these signs. But they have really low sensitivity for a diagnosis of raised endocranial pressure and isolation. And so, I think it's about understanding the context of which the neuroimaging has been taken, taking a history and going back and visiting that to make sure that they don't have escalating headache. And also, as you said, rechecking the eye nerves to make sure there's no papilledema. I think if you have a good examination with the direct ophthalmoscope and you determine that there's no papilledema, I would be confident to say there's no papilledema. So, I don't think they need to necessarily cry doubt. The ophthalmology offices, we certainly are having quite a few additional referrals, particularly for this, which we kind of called IIH-RAD, where patients are coming to us for this exclusion. And I think, in the intervening time, patients can get very anxious about having a sort of MRI artifact picked up that may necessarily mean a different diagnosis. So, I guess it's a little bit about reassurance, making sure we've taken the appropriate history and performed the examination. And then knowing that actually it's really a number of different signs that you need to be able to confidently diagnose raised ICP, and also the understanding that sometimes when people have these signs, if the ICP reduces, those signs remain. You know, we're learning an awful lot more about MRI imaging and what's normal, what's within normal limits. So, I think reassurance and sensible medical approach. Dr Nevel: Absolutely. In the section in your article on idiopathic intracranial hypertension, you spend a little bit of time talking about how important it is that we sensitively approach the topic of potential weight loss for those patients who are overweight. How do you approach that discussion in your clinic? Because I think it's an important part of the holistic patient care with that condition. Dr Mollan: I think this is one of the things that we've really listened to the patients about over the last number of years where we recognize that in an emergency situation, sometimes we can be quite quick to sort of say, hey, you have idiopathic endocranial hypertension and weight loss is, you know, the best treatment for the condition. And I think in those circumstances, it can be quite distressing to the patient because they feel that there's a lot of stigma attached around weight management. So, we worked with the patient group here at IIH UK to really come up with a way of a signposting to our patients that we have to be honest that there is a link, you know, a strong evidence that weight gain and body shape change can cause someone to fall into a diagnosis of IIH. And we know that weight loss is really effective with this condition. So, I think where I've learned from the patients is trying to use language that's less stigmatizing. I definitely signpost that I'm going to talk about something sensitive. So, I say I'm going to talk about something sensitive and I'm going to say, do you know that this condition is related to body shape change? And I know that if I listen to this podcast in a couple of years, I'm sure my words will have changed. And I think that's part of the process, is learning how to speak to people in an ever-changing language. And they think that sort of signpost that you're going to talk about something sensitive and you're going to talk about body shape change. And then follow up with, are you OK with me talking about this now? Is it something you want to talk about? And the vast majority of people say, yes, let's talk about it. There'll be a few people that don't want to talk about it. And I usually come in quite quickly, say, is it OK if I mention it at the next consultation? Because we have a duty of care to sort of inform our patients, but at the same time we need to take them on that journey to get them back to health, and they need to be really enlisted in that process. Dr Nevel: Yeah, I really appreciate that. These can be really difficult conversations and uncomfortable conversations to have that are really important. And you're right, we have a duty as medical providers to have these conversations or inform our patients, but the way that we approach it can really impact the way patients perceive not only their diagnosis, but the relationship that we have with our patients. And we always want that to be a positive relationship moving forward so that we can best serve our patients. Dr Mollan: I think the other thing as well is making sure that you've got good signposts to the professionals. And that's what I say, because people then say to me, well, you know, kind of what diet should I be on? What should I be doing? And I say, well, actually, I don't have professional experience with that. I'm, I'm very fortunate in my hospital, I'm able to send patients to the endocrine weight management service. I'm also able to send patients to the dietetic service. So, it's finding, really, what suits the patient. Also what's within licensing in your healthcare system to be able to provide. But not being too prescriptive, because when you spend time with weight management professionals, they'll tell you lots of different things about diets that people have championed and actually, in randomized controlled trials, they haven't been effective. I think it's that signpost really. Dr Nevel: Yeah, absolutely. So, could you talk a little bit about what's going on in research in papilledema or in this area, and what do you think is up-and-coming? Dr Mollan: I think there's so much going on. Mainly there's two parts of it. One is image analysis, and we've had some really fantastic work out of the Singapore group Bonsai looking at a machine learning decision support tool. When people take fundal pictures from a normal fundus camera, they're able to say with good certainty, is this papilledema, is this not papilledema? But more importantly, if you talk to the investigators, something that we can't tell when we look in is they're able to, with quite a high level of certainty, say, well, this is base occupying lesion, this is a venous sinus thrombosis, and this is IIH. And you know, I've looked at thousands and thousands of people's eyes and that I can't tell why that is. So, I think the area of research that is most exciting, that will help us all, is this idea about decision support tools. Where, in your emergency pathway, you're putting a fundal camera in that helps you be able to run the image, the retina, and... /episode/index/show/continuumjournal/id/35872470

Optic Neuritis With Dr. Eric Eggenberger 04/23/2025

Optic Neuritis With Dr. Eric Eggenberger The inflammatory and infectious optic neuropathies are a broad, heterogeneous, and common group of diseases producing visual loss. Although many now-distinct syndromes have been previously combined as “typical or atypical optic neuritis,” recent developments highlight the importance of precision terminology as well as an individualized evaluation and treatment approach. In this episode, Gordon Smith, MD, FAAN speaks with Eric Eggenberger, DO, MS, FAAN, author of the article “Optic Neuritis” in the Continuum® April 2025 Neuro-ophthalmology issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Eggenberger is a professor of ophthalmology, neurology, and neurosurgery at the Mayo Clinic in Jacksonville, Florida. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Smith: This is Dr Gordon Smith. Today I'm interviewing someone who really needs no introduction, Dr Eric Eggenberger, about his article on optic neuritis, which appears in the April 2025 Continuum issue on neuro-ophthalmology. Eric, welcome to the podcast, and maybe you can introduce yourself to our audience. Dr Eggenberger: Thank you. Thanks for having me. So, my name is Eric Eggenberger. I work at Mayo Clinic Florida, and I am involved exclusively in neuro-ophthalmology. Dr Smith: I just had the pleasure, Eric, of talking yesterday with Lindsey De Lott about non-optic neuritis causes of optic neuropathy. And so, I'm going to kind of reference a little bit what I learned yesterday. She was great. I wonder if you might begin by talking a little bit about nomenclature. You talk about the need for use of precise terminology in your article. And yesterday she taught me a lot about the risk of misdiagnosis and other causes of optic neuropathy, and the two seem related. So, I wonder if you can maybe lay the foundation for our conversation by talking about terminology? Dr Eggenberger: I think that's a great point. So, we are in an era now where, instead of lumping all these different diagnoses together, we have learned to split apart some of these clinical entities. And so, I think it's really important that we focus on precise terminology and recognize that all optic neuritis is not the same. And we have very different, distinct clinical pathways for these imaging pathways, treatment pathways, for these different types of optic neuritis, whether that's MS related, whether it's MOG related or aquaporin-4 related. Dr Smith: So, I wonder maybe we can begin by just, you know, giving our listeners wisdom, pearls, and pitfalls about, how do you recognize when someone with a suspected optic neuropathy has optic neuritis versus a noninflammatory optic neuropathy? Dr Eggenberger: So, that's a really important issue because there's a lot of clinical overlap in terms of exam findings. So, for instance, in any optic neuropathy, let's say it's unilateral, you typically are going to see decreases in acuity and field and color, and you're going to see a relative afferent pupillary defect. And then it's really the context that that occurs in that helps us distinguish different disease entities. So, with optic neuritis, typically you're going to have pain. And that's oftentimes going to be in the younger populations compared to some of the other common optic neuropathies we see, like ischemic optic neuropathy, for instance. Dr Smith: Right. So maybe we can talk a little bit about, kind of, your overall diagnostic approach, right? A lot of this is, of course, based on age and context, but young people get ischemic lesions and older people can have inflammatory lesions. So, what's your overall approach to the patient you just described? Let's say it's a forty-eight-year-old woman who comes to the emergency department with subacute unilateral vision loss and there's dyschromatopsia, APD, reduced acuity. And, you know, let's just say a fairly, you know, benign-looking fundoscopic exam. What do you do to evaluate that patient? Dr Eggenberger: In that particular context, I think we're looking at other contextual clues. Is there other vascular risk factors or other things to point you in one direction or the other? One of the important parts you mentioned was the fundus exam. So, we know with ischemic optic neuropathy, 100% of the time with AIOM, you're going to see disc edema. And so, in the context of that story, we want to confirm on our exam an optic neuropathy, and then we can kind of focus on the retrobulbar courses or different types of optic neuropathies. From an exam perspective, in that particular patient we’d be looking to measure the acuity, quantify that. And in the ER, you're not going to be able to do a perfect field, but you'll get some sense of the field and how much field loss there is. And then as you mentioned, the afferent pupillary defect is critical. And we're going to get a little bit of the historical features in terms of pain. With typical retrobulbar optic neuritis, most of those patients are going to experience some pain, and usually it's pain on eye movements. And those would be the clinical things to focus on. Other exposures the patient may or may not have had, any other concomitant conditions, would all help point you in different directions, perhaps, and then we're probably on towards imaging. Dr Smith: Yeah, maybe you can talk a little bit about that? What's the appropriate use of imaging? I mean, presumably the patients, like the one I just threw out there, are pretty much all going to get neuroimaging. What's your approach to that? How do you protocol the study? What should we be looking for? Dr Eggenberger: In our clinic, we would typically be ordering an MRI orbit and brain, and each of those has a specific purpose. The orbit is going to show us the extent of the optic neuropathy. So, we're particularly looking for a longitudinally extensive optic nerve lesion or more than half of the optic nerve involved. And most patients acutely, if it isn't an “itis" situation, we'll see enhancement. And then the MR brain is going to be useful for looking for other evidence of demyelination within the central nervous system. We may at some point get down to doing an MR cord, but I think acutely it's going to be brain and orbit that most of our patients are getting. Dr Smith: Let's say that we did the scan and, sure enough, there's sort of a shorter segment, so less than half the length of the nerve region of enhancement. What's the rest of your diagnostic evaluation look like for that patient? Dr Eggenberger: So, in that particular case, we would look at the remainder of the brain. So, we're looking for other evidence of demyelination and any other contextual clues, systemically that would point you one direction or another. But with a shorter segment involved, one of the more common things we might encounter would be multiple sclerosis-related optic neuritis. Dr Smith: Would you look for aquaporin-4 and MOG in a patient with what appears to be an isolated, uncomplicated short segment optic neuritis? Dr Eggenberger: So, I think it really depends a bit on the context. I would never fault anybody for looking at MOG or an aquaporin-4 in that context because those are really treatment-altering diagnoses, but the yield in this particular case with a short segment involved and depending on the acuity and other features is probably going to be pretty low. Dr Smith: I really liked as an aside- I wasn't going to go there next, but you kind of got me thinking about it, you have a really nice section in your article. Which, all of it's great, but talking about how to manage low titer MOG antibodies. I wonder if you could talk about that because I think that's a lesson, maybe, that is transferable to a lot of other testing that we do. in terms of pre-prior probability and titer and so forth. Dr Eggenberger: Yeah, that's really an important point. So, we've seen this come up a number of times where the MOG antibody is a very good test, but in low titer it has a relatively low positive predictive value, perhaps 50%. In those cases, particularly without a classic clinical context, you have to be extremely alert for some other diagnosis that could mimic what you think is inflammatory demyelinating optic neuritis, but in fact is infectious or some other cause. Dr Smith: Yeah, super, super important and helpful. In terms of aquaporin-4, how does that compare in terms of predictive values, lower titer positive results? Dr Eggenberger: So aquaporin-4, the test has a very high specificity. So, it's quite useful if positive. You have to keep in mind there can be some false negatives, but the test otherwise is quite specific. And that is a diagnosis, you know, we never want to miss. It's a vicious disease. It tends to be a blinding disease, particularly without treatment. Bad things happen when we miss that, and we want to get on that diagnosis early and do pretty aggressive early and prophylactic treatment. Dr Smith: Your article covers not only the common causes of optic neuritis and, you know, MS, isolated optic neuritis, MOGAD NMO, you talk about a bunch of other things. I wonder, in this patient that we've been discussing, in the absence of any other historical information that seems relevant---or maybe you can define what would seem relevant---would you do other evaluation in that individual, other serologic evaluation and so forth, just in terms of diagnosis? Dr Eggenberger: In that particular case, without other red flags, I don't think I would initially. And follow-up is going to give you a lot of this context. So, you'd be on the lookout for other systemic conditions. So, if the patient had some arthropathy, if the patient had any pulmonary disease hints, if there was anything else that could lead you on a broader expedition. But I think in the context of this case, acutely in the ER, I probably wouldn't do a big lab plug for this. I probably would kind of go down the most likely road and start our treatments, and then follow that patient up. Dr Smith: Yeah, I know your article does a really great job, I think, of outlining when do you need to think about some of these less common causes. Well, can we talk about treatment, Eric? Because I want to move on to some other things. But- so, we've got a patient with isolated optic neuritis, nothing else, you know, in terms of the other antibodies we've talked about. What state-of-the-care- or, state-of-the-art treatment for that patient? Dr Eggenberger: So, the acute treatment for these inflammatory, optic neuritis-type cases is very similar Initially. High dose steroids remains kind of the standard. And then, in MS-related optic neuritis, we may or may not see a taper. So many times it's just an acute treatment of three to five days high dose. Whether that's oral or PO, we could institute either depending on the particular case. And then the taper would depend on the potential cause. So, for instance, with these antibody-driven diseases---so with MOG- or particularly with aquaporin-4---if it's a longitudinally extensive region of optic nerve involved, we tend to use a longitudinally extensive taper. And so, we use prednisone in those cases for several months while we're getting everything else set and deciding what the overall course is going to bring. Dr Smith: What about IV versus oral? There must be something about my practice. I was telling this to Lindsey. Every time on our hospital service, we seem to have at least two patients with optic neuropathies, which I always enjoy, but I find it's a little weird to admit someone who's doing just fine otherwise to the hospital with three days of IV SOLU-MEDROL. So, I'm always trying to figure out, like, how can I get this patient home? And your article had the best term I've heard in a long time, which is “SOLU smoothies.” I mean, are there other strategies that you sometimes use, other than just high-dose IV methylprednisolone? Dr Eggenberger: So, I agree with you. It's sometimes hard to admit somebody for just an IV therapy. And we'll do this as an outpatient, high-dose IV, but we'll also use high-dose orals. And in times in the past when there's been methylprednisolone shortage, we've used high-dose oral or IV dexamethasone as well. I think the IV form, although it's the gold standard, the high-dose oral forms have pretty equivalent bioavailability and are pretty tolerable in my experience. And certainly more convenient. Dr Smith: I wonder if we should switch and maybe talk a little bit about aquaporin-4, I mean, you emphasized that this is a vicious disease---I love the way you describe that---and often blinding. What updates do you have in terms of our therapeutic approach to NMO? That's been rapidly evolving of late. Dr Eggenberger: Right, so these are cases we're always going to share with neuroimmunology. And it requires kind of a multidisciplinary approach, in my opinion, for ideal or for best outcomes. And so, all of these patients are going to get put on prophylactic medications. So, this is a disease you just can't leave untreated. Bad stuff will happen for sure. And we now, fortunately, have some approved, FDA-approved medications that can positively impact the course of this disease. So, that's been a welcome addition. Dr Smith: What are the FDA-approved medications at this point for NMO? Dr Eggenberger: So, there are several at this point, and this is an area that's in growth, fortunately. And again, these are cases we're going to be sharing with our neuroimmunology colleagues. So, these are IV medications typically aimed at complement or CD19. And they all are relatively effective at quieting the course of the disease. Dr Smith: Maybe we can talk a little bit about MOG? I think that most of our listeners are probably pretty familiar with aquaporin-4 and NMO, what- maybe you could describe MOG a little bit and the therapeutic approach for patients with MOG-associated disease? Dr Eggenberger: So, MOG has been a real interesting kind of condition to learn more about. We certainly see a lot of MOG, and I'm sure we saw MOG before it was formally described, but I think we just thought it was kind of a benign, maybe monophasic MS type of presentation. But MOG tends to come in with a loss of acuity that kind of rivals aquaporin-4. So, the acuity tends to be pretty, pretty depressed, but it's very steroid-responsive. So, a lot of times these are the patients, you'll see that their vision will start to improve even when they're on the initial few days of the high-dose steroids. And many times we can get their vision back to 20/20 or very close to that. Dr Smith: And do these patients need chronic management? Dr Eggenberger: So, that's an area of controversy to some degree. About 50% of the optic neuritis MOG-related cases are going to have a relapsing course. And because the disease is steroid-responsive, many times we'll follow these patients after a first attack to see if this is the condition that’s going to declare itself to be relapsing or if this is just going to be a monophasic kind of presentation of optic neuritis. We don't have great biomarkers to separate patients who are going to be in that 50% monophasic course versus the other half. It'll be relapsing. And so, it depends on the patient. If there's somebody that's, as many of these patients are, been very steroid responsive, they get back to 20/20, we can teach them about the disease so that if they do have a relapse, we can get them high-dose steroids in a relatively rapid fashion and they're otherwise healthy, we're probably going to watch that patient. And if it's somebody that doesn't recover 100%, there's other issues with treating them with high-dose steroids potentially in the future, then we may learn more towards an earlier prophylactic approach in that patient. Dr Smith: And what would that approach look like? Is it different from NMO or using more IVIG or B cell depletion as opposed to complement inhibition, for instance? Dr Eggenberger: In MOG, we know that the B cell depletion strategies don't work as well. And so most times we're turning to IVIG, and we found that pretty effective. That's kind of our go-to at this point. Dr Smith: Eric, it's a joy talking to you and I'd love to keep going about content, but I'll refer our listeners to your outstanding article. I mean, you're such a highly regarded neuro-ophthalmologist and educator. I wonder if you could talk to us about why you've done neuro-ophthalmology, and maybe this is an opportunity for you to convince all of our great residents that are listening or students what's great about being a neuro-ophthalmologist. Dr Eggenberger: I think neuro-ophthalmology is by far the most interesting part of neurology. So, it's an area that I think a lot of general neurologists, in my view, don't get enough of in their residency. But it's kind of the essence of neurology, where in neurology you're localizing down to the millimeter and in neuro-ophthalmology, we're localizing down to the micron level. We have several new emerging diseases like these varieties of optic neuritis we're focused on. We're learning lots about those. You get to be involved in lots of different areas of neurology. So, we'll see not just demyelinating conditions, we'll see trauma as it relates to the visual system. And we'll see tumor, and we see all different flavors, stroke, and in any piece of neurology, commonly we'll have some vision aspect that we that we get involved in. So, we see a wide variety of conditions. So, I think it's been a really exciting place to be within neurology. And it's rapidly changing at this point. We're getting new therapeutics. So, it's, I think it's a great time to be a neuro-ophthalmologist. Dr Smith: Yeah, listening to you talk and just reflecting on it, it's really true. Neuro-ophthalmology does cover the entire span of neurology, right? I'm a neuromuscular guy and we see a lot of ocular myasthenia, which is another super exciting area. But we've been talking about optic neuritis, and your article talks about infectious causes and the paraneoplastic and a whole host of things. So, you're a great advocate and salesperson for your field. You convinced me. Dr Eggenberger: Efferent neuro-ophthalmology we love, we could talk about ocular myasthenia and other aspects for another hour. And we get involved in all kinds of cases: third nerve palsies, ocular myasthenia, trauma that involves the efferent system, all different aspects. It's really a great subspecialty, and you get to see a bit of all of neurology. Dr Smith: I'm trying to remember who it was, Eric. It was an attending of mine at medical school. I went to medical school at the Mayo Clinic in Rochester, and I want to say it was Manny Gomez, who was a very famous tuberous sclerosis person, who told me that neuro-ophthalmology was the most elegant specialty within neurology. That stuck with me. Thank you so much for joining me today. I really appreciate it. Dr Eggenberger: Thank you. I appreciate it as well. Dr Smith: So again, today I've been interviewing Dr Eric Eggenberger about his really wonderful article on optic neuritis, which appears in the most recent issue of Continuum on neuro-ophthalmology. Be sure to check out Continuum audio episodes from the... /episode/index/show/continuumjournal/id/35872420

Optic Neuropathies With Dr. Lindsey De Lott 04/16/2025

Optic Neuropathies With Dr. Lindsey De Lott Optic neuropathies encompass all congenital or acquired conditions affecting the optic nerve and are often a harbinger of systemic and central nervous system disorders. A systematic approach to identifying the clinical manifestations of specific optic neuropathies is imperative for directing diagnostic assessments, formulating tailored treatment regimens, and identifying broader central nervous system and systemic disorders. In this episode, Gordon Smith, MD, FAAN speaks with Lindsey De Lott, MD, MS, author of the article “Optic Neuropathies” in the Continuum® April 2025 Neuro-ophthalmology issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. De Lott is an assistant professor of neurology and ophthalmology at the University of Michigan in Ann Arbor, Michigan. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Smith: Hello, this is Dr Gordon Smith. Today I'm interviewing Dr Lindsey De Lott about her article on optic neuropathies, which appears in the April 2025 Continuum issue on neuro-ophthalmology. Lindsey, welcome to the podcast, and perhaps you can introduce yourself to our audience. Dr De Lott: Thank you, Dr Smith. My name is Lindsey De Lott and I am a neurologist and a neuro-ophthalmologist at the University of Michigan. I also serve as the section lead for the Division of Neuro-Ophthalmology, which is actually part of the ophthalmology department rather than the neurology department. And I spend a good portion of my time as a researcher in health services research, and that's now about 60% of my practice or so. Dr Smith: I'm super excited to spend some time talking with you. One, I'm a Michigan person. As we were chatting before this, I trained with Wayne Cornblath and John Trobe, and it's great to have you. I wonder if we maybe can begin- and by the way, your article is outstanding. It is such a huge topic and it was actually really fun to read, so I encourage our listeners to check it out. But you begin by talking about misdiagnosis as being a common problem in this patient population. I wonder if you can talk through why that is and if you have any pearls or pitfalls in avoiding it? Dr De Lott: Yeah, I think there's been a lot of great research looking at misdiagnosis in specific types of optic neuropathies; in particular, compressive optic neuropathies and optic neuritis. A lot of that work has come out of the group at Emory and the group at Washington University. But a lot of neuro-ophthalmologists across the country really contributed to those data. And one of the statistics that always strikes me is that, you know, for example, in patients with optic nerve sheath meningiomas, something like 70% of them are actually misdiagnosed. And a lot of those errors in diagnosis, whether it's for compressive optic neuropathy or some other type of optic neuropathy, really comes down to the way that physicians are really incorporating elements of the history in the physical. For example, in optic neuritis, we know that physicians tend to anchor pretty heavily on pain in general. And that often tends to lead them astray when optic neuritis was never the diagnosis to begin with. So, it's really overindexing on certain things and not paying attention to other features of the physical exam; for example, say presence of an afferent pupillary defect. So, I think it just really highlights the need to have a really relatively structured approach to patients that you think have an optic neuropathy when you're trying to sort of plan your diagnostic testing and your treatment. Dr Smith: I do maybe five or six weeks on our hospital service each year, and I don't know if it's just a Richmond thing, but there's always at least two people in my week who come in with an optic neuropathy or acute vision loss. How common is this in medical practice? Or neurologic practice, I should say? Dr De Lott: Optic neuropathies themselves… if you look across, unfortunately we don't have any great data that puts together all optic neuropathies and gives us an actual sort of prevalence estimate or an incidence estimate from year to year. We do have some of those data for specific types of optic neuropathies like optic neuritis and NAION, and you're probably looking around five-ish per one hundred thousand. So, these aren't that common, but at the same time they do get funneled to- often to emergency rooms and to neurologists from our ophthalmology colleagues and optometry colleagues in particular. Dr Smith: So, one other question I had before kind of diving into the topic at hand is how facile neurologists need to be in recognizing other causes of acute visual loss. I mean, we see acute visual loss as neurologists, we think optic neuropathy, right? Optic neuritis is sort of the go-to in a younger patient, and NAION in someone older. But what do neurologists need to know about other ophthalmologic causes? So, glaucoma or acute retinal disorders, for instance? Dr De Lott: Yeah, I think it's really important that neurologists are able to distinguish optic neuropathies from other causes of vision loss. And so, I would really encourage the listeners to take a look at the excellent article by Nancy Newman about vision loss in this issue where she really kind of breaks it down into vision loss that is acute and chronic and how you really think through distinguishing optic neuropathies from other causes of vision loss. But it is really important. For example, a patient with a central retinal artery occlusion may potentially be eligible for treatments. And that's very different from a patient with optic neuritis and acute vision loss. So, we want to be able to distinguish these things. Dr Smith: So maybe we can pivot to that a little bit. Just for our listeners, our focus today is going to be on- not so much on optic neuritis, although obviously we need to talk a little bit about how we differentiate optic neuritis from non-neuritis optic neuropathies. It seems like the two most common situations we encounter are ischemic optic neuropathies and optic neuritis. Maybe you can talk a little bit about how you distinguish these two? I mean, some of it’s age, some of it’s risk factors, some of it’s exam. What's the framework, of let's say, a fifty-year-old person comes into the emergency room with acute vision loss and you're worried about an optic neuropathy? Dr De Lott: The first step whenever you are considering an optic neuropathy is just making sure that the features are present. I think, really going back to your earlier question, making sure that the patient has the features of an optic neuropathy that we expect. So, it's not only vision loss, but it's also the presence of an apparent pupillary defect in a patient with a unilateral optic neuropathy. In a person who has a bilateral optic neuropathy, that apparent pupillary defect may not be present because it is relative. So, you really would have to have asymmetric vision loss between the two eyes. They should also have impairment of their color vision, and they're probably going to have some kind of visual field defect, whether that's central scotoma or an arcuate scotoma or an altitudinal defect that really respects the horizontal meridian. So, you want to make sure that, first and foremost, you've got a patient that really meets most of those- most of those features. And then from there, we're looking at the other features on their history. How acute is the onset of the vision loss? What is the progression over time? Is there pain associated or not associated with the vision loss? What other medical issues does the patient have? And you know, one of the things you already brought up, for example, is, what's the age of the patient? So, I'm going to be much more hesitant to make a diagnosis of optic neuritis in a much older patient or a diagnosis on the other side, of ischemic optic neuropathy, in a much younger patient, unless they have really clear features that push me in that direction. Dr Smith: I wonder if maybe you could talk a little bit about features that would push you away from optic neuritis, because, I mean, people who are over fifty do get optic neuritis- Dr De Lott: They do. Dr Smith: -and people who get ischemic optic neuropathies who are younger. So, what features would push you away from optic neuritis and towards… let's be broad, just a different type of optic neuropathy? Dr De Lott: Sure. We know that most patients with optic neuritis do have pain, but that pain is accompanied---within a few days, typically---with vision loss. So, pain alone going on for a number of days without any visual symptoms or any of those other things I listed, like the afferent papillary defect, the visual field defect, would push me away from optic neuritis. But in general, yes, most optic neuritis is indeed painful. So, the presence of optic disc edema is unfortunately one of those things that an optic neuritis may be present, may not be present, but in somebody with ischemia that is anterior---and that's the most common type of ischemic optic neuropathy, would be anterior ischemic optic neuropathy---they have to have optic disc edema for us to be able to make that diagnosis, and that is a diagnosis of NAION, or nonarteritic ischemic optic neuropathy. An APD in this case, again, that's just a feature of an optic neuropathy. It doesn't really help you to distinguish, individual field defects are going to be relatively similar between them. So then in patients, I'm also looking, like I said, at their history. So, in a patient where I'm entertaining a diagnosis of ischemic optic neuropathy, I want to make sure that they have vascular risk factors or that I'm actually doing things like measuring their blood pressure in the office if they haven't seen a physician recently or checking a lipid panel, hemoglobin A1c, those kinds of things, to look for vascular risk factors. One of the other features on exam that might push me more- again, in a patient with ischemic optic neuropathy, where it might suggest ischemia over optic neuritis, would be some other features on exam like a crowded optic disc that we sometimes will see in patients with ischemic optic neuropathy. I feel like that was a bit of a convoluted answer. Dr Smith: I thought that was a great answer. And when you say crowded optic disc, that's the- is that the “disc at risk”? Dr De Lott: That is the “disk at risk,” yes. So, crowded optic disk is really a disk that is smaller than what we see in the average population, and the average cup to disk ratio is 0.3. So, I think that's where 30% of the disk should be. So, this extra wiggle room, as I sometimes will explain to my patients. Dr Smith: And then, I wonder if you could talk a little bit about more- just more about exam, right? You raised the importance of recognizing optic disc edema. Are there aspects of that disc edema that really steer you away from optic neuritis and towards ischemia-like hemorrhages or whatnot? And then a similar question about the importance of careful visual field testing? Dr De Lott: So, on the whole, optic disc edema is optic disc edema. And you can have very severe optic neuritis with hemorrhages, cotton wool spots, which is essentially just an infarction of the retinal nerve fiber layer either overlying the disc or other parts of the retina. And ischemia, you can have some of the same features. In patients who have giant cell arteritis, which is just one form of anterior ischemic optic neuropathy, patients can have a pallid optic disc edema where the optic disc is swollen and white-looking. But on the whole, swelling is swelling. So, I would caution anyone against using the features of the optic nerve swelling to make any type of, sort of, definitive kind of diagnosis. It's worth keeping in mind, but I just- I would caution against using specific features, optic nerve swelling. And then for visual field testing, there are certain patterns that sometimes can be helpful. I think as I mentioned earlier, in patients with ischemic optic neuropathy, we’ll often see an altitudinal defect where either the top half or, more commonly, the bottom half of the vision is lost. And that vision loss in the field corresponds to the area of swelling on the disk, which is really rewarding when you're actually able to see sectoral swelling of the disk. So, say the top half of the disk is swollen and you see a really dense inferior defect. And other types of optic neuropathy such as hereditary optic neuropathies, toxic and nutritional optic neuropathies, they often cause more central field loss. And in patients who have optic neuropathies from elevated intracranial pressure, so papilladema, those folks often have more subtle visual field loss in an arcuate pattern. And it's only once the optic nerves have sustained a pretty significant injury that you start to see other patterns of field loss and actual decline in visual acuity in those patients. I do think a detailed visual field assessment can often be pretty helpful as an adjunct to the rest of the exam. Dr Smith: So, we haven't talked a lot about neuroimaging, and obviously, neuroimaging is really important in patients who have optic neuritis. But how about an older patient in whom you suspect ischemic optic neuropathy? Do those patients all need a MRI scan? And if so, is it orbits and brain? How do you- how do you protocol it? Dr De Lott: You're asking such a good question, totally controversial in in some ways. And so, in patients with ischemic optic neuropathy, if you are confident in your diagnosis: the patient is over the age of fifty, they have all the vascular, you know, they have vascular risk factors. And those vascular risk factors are things like diabetes, hypertension, high blood pressure, hyperlipidemia, obstructive sleep apnea. They have a “disc at risk” in the fellow eye. They don't have pain, they don't have a cancer history. Then doing an MRI of the orbits is probably not necessary to rule out another cause. But if you aren't confident that you have all of those features, then you should absolutely do an MRI of the orbit. The MRI of the brain probably doesn't provide you with much additional information. However, if you are trying to distinguish between an ischemic optic neuropathy and, say, maybe an optic neuritis, in those patients we do recommend MRI orbits and brain imaging because the brain does provide additional information about other CNS demyelinating disorders that might be actually the cause of a patient's optic neuritis. Dr Smith: I wonder if you could talk a little bit about posterior ischemic optic neuropathy. That's much less common, and you mentioned earlier that those patients don't have optic disk edema. So, if there's a patient who has vision loss that- in a similar sort of clinical scenario that you talked about, how do you approach that and under what circumstances do we see patients who have posterior ischemic optic neuropathy? Dr De Lott: So, you're going to most often see patients with posterior ischemic optic neuropathy who, for example, have undergone a recent surgery. These are often associated with things like spinal surgeries, cardiac surgeries. And there are a number of risk factors that are associated with it. Things like blood pressure, drain surgery, the amount of blood loss, positioning of patient. And this is something that the surgeons and anesthesiologists are very sensitive to at this point in time, and many patients are often- this can be part of the normal informed consent process at this point in time since this is something that is well-recognized for specific surgeries. In those patients, though… again, unless you're really certain, for example, maybe the inpatient neurology attending and you've been asked to consult on a patient and it's very clear that they went into surgery normal, they came out of surgery with vision loss, and all the rest of the features really seem to be present. I would recommend that in those cases you think about orbital imaging, making sure you're not missing anything else. Again, unless all of the features really are present- and I think that's one of the themes, definitely, throughout this article, is really the importance of neuroimaging in helping us to distinguish between different types of optic neuropathy. Dr Smith: Yeah, I think one of the things that Eric Eggenberger talks about in his article is the need to use precise nomenclature too, which I plan on talking to him about. But I think having this very structured approach- and your article does it very well, I’ll tell our listeners who haven't seen it there's a series of really great tables in the article that outline a lot of these. I wonder, Lindsey, if we can switch to talk about arteritic optic neuropathy. Is that okay? Dr De Lott: Sure. Yeah, absolutely. Dr Smith: How do you sort that out in an older patient who comes in with an ischemic optic neuropathy? Dr De Lott: Yeah. In patients who are over the age of fifty with an ischemic optic neuropathy, we always need to be thinking about giant cell arteritis. It is really a diagnosis we cannot afford to miss. If we do miss it, unfortunately, patients are likely to lose vision in their fellow eye about 1/3 to 1/2 the time. So, it is really one of those emergencies in neuro-ophthalmology and neurology. And so you want to do a thorough review systems for giant cell arteritis symptoms, things like headache, jaw claudication, myalgias, unintentional weight loss, fevers, things of that nature. You also want to check their inflammatory markers to look for evidence of an elevated ESR, elevated C-reactive protein. And then on exam, what you're going to find is that it can cause an anterior ischemic optic neuropathy, as I mentioned earlier. It can cause palette optic disc swelling. But giant cell arteritis can also cause posterior ischemic optic neuropathy. And so, it can be present without any swelling of the optic disc. And in fact, you know, you mentioned one of my mentors, John Trobe, who used to say that in a patient where you're entertaining the idea of posterior ischemic optic neuropathy, who is over the age of fifty with no optic disc swelling, you should be thinking about number one, giant cell arteritis; number two, giant cell arteritis; number three, giant cell arteritis. And so, I think that is a real take-home point is making sure that you're thinking of this diagnosis often in our patients who are over the age of fifty, have to rule it out. Dr Smith: I'll ask maybe a simple question. And presumably just about everyone who you see with a presumed ischemic optic neuropathy, even if they don't have clinical features, you at least check a sed rate. Is that true? Dr De Lott: I do. So, I do routinely check sedimentation rate and C-reactive protein. So, you need to check both. And the reason is that there are some patients who have a positive C-reactive protein but a normal sedimentation rate, so. And vice versa, although that is less common. And so both need to be checked. One other lab that sometimes can be helpful is looking at their CBC. You'll often find these patients with giant cell arteritis have elevated platelet counts. And if you can trend them over time, if you... /episode/index/show/continuumjournal/id/35872390

Approach to Vision Loss With Dr. Nancy Newman 04/09/2025

Approach to Vision Loss With Dr. Nancy Newman Diagnosing and differentiating among the many possible localizations and causes of vision loss is an essential skill for neurologists. The approach to vision loss should include a history and examination geared toward localization, followed by a differential diagnosis based on the likely location of the pathophysiologic process. In this episode, Aaron Berkowitz, MD, PhD, FAAN speaks with Nancy J. Newman, MD, FAAN, author of the article “Approach to Vision Loss” in the Continuum® April 2025 Neuro-ophthalmology issue. Dr. Berkowitz is a Continuum® Audio interviewer and a professor of neurology at the University of California San Francisco in the Department of Neurology and a neurohospitalist, general neurologist, and clinician educator at the San Francisco VA Medical Center at the San Francisco General Hospital in San Francisco, California. Dr. Newman is a professor of ophthalmology and neurology at the Emory University School of Medicine in Atlanta, Georgia. Additional Resources Read the article: Subscribe to Continuum®: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Berkowitz: This is Dr Aaron Berkowitz, and today I'm interviewing Dr Nancy Newman about her article on the approach to visual loss, which she wrote with Dr Valerie Biousse. This article appears in the April 2025 Continuum issue on neuro-ophthalmology. Welcome to the podcast, Dr Newman. I know you need no introduction, but if you wouldn't mind introducing yourself to our listeners. Dr Newman: Sure. My name's Nancy Newman. I am a neurologist and neuro-ophthalmologist, professor of ophthalmology and neurology at the Emory University School of Medicine in Atlanta, Georgia. Dr Berkowitz: You and your colleague Dr Biousse have written a comprehensive and practical article on the approach to visual loss here. It's fantastic to have this article by two of the world's leading experts and best-known teachers in neuro-ophthalmology. And so, readers of this article will find extremely helpful flow charts, tables and very nuanced clinical discussion about how to make a bedside diagnosis of the cause of visual loss based on the history exam and ancillary testing. We'll talk today about that important topic, and excited to learn from you and for our listeners to learn from you. To begin, let's start broad. Let's say you have a patient presenting with visual loss. What's your framework for the approach to this common chief concern that has such a broad differential diagnosis of localizations and of causes? Where do you start when you hear of visual loss? How do you think about this chief concern? Dr Newman: Well, it's very fun because this is the heart of being a neurologist, isn't it? Nowhere in the nervous system is localization as important as the complaint of vision loss. And so, the key, as any neurologist knows, is to first of all figure out where the problem is. And then you can figure out what it is based on the where, because that will limit the number of possibilities. So, the visual system is quite beautiful in that regard because you really can exquisitely localize based on figuring out where things are. And that starts with the history and then goes to the exam, in particular the first localization. So, you can whittle it down to the more power-for-your-buck question is, is the vision lost in one eye or in two eyes? Because if the vision loss clearly, whether it's transient or persistent, is in only one eye, then you only have to think about the eyeball and the optic nerve on that side. So, think about that. Why would you ever get a brain MRI? I know I'm jumping ahead here, but this is the importance of localization. Because what you really want to know, once you know for sure it's in one eye, is, is it an eyeball problem---which could be anything from the cornea, the lens, the vitreous, the retina---or is it an optic nerve problem? The only caveat is that every once in a while, although we trust our patients, a patient may insist that a homonymous hemianopia, especially when it's transient, is only in the eye with the temporal defect. So that's the only caveat. But if it's in only one eye, it has to be in that side eyeball or optic nerve. And if it's in two eyes, it's either in both eyeballs or optic nerves, or it's chiasmal or retrochiasmal. So that's the initial approach and everything about the history should first be guided by that. Then you can move on to the more nuanced questions that help you with the whats. Once you have your where, you can then figure out what the whats are that fit that particular where. Dr Berkowitz: Fantastic. And your article with Dr Biousse has this very helpful framework, which you alluded to there, that first we figure out, is it monocular or binocular? And we figure out if it's a transient or fixed or permanent deficit. So, you have transient monocular, transient binocular, fixed monocular, fixed binocular. And I encourage our listeners to seek out this article where you have a table for each of those, a flow chart for each of those, that are definitely things people want to have printed out and at their desk or on their phone to use at the bedside. Very helpful. So, we won't be able to go through all of those different clinical presentations in this interview, but let's focus on monocular visual loss. As you just mentioned, this can be an eye problem or an optic nerve problem. So, this could be an ophthalmologic problem or a neurologic problem, right? And sometimes this can be hard to distinguish. So, you mentioned the importance of the history. When you hear a monocular visual loss- and with the caveat, I said you're convinced that this is a monocular visual problem and not a visual field defect that may appear. So, the patient has a monocular deficit, how do you approach the history at trying to get at whether this is an eye problem or an optic nerve problem and what the cause may be? Dr Newman: Absolutely. So, the history at that point tends not to be as helpful as the examination. My mentor used to say if you haven't figured out the answer to the problem after your history, you're in trouble, because that 90% of it is history and 10% is the exam. In the visual system, the exam actually may have even more importance than anywhere else in the neurologic examination. And we need as neurologists to not have too much hubris in this. Because there's a whole specialty on the eyeball. And the ophthalmologists, although a lot of their training is surgical training that that we don't need to have, they also have a lot of expertise in recognizing when it's not a neurologic problem, when it's not an optic neuropathy. And they have all sorts of toys and equipment that can very much help them with that. And as neurologists, we tend not to be as versed in what those toys are and how to use them. So, we have to do what we can do. Your directive thalmoscope, I wouldn't throw it in the garbage, because it's actually helpful to look at the eyeball itself, not just the back of the eye, the optic nerve and retina. And we'll come back to that, but we have in our armamentarium things we can do as neurologists without having an eye doctor's office. These include things like visual acuity and color vision, confrontation, visual fields. Although again, you have to be very humble. Sometimes you're lucky; 30% of the time it's going to show you a defect. It has to be pretty big to pick it up on confrontation fields. And then as we say, looking at the fundus. And you probably know that myself and Dr Biousse have been on somewhat of a crusade to allow the emperor's new clothes to be recognized, which is- most neurologists aren't very comfortable using the direct ophthalmoscope and aren't so comfortable, even if they can use it, seeing what they need to see. It's hard. It's really, really hard. And it's particularly hard without pupillary dilation. And technology has allowed us now with non-mydriatic cameras, cameras that are incredible, even through a small pupil can take magnificent pictures of the back of the eye. And who wouldn't rather have that? And as their cost and availability- the cost goes down and their availability goes up. These cameras should be part of every neurology office and every emergency department. And this isn't futuristic. This is happening already and will continue to happen. But over the next five years or so… well, we're transitioning into that. I think knowing what you can do with the direct ophthalmoscope is important. First of all, if you dial in plus lenses, you can't be an ophthalmologist, but you can see media opacities. If you can't see into the back of the eye, that may be the reason the patient can't see out. And then just seeing if someone has central vision loss in one eye, it's got to be localized either to the media in the axis of vision; or it's in the macula, the very center of the retina; or it's in the optic nerve. So, if you get good at looking at the optic nerve and then try to curb your excitement when you saw it and actually move a little temporally and take a look at the macula, you're looking at the two areas. Again, a lot of ophthalmologists these days don't do much looking with the naked eye. They actually do photography, and they do what's called OCT, optical coherence tomography, which especially for maculopathies, problems in the macula are showing us the pathology so beautifully, things that used to be considered subtle like central serous retinopathy and other macula. So, I think having a real healthy respect for what an eye care provider can do for you to help screen away the ophthalmic causes, it's very, very important to have a patient complaining of central vision loss, even if they have a diagnosis like multiple sclerosis, you expect that they might have an optic neuritis… they can have retinal detachments and other things also. And so, I think every one of these patients should be seen by an eye care provider as well. Dr Berkowitz: Thank you for that overview. And I feel certainly as guilty as charged here as one of many neurologists, I imagine, who wish we were much better and more comfortable with fundoscopy and being confident on what we see. But as you said, it's hard with the direct ophthalmoscope and a non-dilated exam. And it's great that, as you said, these fundus photography techniques and tools are becoming more widely available so that we can get a good look at the fundus. And then we're going to have to learn a lot more about how to interpret those images, right? If we haven't been so confident in our ability to see the fundus and analyze some of the subtle abnormalities that you and your colleagues and our ophthalmology colleagues are more familiar with. So, I appreciate you acknowledging that. And I'm glad to hear that coming down the pipeline, there are going to be some tools to help us there. So, you mentioned some of the things you do at the bedside to try to distinguish between eye and optic nerve. Could you go into those in a little bit more detail here? How do you check the visual fields? For example, some people count fingers, some people wiggle fingers, see when the patient can see. How should we be checking visual fields? And what are some of the other bedside tasks you use to decide this is probably going to end up being in the optic nerve or this seems more like an eye? Dr Newman: Of course. Again, central visual acuity is very important. If somebody is older than fifty, they clearly will need some form of reading glasses. So, keeping a set of plus three glasses from cheapo drugstore in your pocket is very helpful. Have them put on their glasses and have them read an ear card. It's one of the few things you can actually measure and examine. And so that's important. The strongest reflex in the body and I can have it duke it out with the peripheral neurologists if they want to, it's not the knee jerk, it's looking for a relative afferent pupillary defect. Extremely important for neurologists to feel comfortable with that. Remember, you cut an optic nerve, you're not going to have anisocoria. It's not going to cause a big pupil. The pupils are always equal because this is not an efferent problem, it's an afferent problem, an input problem. So basically, if the eye has been injured in the optic nerve and it can't get that information about light back into the brain, well, the endoresfol nuclei, both of them are going to reset at a bigger size. And then when you swing over and shine that light in the good optic nerve, the good eye, then the brain gets all this light and both endoresfol nuclei equally set those pupils back at a smaller size. So that's the test for the relative afferent pupillary defect. When you swing back and forth. Of course, when the light falls on the eye, that's not transmitting light as well to the brain, you're going to see the pupil dilate up. But it's not that that pupil is dilating alone. They both are getting bigger. It's an extremely powerful reflex for a unilateral or asymmetric bilateral optic neuropathy. But what you have to remember, extremely important, is, where does our optic nerve come from? Well, it comes from the retinal ganglion cells. It's the axons of the retinal ganglion cells, which is in the inner retina. And therefore inner retinal disorders such as central retinal artery occlusion, ophthalmic artery occlusion, branch retinal artery occlusion, they will also give a relative afferent pupillary defect because you're affecting the source. And this is extremely important. A retinal detachment will give a relative afferent pupillary defect. So, you can't just assume that it's optic nerve. Luckily for us, those things that also give a relative afferent pupillary defect from a retinal problem cause really bad-looking retinal disease. And you should be able to see it with your direct ophthalmoscope. And if you can't, you definitely will be able to see it with a picture, a photograph, or having an ophthalmologist or optometrist take a look for you. That's really the bedside. You mentioned confrontation visual fields. I still do them, but I am very, very aware that they are not very sensitive. And I have an extremely low threshold to- again, I have something in my office. But if I were a general neurologist, to partner with an eye care specialist who has an automated visual field perimeter in their office because it is much more likely to pick up a deficit. Confrontation fields. Just remember, one eye at a time. Never two eyes at the same time. They overlap with each other. You're going to miss something if you do two eyes open, so one eye at a time. You check their field against your field, so you better be sure your field in that eye is normal. You probably ought to have an automated perimetry test yourself at some point during your career if you're doing that. And remember that the central thirty degrees is subserved by 90% of our fibers neurologically, so really just testing in the four quadrants around fixation within the central 30% is sufficient. You can present fingers, you don't have to wiggle in the periphery unless you want to pick up a retinal detachment. Dr Berkowitz: You mentioned perimetry. You've also mentioned ocular coherence tomography, OCT, other tests. Sometimes we think about it in these cases, is MRI one of the orbits? When do you decide to pursue one or more of those tests based on your history and exam? Dr Newman: So again, it sort of depends on what's available to you, right? Most neurologists don't have a perimeter and don't have an OCT machine. I think if you're worried that you have an optic neuropathy, since we're just speaking about monocular vision loss at this point, again, these are tests that you should get at an office of an eye care specialist if you can. OCT is very helpful specifically in investigating for a macular cause of central vision loss as opposed to an optic nerve cause. It's very, very good at picking up macular problems that would be bad enough to cause a vision problem. In addition, it can give you a look at the thickness of the axons that are about to become the optic nerve. We call it the peripapillary retinal nerve fiber layer. And it actually can look at the thickness of the layer of the retinal ganglion cells without any axons on them in that central area because the axons, the nerve fiber layer, bends away from central vision. So, we can see the best we can see. And remember these are anatomical measurements. So, they will lag, for the ganglion cell layer, three to four weeks behind an injury, and for the retinal nerve fiber, layer usually about six weeks behind an entry. Whereas the functional measurements, such as visual acuity, color vision, visual fields, will be immediate on an injury. So, it's that combination of function and anatomy examination that makes you all-powerful. You're very much helped by the two together and understanding where one will be more helpful than the other. Dr Berkowitz: Let's say we've gotten to the optic nerve as our localization. Many people jump to the assumption it's the optic nerve, it's optic neuritis, because maybe that's the most common diagnosis we learn in medical school. And of course, we have to sometimes, when we're teaching our students or trainees, say, well, actually, not all optic nerve disease, optic neuritis, we have to remember there's a broader bucket of optic neuropathy. And I remember, probably I didn't hear that term until residency and thought, oh, that's right. I learned optic neuritis. Didn't really learn any of the other causes of optic nerve pathology in medical school. And so, you sort of assume that's the only one. And so you realize, no, optic neuropathy has a differential diagnosis beyond optic neuritis. Neuritis is a common cause. So how do you think about the “what” once you've localized to the optic nerve, how do you think about that? Figure out what the cause of the optic neuropathy is? Dr Newman: Absolutely. And we've been trying to convince neuro-radiologists when they see evidence of optic nerve T2 hyperintensity, that just means damage to the optic nerve from any cause. It's just old damage, and they should not put in their read consistent with optic neuritis. But that's a pet peeve. Anyway, yes, the piece of tissue called the optic nerve can be affected by any category of pathophysiology of disease. And I always suggest that you run your categories in your head so you don't leave one out. Some are going to be more common to be bilateral involvement like toxic or metabolic causes. Others will be more likely unilateral. And so, you just run those guys. So, in my mind, my categories always are compressive-slash-infiltrative, which can be neoplastic or non-neoplastic. For example, an ophthalmic artery aneurysm pressing on an optic nerve, or a thyroid, an enlarged thyroid eye muscle pressing on the optic nerve. So, I have compressive infiltrative, which could be neoplastic or not neoplastic. I have inflammatory, which can be infectious. Some of the ones that can involve the optic nerve are syphilis, cat scratch disease. Or noninfectious, and these are usually your autoimmune such as idiopathic optic neuritis associated with multiple sclerosis, or MOG, or NMO, or even sarcoidosis and inflammation. Next category for me would be vascular, and you can have arterial versus venous in the optic nerve, probably all arterial if we're talking about... /episode/index/show/continuumjournal/id/35872305

April 2025 Neuro-ophthalmology Issue With Dr. Valérie Biousse 04/02/2025

April 2025 Neuro-ophthalmology Issue With Dr. Valérie Biousse In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Valérie Biousse, MD, who served as the guest editor of the Continuum® April 2025 Epilepsy issue. They provide a preview of the issue, which publishes on April 3, 2025. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Biousse is a professor in the departments of neurology and ophthalmology, as well as the Reunette Harris Chair of Ophthalmic Research, at Emory University in Atlanta, Georgia. Additional Resources Read the issue: Subscribe to Continuum®: More about the American Academy of Neurology: Social Media Host: Guest: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about subscribing to the journal, listening to verbatim recordings of the articles, and exclusive access to interviews not featured on the podcast. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today, I'm interviewing Dr Valerie Biousse, who recently served as Continuum's guest editor for our latest issue on neuro-ophthalmology. Dr Biousse is a professor in the departments of neurology and ophthalmology at Emory University in Atlanta, Georgia where she's also the Renette Harris Chair of Ophthalmic Research. Dr Biousse, welcome and thank you for joining us today. Why don't you introduce yourself to our listeners? Dr Biousse: In addition to what you just mentioned, I would like to highlight that I have a French accent because I was born and raised and went to medical school in France in Saint Pete Pierre, where I trained as a neurologist. And I even practiced as a stroke neurologist and a headache specialist in the big university in Paris before I decided to move to the US to pursue my passion, which was really neuro-ophthalmology. And at the time, it was impossible to get a license in the US, so I had to repeat a residency and became an ophthalmologist. And this is what led me where I am today. Dr Jones: We're fortunate that you did that. I'm glad you did all that extra work because your contributions to the field have obviously been magnificent, especially this issue, which I think is an incredibly important topic for neurologists. This is why we include it in the rotation of Continuum topics. We all know the saying that the eyes are the windows to the soul, but for neurologists they are also the windows to the brain. The only part of the CNS that's visible to us is the optic disc. I think in spite of that, I think neurologists, our readers and our listeners would acknowledge the importance of the ophthalmic exam and respect the importance of that aspect of the neurologic exam. It's an area that feels challenging to us, and many of us, even with lots of years of experience, don't always feel very comfortable with this. So, it's a really important topic and I'm glad you have edited this. And let's start off with, you know, as you've reviewed all these articles from, really, the pinnacle experts in their specific topics in neuro-ophthalmology, as you were editing this issue, Dr Biousse, what would you say is the one biggest, most important practice-changing message about neuro-ophthalmology you would want to convey to our listeners? Dr Biousse: I think its technology, advances in technology. Without any doubt. The ophthalmology world cannot evaluate a patient anymore without access to fundus photography, optical coherence tomography (OCT) of the back of the eye, not just the optic nerve, but the retina. These advantages in technology have completely changed the way we practice ophthalmology. The same applies to neuro-ophthalmology. And these techniques can really help neurologists do a basic eye exam. Dr Jones: So, let's get right into that. And I'm glad you started with that because I still feel, even though I've done it thousands of times, I still feel a little fumbly and awkward when I'm trying to examine and fundus through an undilated pupil, right? And so, this is I think where technology has helped us quantitate with, as you mentioned, OCT, but I think from an accessibility perspective, I think nonmydriatic fundus photography is a very interesting tool for neurologists and non-neurologists. Tell us how, how does that work and how could neurologists implement that in their practice? Dr Biousse: It's a very important tool that of course neurology should be able to use every day. You can take fundus photographs of the back of the eye without dilating the pupil. The quality of the photographs is usually very good. You only have access to what we call the posterior pole of the eye, so the optic nerves and the macula and the vascular arcade. You don't see the periphery of the retina, but in neuro-ophthalmology or neurology you don't need access to the periphery of the retina, so it doesn't matter. What is remarkable nowadays is that we have access to very highly performing fundus cameras which can take pictures through very, very small pupils or in patients of all ages. You can use it on a two-year-old in a pediatric clinic. You can use it on a much older person who may have a cataract or other eye problems. And what's really new and what this issue highlights is that it's not just that we can take pictures of the back of the eye, we can also perform OCT at the same time using the same camera. So, that's really a complete game changer for neurologists. Dr Jones: And that's extremely helpful. If I'm in a neurology clinic and I would like to use this technology, how would I access that? Do I need special equipment? Can I use my smartphone and an app? How would that work in terms of getting the image but also getting an interpretation of it? Dr Biousse: It all depends on what your ultimate goal is. The fundus cameras, they are like regular cameras or like any technology that would allow you to get brain imaging. The more sophisticated, the better the quality of the image, the more expensive they are. You know, that's the difference between a three-tesla MRI and a head CT. You buy a camera that's more expensive, you're going to have access to much easier cameras and to much higher resolution of images, and therefore you're going to be much happier with the results. So, I always tell people be very careful not to get a tool that is not going to give you the quality of images you need or you may make mistakes. You basically have two big sorts of cameras. You have what we call the tabletop cameras, which is a little more bulky camera, a little more expensive camera that's sitting on the table. The table can be on wheels, so you can move the table to the patient or you can move the patient to the table. That's very convenient in a neurology clinic where most patients are outpatient. It works in the emergency department. It's more difficult at bedside in the hospital. Or you can have a handheld camera, which can be sophisticated, a device that just uses a handheld camera or, as you mentioned, a small camera that you place on your smartphone, or even better, a camera that you can attach to some of the marketed direct ophthalmoscopes. In all situations, you need to be able to transfer those images to your electronic medical records so that you can use them. You can do that with all tabletop cameras, most handheld cameras; you cannot do it with your smartphone. So that gives you an idea of what you can use. So yes, you can have a direct ophthalmoscope with a little camera mounted. This is very inexpensive. It is very useful at bedside for the neurologists who do- who see patients every day, or the resident on call. But if you really want to have a reliable tool in clinic, I always recommend that people buy a tabletop camera that's connected to the electronic medical record. Dr Jones: You know, the photos always make it so much more approachable and accessible than the keyhole view that I get with my direct ophthalmoscope in clinic. And obviously the technology and the tools are part of the story, but also, it's access to the expertise. Right? There are not many neuro-ophthalmologists in the world, and getting access to the experts is a challenge, I think, everywhere, everywhere in the world really. When you think about how technology can expand that---and here I'm getting at AI, which I hesitate to bring up because it feels like we talk about AI a lot---are there tools that you think are here now or will be coming soon that will help clinicians, including neurologists, interpret fundus photography or other neuro-ophthalmologic findings, maybe eye movements, to make that interpretation piece a little more accessible? Dr Biousse: Absolutely. It's going to happen. It's not there yet. OK? I always tell people, AI is very important and it's a big part of our future without any doubt. But to use AI you need pictures. To get pictures, you need a camera. And so I tell people, first you start with the camera, you implement the camera, you incorporate the camera in your electronic medical record. Because if you do that, then the pictures become accessible to everyone, including the ophthalmologist who’s maybe offsite and can review the pictures and provide an official interpretation of the pictures to help you. You can also transfer those pictures using secure mode of transfers and not your smartphone text application, which you really don't want to use to transfer medical information. And that's why I insist on the fact that those pictures should definitely appear in the patient's medical record. Otherwise you're going to break HIPAA laws, and that's an issue that comes up quite often. Once you have the pictures in the electronic medical record and once you have the pictures in the camera, you can do three things. You can look at them yourself. And many of my neurology colleagues are very competent at declaring that an optic nerve is normal or an optic nerve is swollen or an optic nerve is pale. And very often that's all we need. You can say, oh, I don't know about that one, and page the ophthalmologist on call, give the patient 's medical record number, have them look at the pictures, provide an interpretation, and that's where you have your answer. And this can be done in real time, live, when you're at bedside, no problem. Or you can use AI as what I call “Diagnostic A.” I always compare it as, imagine if you had a little robot neuro-ophthalmologist in your pocket that you could use at any time by just taking a picture, clicking submit on the AI app. The app will tell you never, it's normal or it's papilledema or it's pale. The app will tell you, the probability of this optic disk of being normal is 99% or the probability that this is papilledema. And when I say papilledema, I mean papilledema from rest intracranial pressure that's incredible as opposed to optic disc edema from an optic neuritis or from an ischemic optic neuropathy. And the app will tell you, the probability that this is papilledema is eighty six percent. The probability that it's normal is zero. The probability that it's another cause of disc edema is whatever. And so, depending on your probability and your brain and your own eyes, because you know how to interpret most fundus photographs, you really can make an immediate diagnosis. So that is not available for clinical use yet because the difficulty with the eye, as you know, is to have it have a deep learning algorithm cleared by the FDA. And that's a real challenge. But many research projects have shown that it can be done. It is very reliable, it works. And we know that such tools can either be either incorporated inside the camera that you use---in which case it's the camera that gives you the answer, which I don't think is the ideal situation because you have one algorithm per camera---or you have the algorithm on the Cloud and your camera immediately transfers in a secure fashion the images to the Cloud and you get your answer that way directly in your electronic medical record. We know it can be done because it happens every day for diabetic retinopathy. Dr Jones: Got it. And so, it'll expand, and obviously there has to be a period of developing trust in it, right? Once it's been validated and it becomes something that people use. And I get the sense that this isn't going to replace the expertise of the people that use these tools or people in neuro-ophthalmology clinics. It really will just augment. Is that a fair statement? Dr Biousse: Absolutely. Similar to what you get when you do an EKG. The EKG machine gives you a tentative interpretation, correct? And when the report is “it's normal,” you really can trust it, it's normal. But when it says it's not normal, this is when you look at it and you ask for a cardiology consultation. That's usually what happens. And so, I really envision such AI tools as, “it's normal,” in which case you don't need a consultation. You don't need to get an ophthalmology consultation to be sure that there is no papilledema in a patient with headache, in a patient with possible cerebrospinal fluid shunt malfunction. You don't need it because if the AI tool tells you it's normal, it's normal. When it's not normal, you still need the expertise of the ophthalmologist or the neuro-ophthalmology. The same applies to the diagnosis of eye movement. So that's a little more difficult to implement because, as you know, to have an AI algorithm, you need to have trained the algorithm with many examples. We have many examples of pathology of the back of the eyes, because that's what we do. We take pictures every day and there are databases of pictures, there are banks of pictures. But how many examples do we have of abnormal line movement in myasthenia, of videos or downbeat nystagmus? You know, even if we pulled all our collections together, we would come up with what, two hundred examples of downbeat nystagmus around the world? That's not enough to train an AI system, and that's why most of the research on eye movement right now is devoted to creating algorithm that mimic abnormal eye movements so that we can make them and then train algorithm which job will be to diagnose the abnormal eye movement. There's an extra difficult step, it's actually quite interesting. But it's going to happen. You would be able to have the patient look at the camera on the computer and get a report about “it’s normal” or “the saccades, whatever, are not normal. It's most likely an internucleosomal neuralgia” or “it is downbeat nystagmus.” And that's not, again, science fiction. There are very good groups right now working on this. Dr Jones: That's really fascinating, and that- you anticipated my next question, which is, I think neurologists understand the importance of the ocular motor exam from a localizing perspective, but it's also complex and challenging. And I think that's certainly an area of potential growth. And you make a good point that we need some data to train the models. And until we have these tools, Dr Biousse, that will sort of democratize and provide access through technology to diagnosis and, you know, ultimately management of neuro-ophthalmology disorders, we know that there are gaps in the care of these patients right now in the modern day. In your own practice, in your own work at Emory, what do you see as the biggest gap in practice in caring for these patients? Dr Biousse: I think there is a lack of confidence amongst many neurologists regarding their ability to perform a basic eye exam and provide a reliable report of their finding. And the same applies to most ophthalmologists. And that's very interesting because we have, often, a large cohort of patients who are in between the two specialties and are getting a little bit lost. The ophthalmologist doesn't know what to do. The neurologist usually knows what to do, but he's not completely sure that it's the right thing to do. And that's where the neuro-ophthalmologist comes in. And when you have a neuro-ophthalmologist right there, it's fantastic, okay? We bridge the two specialties, and we often just translate what the ophthalmologist said to the neurologist or what the neurologist said to the ophthalmologist and suddenly everything becomes clear. But unfortunately, there are not enough neuro-ophthalmologists. There is a definite patient access issue even when there is a neuro-ophthalmologist because not only is there a coverage heterogeneity in the country and in the world, but then everybody is too busy to be able to see a patient right away. And so, this gap impairs the quality of patient care. And this is why despite all this technology, despite the future, despite AI, we teach ophthalmologists and neurologists how to do a neuro-op examination, how to use it for localization, how to use it to increase the value and the power of a good neurologic examination so that nothing is missed. And I'm taking a very simple example. Neurologists see patients with headaches all the time. The vast majority of those headaches are benign headaches. 90% of headache patients are either migraine or tension headache or analgesic abuse headaches, but they are not secondary headache that are life threatening or neurologically threatening. If the patient has papilledema, it's a huge retina that really should prompt immediate workup, immediate prevention of vision loss with the help of the ophthalmologist. And unfortunately, that's often delayed because the patients with headaches do not see eye doctors. They see their primary care providers who does not examine the back of the eye, and then they reach neurology sometimes too late. And when the neurologist is comfortable with the ophthalmoscope, then the papilledema is identified. But when the neurologist is not comfortable with the ophthalmoscope, then the patient is either misdiagnosed or sent to an eye care provider who makes the diagnosis. But there is always a delay in care. You know, most patients end up with a correct diagnosis because people know what to do. But the problem is the delay in appropriate care in those patients. And that's where technology is a complete life-changing experience. And, you know, I want to highlight that I am not blaming neurologists for not looking at the back of the eye with a direct ophthalmoscope without pharmacologic dilation of the pupil. It is not possible to do that reliably. The first thing I learned when I transitioned from a neurologist to an ophthalmologist is that no eye care provider ever attempts to look at the back of the eyes without dilating the pupils because it's too hard. Why do we ask neurologists to do it? It's really unfair, correct? And then the ophthalmoscope is such an archaic tool that gives only a very small portion of the back of the eye and is extraordinarily difficult to use. It's really not fair. And so, until we give the appropriate tools to neurologists, I don't think we should complain about neurologists not being reliable when they look at the back of the eye. It's a major issue. Dr Jones: I appreciate you giving us some absolution there. I don't think we would ask neurologists to check reflexes but then not give them a reflex hammer, right? So maybe that's the analogy to not dilating the pupil. So, for you and your practice, in our closing minutes here, Dr Biousse, what's the most rewarding thing for you in neuro-ophthalmology? What do you find most rewarding in the care of these patients? Dr Biousse: Well, I think the most rewarding is the specialty itself. I'm a neurologist at heart. This is where my heart belongs. What's great about those neuro-ophthalmology patients is that it is completely unpredictable. They are unpredictable. They can have anything. I am super specialized because I'm a... /episode/index/show/continuumjournal/id/35872285

Diversity and Underserved Patient Populations in Epilepsy With Dr. Dave Clarke 03/26/2025

Diversity and Underserved Patient Populations in Epilepsy With Dr. Dave Clarke Despite advances in epilepsy management, disparities and lack of inclusion of many people with epilepsy are associated with increased morbidity and mortality. Improving awareness and promoting diversity in research participation can advance treatment for underserved populations and improve trust. In this episode, Teshamae Monteith, MD, PhD, FAAN speaks Dave F. Clarke, MBBS, FAES, author of the article “Diversity and Underserved Patient Populations in Epilepsy,” in the Continuum® February 2025 Epilepsy issue. Dr. Monteith is a Continuum® Audio interviewer and an associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida. Dr. Clarke is the Kozmetsky Family Foundation Endowed Chair of Pediatric Epilepsy and Chief or Comprehensive Pediatric Epilepsy Center, Dell Medical School at the University of Texas at Austin in Austin, Texas. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum Journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Monteith: This is Dr Teshamae Monteith. Today I'm interviewing Dr Dave Clarke about his article on diversity and underserved patient populations in epilepsy, which appears in the February 2025 Continuum issue on epilepsy. So why don't you introduce yourself to our audience? Dr Clarke: Sure. My name is Dr Dave Clarke, as alluded to. I'm presently at the University of Texas in Austin, originating from much farther south. I'm from Antigua, but have been here for quite a while working within the field in epilepsy surgery, but more and more getting involved in outreach, access to care, and equity of healthcare in epilepsy. Dr Monteith: And how did you get involved in this kind of work? Dr Clarke: That's an amazing question. You know, I did it in a bit of a inside out fashion. I initially started working in the field and trying to get access to persons in the Caribbean that didn't have any neurological care or investigative studies, but very quickly realized that persons around the corner here in Texas and wherever I’ve worked have had the exact same problems, getting access via fiscal or otherwise epilepsy care, or geographically getting access, with so few having neurologists close at hand. Therefore, I started working both on a regional, national, and it transcended to a global scale. Dr Monteith: Wow, so you're just everywhere. Dr Clarke: Well, building bridges. I've found building bridges and helping with knowledge and garnering knowledge, you can expand your reach without actually moving, which is quite helpful. Dr Monteith: Yeah. So why don't you tell us why you think this work is so important in issues of diversity, underserved populations, and of course, access to epilepsy care? Dr Clarke: Sure, not a problem. And I think every vested person in this can give you a different spiel as to why they think it's important. So, I'll add in a few facts pertaining to access, but also tell you about why I think personally that it's not only important, but it will improve care for all and improve what you believe you could do for a patient. Because the sad thing is to have a good outcome in the United States presently, we have over three hundred epilepsy centers, but they have about eight or nine states that don't have any epilepsy centers at all. And even within states themselves, people have to travel up to eight hours, i.e., in Texas, to get adequate epilepsy care. So that's one layer. Even if you have a epilepsy center around the corner, independent of just long wait times, if you have a particular race or ethnicity, we've found out that wait may be even longer or you may be referred to a general practitioner moreso than being referred to an epilepsy center. Then you add in layers of insurance or lack thereof, which is a big concern regardless of who you are; poverty, which is a big concern; and the layers just keep adding more. Culture, etcetera, etcetera. If you could just break down some of those barriers, it has been shown quite a few years ago that once you get to an epilepsy center, you can negate some of those factors. You can actually reduce time to access and you can improve care. So, that's why I'm so passionate about this, because something could potentially be done about it. Dr Monteith: That's cool. So, it sounds like you have some strategies, some strategies for us. Dr Clarke: Indeed. And you know, this is a growth and this is a learning curve for me and will be for others. But I think on a very local, one-to-one scale, the initial strategy I would suggest is you have to be a good listener. Because we don't know how, when, where or why people are coming to us for their concerns. And in order to judge someone, if they may not have had a follow-up visit or they may not have gotten to us after five medications, the onus may not have been on that person. In other words, as we learned when we were in medical school, history is extremely important, but social history, cultural history, that's also just as important when we're trying to create bridges. The second major thing that we have to learn is we can't do this alone. So, without others collaborating with us outside of even our fields, the social worker who will engage, the community worker who will discuss the translator for language; unless you treat those persons with respect and engage with those persons to help you to mitigate problems, you'll not get very far. And then we'll talk about more, but the last thing I'll say now is they have so many organizations out there, the Institute of Medicine or the International League Against Epilepsy or members of the American Epilepsy Society, that have ways, ideas, papers, and articles that can help guide you as to how better mitigate many of these problems. Dr Monteith: Great. So, you already mentioned a lot of things. What are some things that you feel absolutely the reader should take away in reading your article? You mentioned already listening skills, the importance of interdisciplinary work, including social work, and that there are strategies that we can use to help reduce some of this access issues. But give me some of the essential points and then we'll dive in. Dr Clarke: OK. I think first and foremost we have to lay the foundation in my mind and realize what exactly is happening. If you are Native American, of African descent, Hispanic, Latinx, geographically not in a region where care can be delivered, choosing one time to epilepsy surgery may be delayed twice, three, four times that of someone of white descent. If you are within certain regions in the US where they may have eight, nine, ten, fourteen epilepsy centers, you may get to that center within two to three years. But if you're in an area where they have no centers at all, or you live in the Dakotas, it may be very difficult to get to an individual that could provide that care for you. That's very, very basic. But a few things have happened a few years ago and even more recently that can help. COVID created this groundswell of ambulatory engagement and ambulatory care. I think that can help to mitigate time to get into that person and improving access. In saying that, there are many obstacles to that, but that's what we have to work towards: that virtual engagement and virtual care. That would suggest in some instances to some persons that it will take away the one-to-one care that you may get with persons coming to you. But I guarantee that you will not lose patients because of this, because there's too big a vacuum. Only 22% of persons that should actually get to epilepsy centers actually get to epilepsy centers. So, I think we can start with that foundation, and you can go to the article and learn a lot more about what the problems are. Because if you don't know what the problems are, you can't come up with solutions. Dr Monteith: Just give us a few of the most persistent inequities and epilepsy care? Dr Clarke: Time to seeing a patient, very persistent. And that's both a disparity, a deficiency, and an inequity. And if you allow me, I'll just explain the slight but subtle difference. So, we know that time to surgery in epilepsy in persons that need epilepsy surgery can be as long as seventeen years. That's for everyone, so that's a deficiency in care. I just mentioned that some sociodemographic populations may not get the same care as someone else, and that's a disparity between one versus the other. Health equity, whether it be from NIH or any other definition, suggests that you should get equitable care between one person and the other. And that brings in not only medical, medicolegal or potential bias, that we may have one person versus the other. So, there's a breakdown as to those different layers that may occur. And in that I'm telling you what some of the potential differences are. Dr Monteith: And so, you mentioned, it comes up, race and ethnicity being a major issue as well as some of the geographic factors. How does that impact diagnosis and really trying to care for our patients? Dr Clarke: So again, I'm going to this article or going to, even. prior articles. It has been shown by many, and most recently in New Jersey, that if you're black, Hispanic, Latin- Latinx, it takes you greater than two times the time to surgery. Reduced time to surgery significantly increases morbidity. It potentially increases mortality, as has been shown by a colleague of mine presently in Calgary. And independent of that, we don't look at the other things, the other socially related things. Driving, inability to work, inability to be adequately educated, the stigma related to that in various cultures, various countries. So, that deficit not only increased the probability of having seizures, but we have to look at the umbrella as to what it does. It significantly impacts quality of life of that individual and, actually, the individuals around them. Dr Monteith: So, what are some of these drivers, and how can we address them, or at least identify them, in our clinic? Dr Clarke: That's a question that's rather difficult to answer. And not because there aren't ideas about it, but there’s actually mitigating those ideas or changing those ideas we're just presently trying to do. Although outlines have been given. So, in about 2013, the federal government suggested outlines to improve access and to reduce these inequities. And I'll just give you a few of them. One of those suggestions was related to language and having more improved and readily available translators. Something simple, and that could actually foster discussions and time to better management. Another suggestion was try to train more persons from underserved populations, persons of color. Reason being, it has been shown in the social sciences and it is known in the medical sciences that, if you speak to a person of similar culture, you tend to have a better rapport, you tend to be more compliant, and that track would move forward, and it reduces bias. Now we don't have that presently, and I'm not sure if we'll have that in the near future, although we're trying. So then, within your centers, if you have trainings on cultural sensitivity, or if you have engagements and lectures about how you can engage persons from different populations, those are just some very simple pearls that can improve care. This has been updated several times with the then-Institute of Medicine in 2012, 2013, they came out with, in my mind, a pretty amazing article---but I'm very biased---in which they outline a number of strategic initiatives that could be taken to improve research, improve clinical care, improve health equity through health services research, to move the field forward, and to improve overall care. They updated this in 2020, and it's a part of the 2030 federal initiative not only for epilepsy, but to improve overarching care. All of this is written in bits and pieces and referenced in the article. To add icing on top, the World Health Organization, through advocacy of neurological groups as well as the International League Against Epilepsy and the AES, came out with the Intersectoral Action Plan on Epilepsy and Other Neurological Diseases, which advocates for parallel improvement in overall global care. And the United States have signed on to it, and that have lit a fire to our member organizations like the American Epilepsy Society, American Academy of Neurology, and others, trying to create initiatives to address this here. I started off by saying this was difficult because, you know, we have debated epilepsy care through 1909 when the International League against Epilepsy was founded, and we have continually come up with ways to try and advance care. But this have been the most difficult and critical because there's social dynamics and social history and societal concerns that have negated us moving forward in this direction. But fortunately, I think we're moving in that direction presently. That's my hope. And the main thing we have to do is try to sustain that. Dr Monteith: So, you talked about the importance of these global initiatives, which is huge, and other sectors outside of neurology. Like for example, technology, you spoke about telemedicine. I think you were referring to telemedicine with COVID. What other technologies that are more specific to the field of epilepsy, some of these monitorings that maybe can be done? Dr Clarke: I was just going to just going to jump on that. Thank you so much for asking. Dr Monteith: I have no disclosures in this field. I think it's important and exciting to think how can we increase access and even access to monitoring some of these technologies. That might be expensive, which is another issue, but…. Dr Clarke: So, the main things in epilepsy diagnosis and management: you want to hear from the patient history, you want to see what the seizures look like, and then you want to find ways in which to monitor those seizures. Hearing from the patient, they have these questionnaires that have been out there, and this is local, regional, global, many of them standardized in English and Spanish. Our colleagues in Boston actually created quite a neat one in English and Spanish that some people are using. Ecuador has one. We have created someone- something analogous. And those questionnaires can be sent out virtually and you can retrieve them. But sometimes seeing is believing. So, video uploads of seizures, especially the cell phone, I think has been management-changing for the field of epilepsy. The thing you have to do however, is do that in a HIPAA-compliant way. And several studies are ongoing. In my mind, one of the better studies here was done on the East Coast, but another similar study, to be unnamed, but again, written out in the articles. When you go into these apps, you can actually type in a history and upload a video, but the feed is not only going to you, it may be going to the primary care physician. So, it not only helps in one way in you educating the patient, but you educate that primary care physician and they become extenders and providers. I must add here my colleagues, because we can't do without them. Arguably in some instances, some of the most important persons to refer patients, that's the APPs, the PAs and the nurse practitioners out there, that help to refer patients and share patients with us. So, that's the video uploads they're seeing. But then the other really cool part that we're doing now is the ambulatory world of EEGs. Ceribell, Zeto, to name of few, in which you could potentially put the EEG leads on persons with or without the EEG technologist wirelessly and utilize the clouds to review the EEGs. It's not perfect just yet, but that person that has to travel eight hours away from me, if I could do that and negate that travel when they don't have money to pay for travel or they have some potential legal issues or insurance-related issues and I could read the EEG, discuss with them via telemedicine their care, it actually improves access significantly. I'm going to throw in one small twist that, again, it’s not perfect. We're now trying to monitor via autonomic features, heart rate movement and others, for seizures and alert family members, parents, because although about 100,000 people may be affected with epilepsy, we're talking about 500,000 people who are also affected that are caregivers, affiliates, husbands, wives, etcetera. Just picture it: you have a child, let's say three, four years old and every time they have a seizure- or not every time, but 80% of times when they have a seizure, it alerts you via your watch or it alerts you in your room. It actually gives that child a sense of a bit more freedom. It empowers you to do something about it because you can understand here. It potentially negates significant morbidity. I won't stretch it to say SUDEP, but hopefully the time will come when actually it can prevent not only morbidity, but may prevent death. And I think that's the direction we are going in, to use technology to our benefit, but in a HIPAA-compliant way and in a judicious way in order to make sure that we not only don't overtreat, but at the end of the day, we have the patient as number one, meaning everything is vested towards that patient and do no harm. Dr Monteith: Great. One thing you had mentioned earlier was that there are even some simple approaches, efficiency approaches that we can use to try and optimize care for all in our clinics. Give me what I need to know, or do. Give me what I need to do. Dr Clarke: Yeah, I'll get personal as to what we're trying to do here, if you don't mind. The initial thing we did, we actually audited care and time to care delivery. And then we tried to figure out what we could do to improve that access and time to care, triaging, etcetera. A very, very simple thing that can be done, but you have to look at costs, is to have somebody that actually coordinates getting persons in and out of your center. If you are a neurologist that works in private practice, that could potentially be a nurse being associated directly one-and-one with one of the major centers, a third- or fourth-level center. That coordination is key. Educate your nurses about epilepsy care and what the urgent situations are because it will take away a lot of your headache and your midnight calls because they'll be able to know what to do during the day. Video uploads, as I suggested, regardless of the EMR that you have, figure out a way that a family could potentially send a video to you, because that has significantly helped in reducing investigative studies. Triaging appropriately for us to know what patients we can and cannot see. Extenders has helped me significantly, and that's where I’ll end. So, as stated, they had many neurologists and epileptologists, and utilizing appropriately trained nurse practitioners or residents, engaging with them equally, and/or social workers and coordinators, are very helpful. So hopefully that's just some low-hanging fruit that can be done to improve that care. Dr Monteith: So why don't you give us some... /episode/index/show/continuumjournal/id/34884335

A Multidisciplinary Approach to Nonepileptic Events With Dr. Adriana Bermeo-Ovalle 03/19/2025

A Multidisciplinary Approach to Nonepileptic Events With Dr. Adriana Bermeo-Ovalle Nonepileptic events are prevalent and highly disabling, and multiple pathophysiologic mechanisms for these events have been proposed. Multidisciplinary care teams enable the efficient use of individual expertise at different treatment stages to address presentation, risk factors, and comorbidities. In this episode, Kait Nevel, MD, speaks with Adriana C. Bermeo-Ovalle, MD, an author of the article “A Multidisciplinary Approach to Nonepileptic Events,” in the Continuum® February 2025 Epilepsy issue. Dr. Nevel is a Continuum® Audio interviewer and a neurologist and neuro-oncologist at Indiana University School of Medicine in Indianapolis, Indiana. Dr. Bermeo-Ovalle is a professor and vice-chair for Faculty Affairs in the Department of Neurological Sciences at Rush University Medical Center in Chicago, Illinois. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr. Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum Journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Nevel: Hello, this is Dr Kait Nevel. Today I'm interviewing Dr Adriana Bermeo about her article on a multidisciplinary approach to nonepileptic events, which she wrote with Dr Victor Petron. This article appears in the February 2025 Continuum issue on epilepsy. Welcome to the podcast, and please introduce yourself to our audience. Dr Bermeo-Ovalle: Hello Dr Neville, it's a pleasure to be here. Thank you very much for inviting me. My name is Adriana Bermeo and I'm an adult epileptologist at Rush University Medical Center in Chicago, and I am also the codirector of the NEST clinic, which is a treatment clinic for patients with nonepileptic seizures within our level four epilepsy center. Dr Nevel: Wonderful. Well, thank you so much for being here, and I can't wait to talk to you about your article and learn a little bit about NEST, maybe, during our conversation, and how you approach things. To start us off talking about your article today, could you share with us what you think is the most important takeaway from your article for the practicing neurologist? Dr Bermeo-Ovalle: Wonderful. There's some messages that I would like people to get from working with patients with functional neurologic disorders in general. The first one is that functional neurologic disorders are very common in presentation in the neurologic clinic, almost no matter what your practice of self-specialty care is. The second is that for people who treat patients primarily with seizures or epilepsy, they account for between 5 to 10% of our patients in the clinic, but about 30% of our patients in our epilepsy monitoring unit because the seizures typically do not respond to anti-seizure medication management. Also, that in order to diagnose them, you don't need to have a neuropsychological stress already be available for the patient or the clinician. And the most important thing is that there are available treatments for these patients and that there are options that we can offer them for them to have less seizures and to be more integrated to whatever activities they want to get integrated. Dr Nevel: Wonderful. What do you think a practicing neurologist might find surprising after reading your article? Dr Bermeo-Ovalle: I think still many neurologists feel very hopeless when they see patients with these conditions. They do not have very good answers right away for the patients, which is frustrating for the neurologist. And they don't think there's too much they can do to help them other than send them somewhere else, which is very difficult for the neurologist and is crushing to the patients to see these doctors that they're hoping to find answers to and then just find that there's not much to do. But what I want neurologists to know is that we are making strides in our understanding of the condition and that there are effective treatments available. And I hope that after reading this and engaging with this conversation, they will feel curious, even hopeful when they see the next patient in the clinic. Dr Nevel: Yeah, absolutely. I find the history of nonepileptic seizures really interesting and I enjoyed that part of your article. How has our understanding of nonepileptic seizures evolved over the centuries, and how does our current understanding of nonepileptic seizures inform the terminology that we use? Dr Bermeo-Ovalle: Yeah. The way we name things and the way we offer treatment goes along to how we understand things. So, the functional seizures and epileptic seizures were understood in ancient times as possession from the spirits or the demons or the gods, and then treatments were offered to those kind of influences and that continues to happen with functional seizures. So, we go through the era when this was thought to be a women-only condition that was stemming from their reproductive organs and then treatments accordingly were presented. And later on with Charcot and then Freud, they evolved to even conversion disorders, which is one understanding the most conversion disorders, which is one of the frameworks where this condition has been treated with psychotherapy, psychoanalytic psychotherapy. And in our current understanding, we understand functional neurologic disorders in general as a more like a connection, communication network disorder, between areas of the brain that modulate emotional processing and movement control. And therefore, our approach these days is much more geared towards rehabilitation. You know, I think that's the evolution of thinking in many different areas. And as we learn more, we will be acquiring more tools to help our patients. Dr Nevel: Yeah, great. Thanks so much for that answer. Just reading the historical information that you have in your article, you can imagine a lot of stigma with this diagnosis too over time, and that- I think that that's lessening. But I was wondering if you could talk about that a little bit. How do we approach that with our patients and loved ones, any stigma that they might feel or perceive from being diagnosed with nonepileptic seizures? Dr Bermeo-Ovalle: Thank you for asking that question. Stigma is actually an important problem even for people living with epilepsy. There's still a lot of misunderstanding of what epilepsy is and how it affects people, and that people living with epilepsy can live normal, healthy lives and do everything they want to do with appropriate treatment. And if a stigma is still a problem with epilepsy, it is a huge problem for patients living with functional neurologic symptoms in general, but particularly with functional seizures or nonepileptic seizures. Because the stigma in this population is even perpetuated by the very people who are supposed to help them: physicians, primary care doctors, emergency room doctors. Unfortunately, the new understanding of this condition has not gotten to everybody. And these patients are often even blamed for their symptoms and for the consequences of their symptoms and of their seizures in their family members, in their job environment, in their community. Living with that is really, really crushing, right? Even people talk about, a lot about malingering. They come back about secondary gain. I can tell you the patients I see with functional seizures gain nothing from having this condition. They lose, often, a lot. They lose employment, they lose ability to drive. They lose their agency and their ability to function normally in society. I do think that the fight- the fighting of stigma is one that we should do starting from within, starting from the healthcare community into our understanding of what these patients go through and what is causing their symptoms and what can we do to help them. So there's a lot of good work to be done. Dr Nevel: Absolutely. And it starts, like you said, with educating everybody more about nonepileptic seizures and why this happens. The neurobiology, neurophysiology of it that you outlined so nicely in your article, I'm going to encourage the listeners to look at Figure 1 and 4 for some really nice visualization of these really complex things that we're learning a lot about now. And so, if you don't mind for our listeners, kind of going over some of the neurobiology and neurophysiology of nonepileptic seizures and what we're learning about it. Dr Bermeo-Ovalle: Our understanding of the pathophysiology of functional neurologic seizure disorder is in its infancy at this point. The neurobiological processes that integrate emotional regulation and our responses to it, both to internal stimuli and to external stimuli and how they affect our ability to have control over our movement---it’s actually amazing that we as neurologists know so little about these very complex processes that the brain do, right? And for many of us this is the reason why we're in neurology, right, to be at the forefront of this understanding of our brain. So, this is in that realm. It is interesting what we have learned, but it's amazing all that we have to learn. There is the clear relationship between risk factors. So, we know patients with functional neurologic symptom disorder and with functional seizures, particularly in many different places in the world with many different beliefs, relationship to their body, to their expression of their body, have this condition no matter how different they are. And also, we know that they have commonalities. For example, traumatic experiences that are usually either very strong traumatic experiences or very pervasive traumatic experiences or recurrent over time of different quality. So, we are in the process of understanding how these traumatic experiences actually inform brain connectivity and brain development that result in this lack of connections between brain areas and the expression of them, and that result in this kind of disorder. I wish I can tell you more about it or that I would understand more about it, but I am just grateful for the work that has been done so that we can understand more and therefore have more to offer to these patients and their families and their communities that are support. Dr Nevel: Yeah, absolutely. That's always the key, and just really exciting that we're starting to understand this better so that we can hopefully treat it better and inform our patients better---and ourselves. Can you talk to us a little bit about the multidisciplinary team approach and taking care of patients with nonepileptic seizures? Who's involved, what does best practice model look like? You have a clinic there, obviously; if you could share with us how your clinic runs in the multidisciplinary approach for care of these patients? Dr Bermeo-Ovalle: The usual experience of patients dealing with functional seizures, because this is a condition that has neurological symptoms and psychiatric symptoms, is that they go to the neurologist and the neurologist does not feel sufficiently able to manage all the psychiatric comorbidities of the condition. So, the patient is sent to psychiatry. The psychiatry really finds themselves very hopeless into handling seizures, which is definitely not their area of expertise, and these patients then being- “ping-ponging” from one to the other, or they are eventually sent to psychotherapy and the psychotherapist doesn't know what they're dealing with. So, we have found with- and we didn't come up with this. We had wonderful support from other institutions who have done- been doing this for a longer time. That bringing all of this specialty together and kind of situating ourselves around the patient so that we can communicate our questions and our discrepancies and our decision between who takes care of what without putting that burden on the patient is the best treatment not only for the patient, who finally feels welcome and not burden, but actually for the team. So that the psychiatrist and the neurologist support the psychotherapist who does the psychotherapy, rehabilitation, mind the program. And we also have the support and the involvement of neuropsychology. So, we have a psychiatrist, a neurologist, social worker, psychotherapist and neuropsychology colleagues. And together we look at the patient from everywhere and we support each other in the treatment of the patient, keeping the patient in the middle and the interest of the patient in the middle. And we have found that that approach has helped our patients the best, but more importantly, makes our job sustainable so that none of us is overburdened with one aspect of the care of the patient and we feel supported from the instances that is not our most comfortable area. So that is one model to do it. There's other models how to do it, but definitely the interdisciplinary care is the way to go so far for the care of patients with functional neurologic symptom disorders and with functional seizures or nonepileptic seizures in particular. Dr Nevel: Yeah, I can see that, that everybody brings their unique expertise and then doesn't feel like they're practicing outside their, like you said, comfort zone or scope of practice. In these clinics---or maybe this happens before the patient gets to this multidisciplinary team---when you've established a diagnosis of nonepileptic seizures, what's your personal approach or style in terms of how you communicate that with the patient and their loved ones? Dr Bermeo-Ovalle: It is important to bring this diagnosis in a positive term. You know, unfortunately the terminology question is still out and there's a lot of teams very invested into how to better characterize this condition and how to- being told that you don't have something is maybe not that satisfying for patients. So, we are still working on that, but we do deliver the diagnosis in positive terms. Like, this is what you have. It's a common condition. It’s shared by this many other people in the world. It's a neuropsychiatric disorder and that's why we need the joint or collaborative care from neurology and psychiatry. We know the risk factors and these are the risk factors. You don't have to have all of them in order to have this condition. These are the reasons why we think this is the condition you have. There is coexisting epilepsy and functional seizures as well. We will explore that possibility and if we get to that conclusion, we will treat these two conditions independently and we- our team is able to treat both of them. And we give them the numbers of our own clinic and other similar clinics. And with that we hope that they will be able to get the seizures under better control and back to whatever is important to them. I tell my trainees and my patients that my goals of care for patients with functional seizures are the same as my patients with epileptic seizures, meaning less seizures, less disability, less medications, less side effects, less burden of the disease. And when we communicate it in that way, patients are very, very open and receptive. Dr Nevel: Right. What do you think is a mistake to avoid? I don't know if “mistake” is necessarily the right word, but what's something that we should avoid when evaluating or managing patients with nonepileptic seizures? What’s something that you see sometimes, maybe, that you think, we should do that differently? Dr Bermeo-Ovalle: I think the opportunity of engaging with these patients is probably the hardest one. Because neurologists have the credibility, they have the relationship, they have- even if they don't have a multi-disciplinary team all sitting in one room, they probably have some of the pieces of this puzzle that they can bring together by collaborating. So, I think that missing the opportunity, telling the patient, this is not what I do or this is not something that belongs to me, you need to go to a mental health provider only, I think is the hardest one and the most disheartening for patients because our patients come to us just like all patients, with hopes and with some information to share with us so that we can help them make sense of it and have a better way forward. We as neurologists know very well that we don't have an answer to all our patients, and we don't offer zero seizures to any of our patients, right? We offer our collaborative work to understand what is going on and a commitment to walk in the right direction so that we are better every day. And I do think wholeheartedly that that is something that we can offer to patients with functional seizures almost in any environment. Dr Nevel: Yeah, absolutely. And using that multidisciplinary approach and being there with your patient, moving forward in a longitudinal fashion, I can see how that's so important. What do you find most challenging and what do you find most rewarding about caring for patients with nonepileptic seizures? Dr Bermeo-Ovalle: The thing that I find more challenging are the systemic barriers that the system still places. We discuss with the patients, what is the right time to go to the emergency room or not? Because the emergency room may be a triggering environment for patients with functional seizures and it may be a place where not everybody is necessarily attuned to have this conversation. Having said that, I never tell any of my patients not to go to the emergency room because I don't know what's happening with them. As a matter of fact, we're getting a lot of information on high mortality rates in patients with functional seizures, and it’s not because of suicide and is probably not related to the seizure. Maybe this is---you know, this is speculation on my part---that is because they get to more severe conditions in other things that are not the functional seizures because they just experienced the healthcare system as very hostile because we are very in many instances. So, navigating that is a little bit difficult, and I try to tell them to have the doctors call me so that I can frame it in a different way and still be there for them. But I can tell you this clinic is the most rewarding clinic of all my clinical activities. And I love with all my heart being an epileptologist and seeing my patients with epilepsy. But the number of times my patients with functional seizures say, nobody had ever explained this to me, nobody had ever validated my experience in front of my family so that I'm not- like, feel guilty myself for having this episode, I can't tell you how many times. And obviously patients who come to the nonepileptic seizure clinic already know that they come to the nonepileptic seizure clinic, so that- you can say it's a selection of patients that are already educated in this condition to come to the clinic. But I would love everybody to know managing this population can be enormously, enormously satisfying and rewarding. Dr Nevel: Especially for, I imagine, patients who have been in and out of the ER, in and out of the hospital, or seen multiple providers and make their way to you. And you're able to explain it in a way that makes sense and hopefully reduces some of that stigma maybe that they have been feeling. Dr Bermeo-Ovalle: And along with that, iatrogenic interventions, unnecessary intubations, unnecessary ICUs; like, so much. And I think, I... /episode/index/show/continuumjournal/id/34884310

Surgical Treatments, Devices, and Nonmedical Management of Epilepsy With Dr. Daniel Friedman 03/12/2025

Surgical Treatments, Devices, and Nonmedical Management of Epilepsy With Dr. Daniel Friedman Many patients with epilepsy are unable to acheive optimal seizure control with medical therapy. Palliative surgical procedures, neurostimulation devices, and other nonpharmalogical treatments can lead to a meaningful reduction in seizures and improved outcomes. In this episode, Teshamae Monteith, MD FAAN, speaks with Daniel Friedman, MD, MSc, author of the article “Surgical Treatments, Devices, and Nonmedical Management of Epilepsy,” in the Continuum® February 2025 Epilepsy issue. Dr. Montieth is a Continuum® Audio interviewer and an associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida. Dr. Friedman is a professor (clinical) of neurology at NYU Grossman School of Medicine and Director of NYU Langone Comprehensive Epilepsy Center at NYU Langone Health in New York, New York. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum Journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Monteith: This is Dr Teshamae Monteith. Today, I'm interviewing Dr Daniel Friedman about his article on surgical treatments, devices, tools, and non-medication management of epilepsy, which appears in the February 2025 Continuum issue on epilepsy. Welcome to the podcast. How are you? Dr Friedman: I'm well, how are you? Dr Monteith: Thank you for your article. Dr Friedman: Thank you for the opportunity to talk today. Dr Monteith: Why don't you introduce yourself? Dr Friedman: So yeah, so I'm Dan Friedman. I am a professor of neurology here at NYU Grossman School of Medicine and I am the director of the NYU Comprehensive Epilepsy Center. I'm primarily an adult neurologist and I treat teens and adults with hard- difficult-to-treat epilepsy, including surgical treatments for epilepsy. Dr Monteith: And I know you see a lot of patients because I did my residency there. And so, when you graduate, you get a lot of it, like I think many, many residents. What inspired you to choose epilepsy as a profession? Dr Friedman: I came to neurology through my interest in neuroscience. I was a neuroscience undergraduate. I was very interested in the brain and brain function. Particularly, I was interested in how neurons communicate and organize to entrain and rhythms and that encode information. And through that interest and through my experiences in the laboratory, I actually became interested in how they do that in pathological circumstances like seizures. And so, I started reading about epilepsy, and then when I started seeing patients with epilepsy, you know, I decided this is the specialty for me for a lot of reasons. One is it combines inpatient and outpatient care. You get to establish long-term relationships with patients. For many of my patients, I'm probably the doctor that they see most often. You see people across the lifespan. And what I'm going to talk about today is for some people, you actually get to cure their disease, which at the time I was coming into neurology was something pretty rare. Dr Monteith: Yeah, that's great. Why don't you tell us, what were you thinking when you started writing the article? What did you set out to do? Dr Friedman: What I really wanted to do is to educate neurologists out there about the options that they have for their patients with epilepsy, especially those with difficult-to-treat or drug-resistant epilepsy, and give them the tools to communicate those options. Especially for them to understand the rationale, why we choose the interventions that we do as epileptologists, how to appropriately refer patients and have them be partners in that discussion with patients and families. One of the things that we have known for a long time is that the time to referral for things like epilepsy surgery is too long. You know, the average patient with drug resistant epilepsy who undergoes epilepsy surgery waits about twenty years. And for patients who could have curative therapy, you know, become seizure free, that's a lot of life years lost. If we can get patients to that potentially life-altering therapy earlier, that'd be great. Dr Monteith: Yeah, that is really impactful as you think about it. So why don't you tell us what the essential points of your article? Dr Friedman: The central point of my article is really that when patients have drug-resistant epilepsy, which means that our available anti-seizure medicines are not controlling their seizures to the degree that they need, there are other treatment options. Some of those are what we call curative, which means that they could stop their seizures entirely; and some of them are palliative, they could reduce the frequency or severity of seizures and improve quality of life and other outcomes. The other thing that I wanted to highlight was, in addition to these types of therapies, there are other tools we have at our disposal that can improve the quality of life and safety of our patients with epilepsy, including devices for seizure monitoring. Dr Monteith: And how do you define drug-resistant epilepsy? I feel like that could be a moving target. Dr Friedman: The International League Against Epilepsy actually set out to define it about a decade ago, and they defined it as patients who fail at least two appropriately selected anti-seizure medicines due to lack of efficacy. Then they're still having ongoing seizures. What does that mean? So, that means that the medicine that was chosen was appropriate for the type of seizures that they have, whether it's focal or generalized, and that it didn't work because of a lack of efficacy and not because of side effects. And we know from multiple studies that once patients fail two medications, the likelihood that the third, fourth, fifth, etcetera, medicine will control their seizures becomes smaller and smaller. It's not impossible, but the rates fall below five percent. And so we call those patients drug-resistant. Dr Monteith: So, it sounds like despite newer therapies, really things haven't changed in ten years. Dr Friedman: Yeah, unfortunately, at least when the concept was first investigated back in 2000 by Quan and Brody, they found that a third of patients were drug-resistant. When they went back in the mid-2010s to relook at these patients, despite the introduction of many new medications, the rate of patients who were drug-resistant was essentially unchanged. There may be therapies that are emerging or in development that may have better odds, but right now we don't really understand what makes people drug resistant and how we can target that. Dr Monteith: But you do raise a good point that this is about efficacy and not tolerability. And at least for some of the newer medications, they're better tolerated. If you stop the medicine because you had some side effect, that might change how that person has classified better-tolerated treatments. Dr Friedman: It's true. And better-tolerated treatments, you can potentially use higher doses. One of the things that is not in the definition of drug-resistant epilepsy, but as a practicing neurologist, we all know, is that the patients have to take the medicine for it to be effective. And unfortunately, they have to take it every day. And if the medicine makes them feel bad, they may choose not to take it, present to you as drug-resistant, when in reality they may be drug-sensitive if you got them on medicine that doesn't make them feel bad. Dr Monteith: So why don't we talk about patients that are ideal candidates for epilepsy surgery? Dr Friedman: The ideal candidates for epilepsy surgery… and I'll start by talking about curative epilepsy surgery, where the goal of the surgery is to make patients seizure-free. The best candidates are patients who have lesional epilepsy, meaning that there is a visible MRI abnormality like a focal cortical dysplasia, hippocampus sclerosis, cavernoma in a part of the brain that is safe to resect, non-eloquent, and where you can safely perform a wide margin of resection around that lesion. It helps if they have few or no generalized tonic-clonic seizures and a shorter duration of epilepsy. So the ideal patient, the patient that if they came to my office, I would say you should get surgery right now, are patients with non-dominant temporal lobe epilepsy of a few years’ duration. So as soon as they've shown that they're not responding to two medicines, those are the ideal patients to say, you would have the most benefit and the least risk from epilepsy surgery. We know from studies that patients with temporal lobe epilepsy do a little better with surgery. We know patients who have a visible lesion on MRI do better with epilepsy surgery. We know that patients who have infrequent secondarily generalized seizures do better. But all patients with drug-resistant epilepsy should be considered for some form of surgery because even if they're not candidates for a curative surgery, there may be some palliative options, whether it's surgical resections that lessen the severity of their seizures or neurostimulation devices that reduce the frequency and severity of seizures. Ideal candidates, the ones that you would push through sooner rather than later, are those who have the likelihood of the best outcomes and the least risk of neurocognitive decline. Dr Monteith: So, you mentioned that there may be other candidates that still benefit, although maybe not ideal. You mentioned neuromodulation. What other interventions are available? Dr Friedman: For patients who are not candidates for resective surgery, there are several neurostimulation options. There's vagus nerve stimulation, which has been around the longest. It is a device that is implanted in- under the skin near the clavicle and has a lead that goes to the left vagus nerve and delivers stimulation, electrical stimulation to the nerve. For reasons we don't fully understand, it can reduce the both the frequency and severity of seizures. Seldom does it make people seizure free, but the reduction in seizure frequency for many patients is associated with improved quality of life, reduced risk of injury, and even reduced rates of SUDEP. We also have two intracranial neurostimulation devices we use for epilepsy. One is the responsive neurostimulator. So, this is a device that- it has leads that are implanted directly into the seizure focus and sense electrocortical brain activity and deliver electrical stimulation to attempt to abort abnormal brain activity. So functioning kind of like a cardiac defibrillator for the heart, but for seizures in the brain. And because these devices have two leads, they can be used to treat people with more than one seizure focus---so up to two---or be used in patients who are not candidates for resection because their seizure focus is in language cortex, motor cortex, things that would be unable to resect. And the RNS has somewhat better efficacy in terms of percent reduction in seizures compared to the VNS, but obviously because it's an intracranial device, it's also a little riskier. It has more potential for neurosurgical adverse effects. There's also a deep brain stimulator for epilepsies, the same exact device that we use to treat movement disorders. We can implant in the thalamus, in either the anterior nucleus of the thalamus or now, for some patients, into the central median nucleus of the thalamus, and deliver open loop stimulation to treat epilepsy and reduce the frequency and severity of seizures as well. Unlike the RNS, you don't have to localize the seizure focus, so you don't need to know exactly where the seizures are coming from. And you could treat patients with multifocal epilepsy with seizures coming from more than two locations or even generalized seizures. Dr Monteith: So, it sounds like there are a lot of options available to patients. I think one of the things I find challenging is when we have patients that may have some cognitive dysfunction, especially in the hospital, and they've had some seizures that are very obvious, but then there are these, maybe, events that you wonder are seizures. So, what is the utility of some of these seizure detection devices? Dr Friedman: The development of seizure detection devices started out primarily with the observation that a majority of cases of sudden unexpected death and epilepsy, or SUDEP, occurred following tonic-clonic seizures. And there was a need to be able to monitor for convulsive seizures, especially that occur at night when people were otherwise unattended. And so, the first generation of devices that were developed came on the market, essentially detected convulsive seizures, and they alerted caregivers nearby who are able to come to the bedside, provide basic seizure first aid, turn people on the side. And theoretically all this---this hasn't been shown in studies---prevents SUDEP. And so, the ones that are currently available on the market are focused on the detection of convulsive seizures, mostly generalized tonic-clonic seizures, but some devices can also detect other seizures with very prominent motor components. What we don't have yet available to us, and what people are working on, are devices that detect nonconvulsive seizures. We know that patients who have focal impaired aware seizures are often amnestic for their seizures. They don't know they had a seizure if family members aren't there to observe them. They may never report them, which makes treating these patients very difficult. How do you quantify disease burden in your headache patients, for instance? You say, how many headache days did you have since we last met in the clinic? Your patients will be able to report on their calendar, this many days. Well, imagine if the patients had no awareness of whether or not they had a headache day. You wouldn't know if your therapy is working or not. In epilepsy, we need those types of devices which can tell us whether patients are having seizures they're unaware of, and that may be more subtle than convulsions. Dr Monteith: Oh, that'd be great for headache, too. You just gave me an idea, but that's the next podcast. So, you mentioned SUDEP, really important. How good are surgical interventions at reducing what we would think the prevalence of SUDEP? Dr Friedman: For me that is one of the primary motivations for epilepsy surgery in patients who are drug-resistant, because we know that if patients who are candidates for epilepsy surgery have high SUDEP rates. Estimates range from six to nine per thousand patients per year. If surgery is successful, their mortality rates go down to the general population level. It literally can be lifesaving for some patients, especially when you're talking about curative epilepsy surgery. But we also know that the biggest driver for SUDEP risk is tonic-clonic seizures and the frequency of those tonic-clonic seizures. So even our palliative interventions, which can reduce the frequency and severity of seizures, may also reduce the risk of SUDEP. So, we know in study- observational studies of patients with VNS and with RNS, for instance, the rates of SUDEP in patients treated with those devices are lower than expected for the drug-resistant epilepsy population. Dr Monteith: Let's talk a little bit about some of these prediction models. And you have a lot of great work in your article, so I don't want to get into all the details, but how do you use that in the real world? Do you communicate that with patients? How do you approach these prediction factors? Dr Friedman: There are two places where, I think, clinical prediction tools for epilepsy surgery have a role. One is, for me, in my clinic where I'm talking to patients about the risks and benefits for surgery, right? You want to be able to accurately communicate the likelihood that the surgery is going to give you the desired outcome. So patients and their families can make educated decisions, be weighing the risks and benefits. I think it's important to be realistic with patients because surgery, like- you know, any surgery is not without risk, both acute risks and long-term risks. You're removing part of the brain, and, you know, every part of the brain is important. That's where I use prediction tools. But I think it's also important for the general neurologist, especially trying to triage which patients you are going to be aggressive with referring to a comprehensive epilepsy center for evaluation. Where you may use your limited time and capital with patients to counsel them on surgical treatments. Where a healthcare system with limited resources prioritizes patients. So, there's a significant need for having prediction tools that only take the input that a general neurologist seeing a patient in the clinic would have at hand. You know, the history, an MRI, an interictal EEG. Dr Monteith: I guess part of that prediction model includes adverse outcomes that you're communicating as well. Dr Friedman: Certainly, for me, when I'm discussing surgery for the patient in front of me, I will use prediction models for adverse outcomes as well that are informed by the kind of surgery we're proposing to do, especially when talking about things like language dysfunction and memory dysfunction after surgery. Dr Monteith: So, you mentioned a lot of great advances, and certainly since I was a resident, which wasn't that long ago. Why don't you tell me how some of these interventions have changed your clinical practice? Dr Friedman: Thinking about epilepsy surgery, like other surgical specialties, there's been a move to more minimally invasive approaches. For instance, when I started as an epilepsy fellow fifteen years ago, sixteen years ago, most of our surgeries involve removing a large portion of the skull, putting electrodes on the brain, doing resections through big craniotomies which were uncomfortable and risky, things like that. We now do our phase two or intracranial EEG monitoring through small burr holes in the brain using robotically placed electrodes. For many of our patients, we can actually treat their epileptic focus with a laser that is targeted through a small catheter and MRI guidance. And patients are usually home in two days with, you know, a lot less discomfort. Dr Monteith: Well, that's great. I didn't expect that one, but I do think that translates to many areas of neurology. Really just this idea of meeting their goals and personalizing their care. My last question is, what out of these advances and what you know about the future of epilepsy, what makes you the most excited and what gives you the most hope? Dr Friedman: I think there are a lot of exciting things in epilepsy. Last count I heard, there's something like over a hundred biotech companies developing epilepsy therapies. So that gives me hope that people are still interested in meeting the unmet needs of patients with epilepsy. And some of these therapies are really novel. For instance, there's a trial of stem cell treatments for drug-resistant temporal lobe epilepsy that's ongoing now, where inhibitory interneuron progenitor cells are implanted in the brain and kind of restore the brain circuit disruptions... /episode/index/show/continuumjournal/id/34884280

First Seizures, Acute Repetitive Seizures, and Status Epilepticus With Dr. David Vossler 03/05/2025

First Seizures, Acute Repetitive Seizures, and Status Epilepticus With Dr. David Vossler Emergency treatment may be necessary after a person's first seizure or at the onset of abnormal acute repetitive (cluster) seizures; it is required for status epilepticus. Treatment for these emergencies is dictated by myriad clinical factors and informed by published guidance as well as emerging research. In this episode, Lyell K. Jones, MD, FAAN, speaks with David G. Vossler, MD, FAAN, FACNS, FAES, author of the article “First Seizures, Acute Repetitive Seizures, and Status Epilepticus,” in the Continuum® February 2025 Epilepsy issue. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Vossler a clinical professor of neurology at the University of Washington School of Medicine in Seattle, Washington. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today, I'm interviewing Dr Dave Vossler, who has recently authored an article on emergent seizure management, taking care of patients with the first seizure, acute repetitive seizures, and status epilepticus, which is an article in our latest issue of Continuum covering all topics related to epilepsy. Dr Vossler is a neurologist at the University of Washington, where he's a clinical professor of neurology and has an active clinical and research practice in epileptology. Dr Vossler, welcome. Thank you for joining us today. Why don't you introduce yourself to our listeners? Dr Vossler: Thank you very much for the introduction, Lyell. It's a pleasure to speak with you on this podcast, and I hope to go over a lot of important new information in the management of seizure emergencies. As you said, I'm a clinical professor in neurology at University of Washington, been in medicine for many decades now and have published and done research in this area. So, I'm anxious to give you not only my academic experience, but also talk about my own management of patients with status epilepticus over the last four decades. Dr Jones: Yeah, that's fantastic. And I always appreciate hearing from experienced clinicians, and I think our readers and our listeners do appreciate that voice of clinical expertise. And I'll tell you this is a topic, you know, as a neurologist who doesn't see many patients with acute seizure emergencies in my own practice, I think this is a topic that gives many clinicians, including neurologists, some anxiety. Your article, Dr Vossler, is really chock-full of helpful and clinically relevant considerations in the acute management of seizures. So, you now have the full attention of a huge audience of mostly neurologists. What's the one most important practice change that you would like to see in the care of patients with either first or acute prolonged seizures? Dr Vossler: Without a doubt, the most important clinical takeaway with regard to the status epilepticus---and for status epilepticus, many, many clinical trials, research trials have been done over the last couple decades and they all consistently show the same thing, that by and large most patients who have status epilepticus are underdosed and undertreated and treated too slowly in the initial stages of the status epilepticus. And it's important to use full bolus dosages of benzodiazepines to prevent mortality, morbidity, and later disability of these patients. To prevent the respiratory depression, many physicians are afraid to use higher doses of benzodiazepines, even guideline-recommended doses of benzodiazepines for fear of respiratory depression. But it's actually counterintuitive. It turns out that most cases of respiratory depression are due to inadequate doses and due to the status epilepticus itself. We know there's greater mortality, we know there's greater morbidity and we know that there's greater need for higher dose, subsequent, anti-seizure medications, prolonged status, if we don't use the proper doses. So, we'll kind of go over that a little bit, but that is the one clinical takeaway that I really would like our listeners to have. Dr Jones: Let's follow that thread a little bit. Dave, I know obviously we will speak in hypotheticals here. We're not going to talk about actual patients, but I think we've all been in the clinical situation where you have a patient who comes into the emergency room usually who's actively seizing, unknown history, don't know much about the patient, don't know much about the circumstances of the onset of the seizure. But we now have a patient with prolonged convulsive seizures. How do we walk through that? What are the first steps in the management of that patient? Dr Vossler: Yeah, well, I'll try to be brief for the purposes of the podcast. We do, of course, go through all of that in detail in the Continuum article, which hopefully everybody will look at very carefully. Really in the first table, the very first table of the article, I go through the recommended guideline for the American Epilepsy Society on the management of what we call established status epilepticus. The scenario you're talking about is just exactly that: established status epilepticus. It's not sort of evolving or developing status. We're okay they're having a few seizures and we're kind of getting there. No, this patient is now having evidence of convulsive seizure activity and it's continuing or it's repeated seizures without recovery. And so, the first phase is definitely a benzodiazepine and then the second phase is then a longer-acting bolus of a drug like phosphenotoine, valproic acid or levetiracetam. I could get into the details about dosing of the benzodiazepines, but maybe I'll let you guide me on whether we wanted to get into that kind of detail right at the outset. It's going to be a little bit different. For children, its weight-based dosing, but for adults, whether you use lorazepam or you use diazepam or you use midazolam, the doses are a little bit different. But they are standardized, and gets back to this point that I made earlier, we're acting too slow. We're not getting these patients quick enough, for various reasons, and the doses that are most commonly used are below what the guidelines call for. Dr Jones: That's great to know, and I think it's fine for the details to refer our listeners to the article because there are great details in there about a step-by-step approach to the established status epilepticus. The nomenclature and the definitions have evolved, haven't they, Dr Vossler, over time? Refractory status epilepticus, new-onset refractory status epilepticus, super refractory status epilepticus. Tell us about those entities, how they're distinguished and how you approach those. Dr Vossler: That's an important thing to kind of go over. They- in 2015, the International League Against Epilepsy, ILAE, which is, again, our international organization that guides our understanding of all kinds of things epileptic in nature around the world. In 2015 they put out a definition of status epilepticus, but it used to be that patients had thirty minutes of continuous seizure activity or repetitive obvious motor seizures with impairment of awareness and they don't recover impairment between these seizures. And that goes on for thirty minutes. That was the old definition of status epilepticus. Now, the operational definition is five minutes. And I think that's key to understand that, after five minutes of this kind of overt seizure activity, you need to intervene. And that's what's called T1 in the 2015 guideline, the international guideline. There are a bunch of different axes in the classification of status that talk about semiology, etiology, EEG patterns, and what age group you're talking about. We won't really get into those in the Continuum article because that's really more detailed than a clinician really should be. Needing to think about the stages, what we call the stages of status epilepticus that you mentioned and I alluded to earlier are important. And that is sort of new nomenclature, and I think probably general neurologists and most emergency room physicians aren't familiar with those. So, it just briefly goes through those. Developing status epilepticus is where you're starting- the patient’s starting to have more frequent seizures, and it's heading essentially in the wrong direction, if you will. Established status epilepticus, as I mentioned, is, you know, this seizure act, convulsive or major, major outward overt seizure activity lasting five minutes or more, at which time therapy needs to begin. Again, getting back to my point, what doesn't happen often enough is we're not- we're intervening too late. Third is refractory status epilepticus, which refers to status epilepticus which continues despite adequate doses of an initial benzodiazepine given parenterally followed by a full loading dose of a single non-sedating anti-seizure medicine, which today includes phosphenotoine IV valproic acid or IV levetiracetam. In the United States, and increasingly around the world, people really are using levetiracetam. First, it has some advantages. There's now proof from a class one NIH-funded trial. We know that these three drugs are equivalent at the full doses that I go over in the article. You have your kind of dealer's choice on those. Phenobarbital, which we used to use and I used as a resident as long as forty years ago, is really a second choice drug because of its sedating and other side effects. But around the world in resource-poor countries phenobarbital can be used and, in a pinch, certainly is an appropriate drug. And then finally, you mentioned super refractory status epilepticus and that's status that's persisting for more than twenty four hours. Now, despite initial benzo and non-sedating anti-seizure medicine, but also lasting more than twenty four hours while receiving an intravenous infusional sedating, anesthetizing anti-seizure medicine like ketamine, propofol, pentobarbital or midazolam drips. Dr Jones: So, it sounds like the definitions have evolved in a way that improves the outcomes, right? To do earlier identification of status epilepticus and more aggressive management, I think that's a great takeaway. If we move all the way to the other end of the spectrum, let's move to the ambulatory setting and we have a patient who comes in and they've had one seizure, they're an adult; one seizure, the first seizure. The key question is, how do we anticipate the risk of future seizures? But walk us through how you talk to that patient, how you evaluate that patient to decide if and when to start anti-seizure medicines. Dr Vossler: Well, it depends a little bit if it's an adult or a child, but the decision making process and the data behind it is pretty robust now. And the decision making process is pretty similar for adults and children, with some differences which I can talk about. First of all, first seizures. I think it's really important to stress that there's been so much research in this area. I'd like to get a cross point that they're not as innocuous as I think many general neurologists might suspect. We know that there is a two- to threefold increased risk of death in children and adults following a first seizure. Moreover, the risk of a second seizure, both in kids and adults, is about 36% two years after that first seizure. It's about 46% five years after that first seizure. It's really pretty substantial. The risk of a second seizure is increased twofold. It doubled in the presence of any kind of a history of prior brain insults that could result in seizures. Could be infections, it could be a prior stroke, it could be prior significant brain trauma. It's also doubled in the presence of an EEG, which shows epileptiform discharges like spikes and sharp waves---and not just a sort of borderline things like sharply contoured rhythmic Theta activity. That's really not what we're talking about. We're talking about overt epileptiform discharges. It's doubled in the presence of lesion that can be seen on imaging studies, and it's doubled in the presence of seizures if that first seizure occurs during sleep. So, we have a number of things that double the risks, above the risk of a second seizure, above that 36% at two years and 46% at five years that I spoke about. And so those things need to be considered when you're counseling a patient about that. Should you be on an anti-seizure medicine after that first seizure? Specifically, to the point of anti-seizure medications, the guideline that was done, the 2015 guideline that was done by the American Academy of Neurology for adults, and the 2003 guideline was actually a practice parameter that was done by the Academy and the American Epilepsy Society for children, are really kind of out of date. They talk about the adverse effects of anti-seizure medications, but when you look back at the studies that were included in developing that practice parameter for kids and guidelines for adults, they are the old drugs: carbamazepine, phenytoin, phenobarbital and valproate. Well, I don't think I need to tell this audience, this well-educated audience, that we don't use those drugs anymore. We are using more modern anti-seizure medicines that have been developed since 1995; things like lamotrigine, levetiracetam, and lecosamide. Those three in particular have very low adverse events. So, the guideline that the Academy, American Academy Neurology and American Epilepsy Society put together for kids and for adults talks about this high adverse event profile. And so, you need to take a look at the risks that I talked about of a seizure recurrence and balance that against adverse effects. But I'm here to tell you that the newer anti-seizure medicines---and by newer I'm talking in the last thirty years since lamotrigine was approved in 1995---these drugs have much better side effect profiles. And I think all epileptologists would agree with that. They're not necessarily more effective, but they are better tolerated. That makes the discussion of the risk of a second seizure, the risk of mortality versus side effects of drugs, it really pushes the risk category higher on the first side and not on the side of drugs. We know that if you take an anti-seizure medicine, you reduce your risk of a second seizure by half. Now, that's not sustained over five years, but over the first two years, you've reduced it by half. In a person who's driving, needs to get to work, has to take the kids to school, whatever, most of my patients are like, yeah, okay, sign me up. These drugs are really pretty well tolerated. There's a substantial risk of a second seizure. So, I'll do that. In a kid, a child that's, you know, not driving yet, that might be a different discussion. And the parents might say, well, I'd rather not have my son exposed, my daughter exposed to this. They're trying to go to school. They're trying to learn. We don't want to hinder that. We'll wait for a second seizure and then if they have a second seizure, which by the way is, you know, one of the definitions of epilepsy, well then they have epilepsy, then they probably will need to go on the seizure medication. Dr Jones: Great summary, Dr Vossler, and it is worth our audience being aware that the evidence has evolved alongside the improvement in the adverse effect profile. And sounds like your threshold is a little lower to treat then maybe it would have been some time ago, right? Dr Vossler: I would say that's exactly correct in my opinion. Particularly for adults, absolutely. Dr Jones: That's fantastic, Dr Vossler. I imagine there are a lot of aspects of caring for these patients that are challenging, and I imagine many scenarios are actually pretty rewarding. What do you find the most rewarding aspect of caring for patients with acute seizure management? Dr Vossler: Yes, I mean, that is really true. I would say that the most challenging things are treating refractory status epilepticus, but worse yet, new onset refractory status epilepticus and the super refractory status epilepticus, which I talk extensively about or write extensively about in the article and provide a lot of guidance on. Really, those conditions are so challenging because they can go on for such a long time. Patients are hospitalized for a long time. A lot of really good clinical guidance doesn't exist yet. There is a tremendous amount of research in that area which I find exciting, and really there's an amazing amount of international research on that, I think most of our audience probably is unaware of. And certainly, with those conditions, there is a high risk of later disability and mortality. We go through all of that in the article. The rewards really come from helping these people. When someone was super refractory status and it were non- sorry, new onset refractory status epilepticus, has been in the hospital for thirty days, it gets really hard for everybody; the family, the patient. And for us, it wears on us. Yet when they walk out the door, and I've had these people come back to the epilepsy clinic and see me later. We're managing their anti-seizure medications. They've survived. The NORSE patients often have substantial disability. They have cognitive and memory and even some psychiatric disability. But yet we can help them. It's not just management in the hospital, but it's getting to know these people, and I take them from the hospital and see them in my clinic and manage them long-term. I get a lot of great satisfaction out of that. We're hoping to do even better, stop patients’ status early and get them to recover with no sequelae. Dr Jones: What a great visual, seeing those patients who have a devastating problem and they come back to clinic and you get the full circle. And what a great place to end. Dr Vossler, thank you so much for joining us, and thank you for such a thorough and fascinating discussion on the importance of understanding and managing patients with the first seizure, acute repetitive seizures, and status epilepticus. Dr Vossler: Thank you very much, Lyell. Dr Jones: Again, we've been speaking with Dr Dave Vossler, author of an article on emergent seizure management, first seizures, acute repetitive seizures and status epilepticus in Continuum's most recent issue on epilepsy. Please check it out, and thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio. /episode/index/show/continuumjournal/id/34884250

Epilepsy Genetics With Dr. Sudha Kessler 02/26/2025

Epilepsy Genetics With Dr. Sudha Kessler Genetic testing plays a key role in the evaluation of epilepsy patients. With the expanding number of choices for genetic tests and the complexity of interpretation of results, genetic literacy and knowledge of the most common genetic epilepsies are important for high-quality clinical practice. In this episode, Gordon Smith, MD, FAAN speaks Sudha Kilaru Kessler, MD, MSCE, author of the article “Epilepsy Genetics,” in the Continuum February 2025 Epilepsy issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Kessler is an associate professor of neurology and pediatrics at Perelman School of Medicine at the University of Pennsylvania and Children’s Hospital of Philadelphia in Philadelphia, Pennsylvania. ADDITIONAL RESOURCES Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the Academy of Neurology: SOCIAL MEDIA Host: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Smith: Hello, this is Dr Gordon Smith. Today I've got the great pleasure of interviewing Dr Sudha Kessler about her article on epilepsy genetics, which appears in the February 2025 Continuum issue on epilepsy. Sudha, welcome to the podcast and please introduce yourself to our audience. Dr Kessler: Oh, thank you so much. I'm Sudha Kessler. I am a pediatric epileptologist here at the Children's Hospital of Philadelphia and the University of Pennsylvania. Dr Smith: Tell us a little bit about yourself. Are you a geneticist too, or how did you get into this particular topic? Dr Kessler: Yes, I want to emphatically say that I am not a geneticist. I'm not an expert in epilepsy genetics at all. I take care of all sorts of patients with epilepsy. I actually do mostly epilepsy surgery-related care. But this part of epilepsy is, every year, increasingly important to our everyday practice. And I think it's fascinating, often a little daunting. I think I was asked to get involved with this article as a non-expert to help translate from the experts to the rest of us. Dr Smith: We're going to get there, because one of the things you do a really good job of in the article is talking about genetic concepts that are germane to everything we do. And I think you're an expert. You do it in a way that I understood. So, I'd like to get there, but- and this is a really hot area. For instance, I really loved your figure that shows the arc of discovery of genetic causes for epilepsy. It's really breathtaking, something we wouldn't have thought possible that long ago. And it's also a lot to digest. And so, I wonder if maybe we can begin by thinking about a framework and, for instance, you talk about these different groups of disorders. And one that seems to be particularly impacted by this unbelievable A-rated discovery. Our developmental and epileptic encephalopathies, or DEEs. What can you tell our listeners about that group of disorders? Dr Kessler: Sure. I think that, you know, most of what we think about in epilepsy genetics now has to do with disorders that are attributable to changes in a single gene. Genetics is obviously much more complicated than that, but that's still where we are in the stage of discovery. And the graph in the article is definitely one to take a look at because it represents the explosion that we've had in our understanding of single gene disorders leading to epilepsy and related manifestations. The DEEs are a group of disorders where any individual disorder is fairly rare, but as a group they are not that rare, and very impactful because they often cause epilepsy at a very young age. And either as a consequence of seizures or as a consequence of the underlying pathophysiology of that gene change, they are typically associated with really significant developmental impairments for a child 's entire life. Dr Smith: My understanding is that there's therapeutic development going on in this space. So, the early recognition of these genetic testing offers the promise of very impactful treatment---like we now do for SMA, for instance---early in the disease course. Dr Kessler: I think that's right. That's one of the most exciting parts of this field is that so much, just around the corner, for drug development, therapy development in this area. And as you can imagine, with a lot of these disorders, earlier intervention is likely to be much more impactful than later intervention when a lot of the developmental consequences are sort of… you know, when the cat 's already out of the bag, so to speak. Dr Smith: Yeah. So, this is really transformational and something that everyone who takes care of kids with epilepsy needs to know about, it seems. So on the other extreme, I guess, there are the self-limited epilepsies. I didn't really know about this in terms of genetic discovery, but can you talk about those disorders? Dr Kessler: Yeah, sure. I mean, I think some of these are the classic childhood epilepsy syndromes that we think about like childhood absence epilepsy or what we used to call benign romantic epilepsy and now call self-limited epilepsy of childhood with centrotemporal spikes. It's a mouthful, shortened to SeLECTS. Those are the epilepsies that occur typically in previously healthy children, that affects them for a few years and often remits so that epilepsy is just age-limited and doesn't continue for life. They clearly have genetic influences because they tend to run in families, but the genetics of them is not generally single gene associated. And so, we haven't actually explained why most of those kids actually get epilepsy. I think that'll be sort of another interesting area of discovery that will help us even understand some really fundamental things about epilepsy, like, why does this syndrome start at this age and tend to resolve by adolescence? Dr Smith: And the other thing I found interesting is disorders that I might have thought going into it would have a defined genetic cause or some of the disorders that there are not. So JME, for instance, or childhood absence, which is a little counterintuitive. Dr Kessler: It's completely counterintuitive. We call them genetic generalized epilepsies, and we know that they run in families, but we still know so little. I would say of all of the disorders that are mentioned in this article, that is the group where I think we have explained the genetic underpinnings the least well. Dr Smith: Yeah. Isn't that interesting? It's… wasn't it Yogi Berra who said, it's hard to predict things, particularly the future? So… Dr Kessler: Yes. Dr Smith: Who would have thought? So, we’ve talked a lot about kids. What about adults? You know, what role does genetic testing play in adults who have unexplained epilepsy? Dr Kessler: Yeah, I think that that is also a really important emerging area of knowledge. I think many epileptologists may think of genetic epilepsy as being solely pediatric. There are definitely not how many of these disorders can manifest for the first time in adulthood. Not only that, many of our children with childhood onset epilepsy that is due to a genetic problem grow up to become adults and will then need adult epilepsy care. In order to take care of both of those groups, it's really important for all epileptologists, including those that take care of adults, to have some knowledge of the potential impact of genetic testing. And how do you even approach thinking about it? Dr Smith: The message I guess I'm getting is if our listeners take care of patients with epilepsy, no matter how old those patients are, they need to be familiar with this. And the other message I'm getting is, it sounds like there are a lot of patients who really need genetic testing. And this came through in one aspect of your article that I found really interesting, right? So, what are the recommendations on genetic testing? So, the National Society of Genetic Counselors, as I understand it, said everyone needs genetic testing, right? Which I mean, they're genetic counselors, so. Which is great. In the International League Against Epilepsy, they recommended a more targeted approach. So, what's your recommendation? Should we be testing anyone with unexplained epilepsy, or should we be focusing on particular populations? Dr Kessler: Well, I guess I think about it as a gradation. There are certain populations that really deserve genetic testing, where it is going to be absolutely critical. You know, it's very likely that it will be critical knowledge to their care. If you diagnose somebody with epilepsy and you do imaging and that imaging does not reveal an answer, meaning you don't see a tumor or you don't see an old stroke or some other sort of acquired lesion, the next pillar of testing for understanding underlying etiology is genetic testing. That is the point at which I typically send my patients, and that's whether they're refractory or not. I think in the past some people felt that only patients with refractory epilepsy deserve or require testing. I think the reason why not to limit it to that population is that what's on a person's mind with epilepsy, or a family's mind with epilepsy, is what's going to happen to my child or to me in the future? And if genetic testing can shed some light on that, that will have a huge impact on that person's life. Dr Smith: You've got great cases in your article, which, I just want to give you a compliment. The information and entertainment, frankly, for per page: off the charts. It's not a long article, packed with useful information. And, I mean, some of your cases are great examples of patients who are heading down the surgical epilepsy path and you discovered, nope, there's a genetic cause that really impacted their care. What's the yield, right? The number of patients that you send genetic testing on for epilepsy, what percentage come back positive for a relevant sequence variant that you think is either causing or contributing to their epilepsy? Dr Kessler: That's a great question. I think that is actually still in flux because it depends on the population of patients that are being sent for testing, obviously, and then also on what testing is being done. So, I know in at least one large recent meta-analysis, the overall yield was 17%. And somebody hearing that number might think, oh, that's not very high, but it's actually very comparable to the yield for imaging. And we all do MRIs and patients that have new-onset epilepsy where the yield of MRI testing is about 20% or so. So, quite comparable. And then with children with DEEs, the yield is much, much higher than that. Dr Smith: So, 17% is actually a really great diagnostic yield. When I think of my yield and doing genetic testing on patients who have an axonal CMT phenotype, right? I mean that's better than what I get. So, good for you. That's exciting. Dr Kessler: It's interesting. I think that maybe an assumption might be that you're working somebody up. You do a genetic test, it reveals a difference, and thus surgery is off the table. It's actually quite different than the head, which is that some results may make surgery be even more “on the table” because you might find a gene that is known to be associated with a propensity to vocal cortical dysplasia, for example. And you may take a good second look at that person's MRI imaging or do other imaging to reveal the MRI invisible vocal cortical dysplasia. Dr Smith: Outstanding point. Let's talk a little more about the genetic testing itself. So, we've got all these genes. We understand when to test. What do you do? For instance, last night I just looked at the company that we use for most of our neuromuscular testing and they have a genetic epilepsy next gen panel with, I don't know, three hundred and twenty genes, right? Do you use that kind of panel? Do you go directly to a whole EXO? What's the right approach? Dr Kessler: Yeah, I think that that is quite dynamic right now, meaning that recommendations seem to change often enough that I rely on help. I have the enormous good luck of working here at CHOP where there is a fantastic epilepsy genetics group that I can easily refer to, and I know not everyone has that resource. The current recommendation is to start with an exome if that is available and is covered by that patient's insurance. When exome is not available, then the next best thing is a gene panel. You know, in recent years there have been a lot of sponsored gene panels, meaning free to the patient, administered by a company that then, you know, has other uses for compiled or grouped genetic data. And I think that as long as all of that can be clearly explained to a patient, and- along with all of the other things so you have to explain to a patient before doing genetic testing, about the pluses and minuses of doing it, I think that you sort of go for the best test you can that's available to that patient. Dr Smith: The sponsored programs can be very, very helpful, particularly from a payer or a patient payment perspective. And so, I guess the lesson there is it's great if you got the resources and CHOP to help you decide, but better to get whatever panel you can get than to do nothing; or, of course, refer to a center if you're not comfortable. Dr Kessler: And also, just know that these things change often enough that if it's been a couple of years and you might want to recheck whether the EXO is available to that patient or whether a gene panel can be sent that includes more than they had eight years ago. Dr Smith: So, are there situations to go to the other extreme where you just do targeted sanger sequencing? Like, just sequence the specific gene of interest? Dr Kessler: Yeah, absolutely. I'm still a big proponent of thinking clinically about a patient. If there are clues in that patient's history, exam, imaging, anything that gives you some sense of the disorder that this patient might have. And I think a classic example would be tuberous sclerosis. If you see an infant who has new onset spasms, you see hypopigmented macules on their skin and their MRI shows a tuber, you know, also known as a focal cortical dysplasia, then sure, send the targeted sequencing for the TSC1 and TSC2 genes. Dr Smith: And Rett syndrome? Dr Kessler: And Rett syndrome would be another example. And there are many examples where, if you feel like you have a good sense of what the disorder is, I think it's completely acceptable to send the targeted testing. Dr Smith: So, I'm going to get further down the rabbit hole and get to from easier to harder. I always get confused about things like chromosomal microarrays or, like, karyotypes and rings and stuff like that. What role do these tests play and what do our listeners need to know about them? Dr Kessler: Yeah, I think that it is really important to have at least some knowledge of what each test can't tell you. I tell my medical students at my residence that all the time. With anything in medicine, you should know what you're asking of a test and what answers a test can tell you and can't tell you. It is baseline knowledge before requesting anything. And if you don't know, then it's best to ask. So, chromosomal microarray is used when you think that there is a large-scale derangement in a bunch of genes, meaning there is a whole section of a chromosome missing---that would be deletion, or that that information is duplicated or is turned around in a, you know, in a translocation. That is what- the kinds of things that that test can tell you. I think of doing a microarray when a child has not just epilepsy and intellectual disability, but also has, for example, other organ systems involved, because sections of chromosome can include many, many, many different genes and it can affect the body in larger ways. That's often when I think about that. So, a child with multiple congenital anomalies. Karyotype, which we think of as the most old-fashioned way of looking at our genes, still has some utility because it is useful for looking at a specific situation where the ends of arm of a chromosome get cut off and get sticky and then stick to each other and make a ring. For example, ring chromosome 20 is a disorder which can cause epilepsy, particularly hard-to-treat frontal lobe epilepsy, and that sometimes doesn't show up until adolescence or even early adulthood. That's just one example of something that karyotype can tell you. Dr Smith: And it goes without saying, but just to emphasize, these are things that you would miss completely on a next generation panel or a next genome? Dr Kessler: That's correct. Because this isn't about sequencing. This is about large structures. You know, with my patients, it's sometimes, I think, very hard to explain. It's hard enough to explain it to other physicians who aren't in genetics, but it's a whole other undertaking to explain it to families who may not have a lot of literacy about cell biology or genetics or, you know, anything related to that. So, I often rely on analogies. And one analogy I use is that if you're- all of your genetic information is like a book, that book is split into chapters and those are the chromosomes. And you can be missing entire paragraphs or have paragraphs duplicated. And that would be the kind of thing that we would be looking for with the chromosomal microarray with sequencing or, you know, with sequencing, we're looking for spelling of words, and we can look at one word at a time. That would be targeted sequencing. Or we can look at many, many words at a time. And that would be next gen sequencing. Dr Smith: I just want to say that you are the genetic whisperer. You know, translator. I love it. Dr Kessler: You can continue using it down to the level of explaining the possibility of a variant of unknown significance, which I think is sometimes difficult to explain. So, I often will say, I know how the word color is spelled: C O L O R. But sometimes in other places it will be spelled C O L O U R and that's still the same word, that's still color. That's just what we would call a population variant. If it is spelled C O M O R, that changes meaning; that is not a word, and that is probably a pathogenic variant. But if it gets misspelled and it’s K O L O R, then I'm not sure. Could that be a variant that means something different or not. And so that I would call that a variant of unknown significance, meaning its impact is to be determined. Dr Smith: So, I was going to ask you about variant calling, but you'd beat me to the punch. And that's a great metaphor that I will definitely remember. All right, here's another concept that I think people often find challenging, which is read depth. Can you tell us about reading depth or sequence depth? Dr Kessler: Yes, hopefully I can. Again, not an expert here, but as I understand it, the way next gen sequencing works is that pieces of DNA are getting read. And the number of times any given nucleotide is read in this process is the read depth. It basically just translates to the number of times the processor, the machinery of doing this,... /episode/index/show/continuumjournal/id/34884210

Neuroimaging in Epilepsy With Dr. Christopher Skidmore 02/19/2025

Neuroimaging in Epilepsy With Dr. Christopher Skidmore Neuroimaging is a tool to classify and ascertain the etiology of epilepsy in people with first or recurrent unprovoked seizures. In addition, imaging may help predict the response to treatment. To maximize diagnostic power, it is essential to order the correct imaging sequences. In this episode, Aaron Berkowitz, MD, PhD, FAAN speaks with Christopher T. Skidmore, MD, author of the article “Neuroimaging in Epilepsy,” in the Continuum February 2025 Epilepsy issue. Dr. Berkowitz is a Continuum® Audio interviewer and professor of clinical neurology at the University of California, San Francisco Dr. Skidmore is an associate professor of neurology and vice-chair for clinical affairs at Thomas Jefferson University, Department of Neurology in Philadelphia, Pennsylvania. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Berkowitz: This is Dr Aaron Berkowitz, and today I'm interviewing Dr Christopher Skidmore about his article on neuroimaging in epilepsy, which appears in the February 2025 Continuum issue on epilepsy. Welcome to the podcast, Dr Skidmore. Would you please introduce yourself to our audience? Dr Skidmore: Thank you for having me today. I'm happy to talk to you, Dr Berkowitz. My name is Christopher Skidmore. I'm an associate professor of neurology at Thomas Jefferson University in Philadelphia. I'm a member of the Jefferson Comprehensive Epilepsy Center and also serve as the vice chair of clinical affairs for the department. Dr Berkowitz: Thank you very much for joining us and for this fantastic article. It's very comprehensive, detailed, a very helpful review of the various types of brain pathology that can lead to epilepsy with very helpful images and descriptions of some of the more common findings like mesial temporal sclerosis and some of the less common ones such as cortical malformations, heterotopia, ganglioglioma, DNET. So, I encourage all of our listeners to read your article and take a close look at those images. So, hopefully you can recognize some of these findings on patients’ neuroimaging studies, or if you're studying for the right or the boards, you can recognize some of these less common congenital malformations that can present in childhood or adulthood with epilepsy. In our interview today, what I'd like to do is focus on some practical tips to approaching, ordering, and reviewing different neuroimaging studies in patients with epilepsy. So to start, what's your approach when you're reviewing an MRI for a patient with a first seizure or epilepsy? What sequence do you begin with and why, how do you proceed through the different sequences and planes? What exactly are you looking for? Dr Skidmore: It's an important question. And I think to even take a step back, I think it's really important, when we're ordering the MRI, we really need to be specific and make sure that we're mentioning the words seizures and epilepsy because many radiology centers and many medical centers have different imaging protocols for seizure and epilepsy patients as compared to, like, a stroke patient or a brain tumor patient. I think first off, we really need to make sure that's in the order, so that way the radiologist can properly protocol it. Once I get an image, though, I treat an MRI just like I would a CAT scan approach with any patient, which is to always approach it in the same fashion. So, top down, if I'm looking at an axial image. If I'm looking at a coronal image, I might start at the front of the head and go to the back of the head. And I think taking that very organized approach and looking at the whole brain in total first and looking across the flare image, a T2-weighted image and a T1-weighted image in those different planes, I think it's important to look for as many lesions as you can find. And then using your clinical history. I mean, that's the value of being a neurologist, is that we have the clinical history, we have the neurological exam, we have the history of the seizure semiology that can might tell us, hey, this might be a temporal lobe seizure or hey, I'm thinking about a frontal lobe abnormality. And then that's the advantage that we often have over the radiologist that we can then take that history, that exam, and apply it to the imaging study that we're looking at and then really focus in on those areas. But I think it's important, and as I've illustrated in a few of the cases in the chapter, is that don't just focus on that one spot. You really still need to look at the whole brain to see if there's any other abnormalities as well. Dr Berkowitz: Great, that's a very helpful approach. Lots of pearls there for how to look at the imaging in different planes with different sequences, comparing different structures to each other. Correspondent reminder, listeners, to look at your paper. That's certainly a case where a picture is worth a thousand words, isn't it, where we can describe these. But looking at some of the examples in your paper, I think, will be very helpful as well. So, you mentioned mentioning to the neuroradiologist that we're looking for a cause of seizures or epilepsy and epilepsy protocols or MRI. What is sort of the nature of those protocols if there's not a quote unquote “ready-made” one at someone 's center in their practice or in their local MRI center? What types of things can be communicated to the radiologist as far as particular sequences or types of images that are helpful in this scenario? Dr Skidmore: I spent a fair amount of time in the article going over the specific MRI protocol that was designed by the International League Against Epilepsy. But what I look for in an epilepsy protocol is a high-resolution T2 coronal, a T2 flare weighted image that really traverses the entire temporal lobe from the temporal tip all the way back to the most posterior aspects of the temporal lobe, kind of extending into the occipital lobe a little bit. I also want to see a high resolution. In our center, it's usually a T1 coronal image that images the entire brain with a very, very thin slice, and usually around two millimeters with no gaps. As many of our neurology colleagues are aware, when you get a standard MRI of the brain for a stroke or a brain tumor, you're going to have a relatively thick slice, anywhere from five to eight millimeters, and you're actually typically going to have a gap that's about comparable, five to eight millimeters. That works well for large lesions, strokes, and big brain tumors, but for some of the tiny lesions that we're talking about that can cause intractable epilepsy, you can have a focal cortical dysplasia that's literally eight- under eight millimeters in size. And so, making sure you have that nice T1-weighted image, very thin slices with no gaps, I think is critical to make sure we don't miss these more subtle abnormalities. Dr Berkowitz: Some of the entities you describe in your paper may be subtle and more familiar to pediatric neurologists or specialized pediatric neuroradiologists. It may be more challenging for adult neurologists and adult neuradiologists to recognize, such as some of the various congenital brain malformations that you mentioned. What's your approach to looking for these? Which sequences do you focus on, which planes? How do you use the patient 's clinical history and EEG findings to guide your review of the imaging? Dr Skidmore: It's very important, and the reason we're always looking for a lesion---especially in patients that we're thinking about epilepsy surgery---is because we know if there is a lesion, it increases the likelihood that epilepsy surgery is going to be successful. The approach is basically, as I mentioned a little bit before, is take all the information you have available to you. Is the seizure semiology, is it a hyper motor semiology or hyperkinetic semiology suggestive of frontal lobe epilepsy? Or is it a classic abdominal rising aura with automatisms, whether they be manual or oral automatisms, suggesting mesial temporal lobe epilepsy? And so, take that clinical history that you have to help start to hone your eye into those individual locations. But then, once you're kind of looking in these nonlesional cases, you're also then looking at the EEG and where their temporal lobe spikes, where their frontal lobe spikes, you know, using that and pulling that information in. If they saw a neuropsychologist pulling in the information in from the neuropsychological evaluation; if they have severe reductions in verbal memory, you know, focusing on the dominant temporal lobe. So, in a right-handed individual, typically the left temporal lobe. And kind of then really spending a lot of time going slice at a time, very slowly, because in some of these vocal-cortical dysplasias it can be just the blurring of the gray-white margin. What I find easiest is to identify that gray-white margin and almost track it. Like, you use the mouse to kind of track it around and say, can I outline the exact border of the gray white margin in the frontal lobe that I'm interested in or the temporal lobe that I'm interested in, kind of looking for those subtle abnormalities. Often as neurologists, we don't have the luxury of being able to immediately reformat. As I mentioned, our T1 volume acquisition study is done in the coronal plane, but sometimes you might want it in the axial plane. And so, I might reach out to the radiologist and say, hey, can you reformat this in the axial plane because I'm interested in the frontal lobe epilepsy and it's a little bit better at looking at it in that plane? And I'll have them reformat and put it back on the pack so I can look at it in that manner. And so that's a, kind of another strategy is to take what you have, but also then go back to the radiologist and say, I need to look at it this a different way. Can you reformat it for me? Looking for that gray-white matter junction is the nice way to pick up for kind of subtle cortical dysplasias. And then when you see an abnormality, to be able to put the T1, the T2, and the flare image all up next to each other and use the technology built into most of our browsers to put on what's called the localizer mode, where I can highlight a specific spot that I'm seeing on the T1 and then very easily quickly see, what does it look like on the T2? What does it look like on the flare? To kind of quickly decide, is it a true abnormality or am I only seeing it on one slice because of an artifact on that one imaging sequence? And I think that's the biggest kind of key is to make sure, is it an artifact or is it not an artifact? That's kind of the most common thing that we, I think, get confused with. Dr Berkowitz: So, some very helpful pearls there in terms of reviewing the imaging, being in dialogue with our neuroradiology colleagues to think about potentially reacquiring certain images on certain planes or looking at the images with our neuroradiology colleagues to let them know more about the clinical history and where we're sort of zooming in about possible abnormalities. Dr Skidmore: I would just add in there that when looking at especially the mesial temporal structures, because of a lot of artifacts that can be present in an individual MRI machine, it's not uncommon that the mesial temporal structure will appear brighter because of an MRI magnet artifact. And so, it's a good key to look at the hippocampus compared to the insula. And so, the hippocampus and the insula should have similar signal characteristics. You're seeing the hippocampus is bright, but the insula ipsilateral to it’s normal intensity. That would suggest that that's probably a true hyperintensity on the flare-weighted image as opposed to if both are bright, unless you're suspecting a hemispheric abnormality, it's more likely to be a kind of artifact in the MRI machine. Dr Berkowitz: Okay. Those are really helpful tips, not just to analyze the hippocampus and medial temporal lobe itself---let's remember our anatomy and the circuit of Papez---and to look at associated structures for supporting evidence of a possible abnormality in the hippocampus itself. It looks like there may be something subtle. We can use some additional information from the image to try to decide if that is real or artifactual, and of course correlating with the clinical picture and EEG. I'd like to talk briefly now about some other imaging modalities that you discuss in your paper, the use of functional imaging such as PET, SPECT and fMRI. Let's talk a bit about each of these. When would you order a PET scan for a patient with epilepsy? What would you be looking for and how would you be using that to make clinical decisions? Dr Skidmore: Yeah, so these functional imaging modalities are really utilized when we're evaluating somebody that's not responding to medications. So, they're medically intractable, and we're wondering, could they be a candidate for epilepsy surgery? And so, most of these imaging modalities are really relegated to the world of epileptologists at surgical epilepsy centers. I wanted to include them, though, in the article because I do think it's important for general neurologists to understand kind of what they are, because invariably a patient sees me and then they go back to their general neurology and be like, hey, Doctor Skidmore said I had this PET scan abnormality. What do you think? So, I think it's a good idea for general neurologists to kind of understand them. So, probably the oldest that we've utilized is the FDG PET scan, basically looking at fluorodeoxyglucose and the brain's utilization of glucose. As we all remember, again, glucose is the primary molecule for energy and ATP production in the brain. And so basically, by injecting radioactive glucose in the interictal state--- so not during a seizure but in between seizures---areas of the brain that are not taking up the radiotracer will show as being hypometabolic. So, low metabolism. And hypometabolic regions in the interictal state have been associated with onset regions for epileptic seizures. Let's say you have a patient clinical history, you think they have temporal of epilepsy, EEG suggests temporal of epilepsy, but the MRI is nonlesional, meaning there's no abnormality that anybody could appreciate even at a 3 Tesla scanner. We'll get an FDG PET scan and see, is there hypo metabolism in that temporal lobe of interest? And if there is, well, that's been shown through several published papers, that's just as valuable as having an abnormality on the MRI. And so, we often again use these PET scans, especially in nonlesional cases, to try to find that subtle cortical dysplasia. Now you have your nice epilepsy protocol MRI, it says it's nonlesional. You get your PET scan, it shows hypometabolism in a region of the frontal lobe, let's say, in a in a frontal lobe epilepsy case. And then often we go back, we kind of talked about strategy of how you find those subtle lesions. Then you go back and say, well, look, this gyrus specifically on the PET scan said it's abnormal. You end up looking for really subtle, very tiny abnormalities that, even with somebody that's skilled, often at first review gets missed. So, that's how we use the PET scan. The SPECT scan is done typically in the ictal state. So, now somebody’s in an epilepsy monitoring unit often, where you're injecting radio tracer at the exact moment that somebody starts having a seizure. And we know when there's increased seizure activity, the increased seizure activity---let's say it's from my right temporal lobe---is going to increase cerebral blood flow transiently to the right temporal lobe. And then if that seizure discharge spreads from the right temporal lobe maybe to the entire right hemisphere and eventually becomes a focal to bilateral tonic chronic seizure by spreading to the other side, the entire brain is going to be hypoperfused at that point. So, if you want to, as soon as the seizure starts, inject that radio tracer to see, where is the blood flow earliest in the seizure? And then we might do an interictal SPECT when you're not having a seizure. Look at, all right, what's the normal blood flow when somebody's not seizing? What's it like when they're having a seizure? And then the area that has increased activity would- might suggest that's where the seizure started from. But we have to be very careful because again, some seizures can spread very rapidly. So, if you delay injecting an injection ten, fifteen, twenty seconds, the seizure could have already propagated to another region of the brain, giving you a false positive in another location. So, you have to be very careful about that modality. I think what's most exciting is the functional MRI because the functional MRI, for many, many centers, is replacing a very old technique called the WADA test. So, in the WADA test, typically you place a catheter angiogram into the internal carotid artery and transiently introduce a sedative medication to put, let's say, the left hemisphere to sleep because you wanted to see what functions were still active in the right hemisphere. And then the surgeon would move the catheter or the right internal carotid artery, and you inject a sedative on that side after the left hemisphere is recovered and see what the left hemisphere can do. And we used that for language dominance, we used that for memory dominance. And while most individuals did fine with angiograms, unfortunately complications do occur and there's injury to the artery, there could be strokes that can- that have happened, which can be quite devastating for the patient. And so, functional MRI is a nice, noninvasive way for us to map out language function, motor function, sensory function, visual function, and is starting to show some usefulness also for mapping out kind of memory function, dominant memory function, meaning verbal memory compared to visual memory. To be able to do those things noninvasively becomes really important because, if we're talking about epilepsy surgery, we want to make you seizure-free but neurologically intact. And so, we need to understand the relationship between where we think the seizures are coming from and where eloquent cortex is so we can properly counsel you and avoid those regions during any planned surgery. Those are the three most common functional imaging modalities that we're using now to supplement the rest of the presurgical work. Dr Berkowitz: Very helpful. So, these are studies, PET, SPECT, and fMRI, that would really be obtained predominantly in patients in whom epilepsy surgery was being considered to have more precise lesion localization, as well as with the fMRI to get a better sense of how to provide the safest maximal resection of epileptogenic tissue while preserving functions. Dr Skidmore: That's a perfect summary. Dr Berkowitz: Fantastic. This has been a really helpful interview with Dr Skidmore and a really fantastic article. As I said, a picture is worth a thousand words, so I definitely encourage... /episode/index/show/continuumjournal/id/34884105

EEG in Epilepsy With Dr. Daniel Weber 02/12/2025

EEG in Epilepsy With Dr. Daniel Weber EEG is the single most useful ancillary test to support the clinical diagnosis of epilepsy, but if used incorrectly it can lead to misdiagnosis and long-term mental and physical health sequelae. Its application requires proper understanding of its limitations and variability of testing results. In this episode, Katie Grouse, MD, FAAN, speaks with Daniel Weber, DO, author of the article “EEG in Epilepsy,” in the Continuum® February 2025 Epilepsy issue. Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California. Dr. Weber is the director of adult epilepsy and vice chair of clinical affairs at the St. Louis University in St. Louis, Missouri. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Guest: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Grouse: This is Dr Katie Grouse. Today, I'm interviewing Dr Daniel Weber about his article on EEG and epilepsy, which appears in the February 2025 Continuum issue on epilepsy. Welcome to the podcast and please introduce yourself to our audience. Dr Weber: Hi, thanks for having me. My name is Dan Weber and I'm an epileptologist at Saint Louis University. I direct the adult epilepsy program here and also serve as the vice chair for Clinical Affairs. Been my pleasure to work on this article. Dr Grouse: I'm so happy to have you today. I read your article. I found it to be incredibly useful as someone who often orders EEG in the general neurology clinic. So, I wanted to start with asking, what is the most clinically relevant message or takeaway from your article that you'd really like neurologists to know? Dr Weber: Yes, when I was asked to write this article, I looked back at the previous Continuum on epilepsy and just the general literature. And there's a lot of good articles and books out there on EEG and epilepsy and sort of giving you a primer on what you might see and how to interpret it. So, we wanted to try to go a slightly different direction. This article gives you some of that gives you the background of EEG and some of the basic things that you may see, but the real thrust of it is more about the limitations of EEG in the clinical picture of epilepsy and common things you might avoid. There are some things that we get hammered into our brains in training that aren't always true and there's plenty of examples in the literature to review, and this article sort of tries to encapsulate as many of those as possible in a digestible format. The main takeaway would be that EEG is an extremely helpful tool in the diagnosis of epilepsy, is the best tool we have to help supplement your clinical acumen. But it does not make the diagnosis of epilepsy. And there are certain circumstances when it may not be as helpful as you may have been led to believe in residency. Dr Grouse: Maybe not the most comforting of messages, but certainly an important one, very important to learn more about this. So, we appreciate that. Can you tell us your decision-making process when deciding whether to order a routine EEG, an extended EEG, prolonged ambulatory EEG, or inpatient video EEG? Dr Weber: Sure. So, it's a multi-part question because each one, I think, has a different clinical scenario. In the current state, our best data for estimating risk of recurrence after an initial seizure comes with routine EEG abnormalities. So, often I will order routine EEGs in those scenarios. So new patient presentation, new patients coming in with an initial seizure who want to know what's their risk of recurrence. So, risk stratification, I use a lot of routine EEG for, often sleep deprived if possible to increase the sensitivity. If you'd like, the extended EEG does offer higher sensitivity, or you can repeat the routine EEG if the first routine EEG is nonconclusive. For generally extended EEGs, I tend to order them in my practice if patients have come to see me with a suspected diagnosis of epilepsy but haven't yet had any electrographic confirmation. Maybe they've already had routine EEGs done in the past, so we'll try to obtain just a little more data. The longer-term EEGs I tend to use in different clinical scenarios, in patients usually who already have established diagnosis or people who have become refractory and we haven't yet confirmed their diagnosis. I tend to do inpatient EEGs in those situations. Ambulatory EEGs I do more when there are certain characteristics of the patient or the patient 's presentation that may not fit well on the inpatient side. Patients who are reliant on substances who can't use while they're inpatient and may have withdrawal effects complicating the stay. Or people who have a strong activation component to their epilepsy where activity really draws it out, certain activities that they do at home that they might not do during the inpatient stay. Those are the sorts of people I'll do ambulatory EEGs on. There are a couple other scenarios as well that come up less commonly, but everything has its own little niche. Dr Grouse: That's a really helpful review as we sort of think about which way we want to go as we're working up our patients in the inventory setting. Can you tell me a little more about the difference between sensitivity of, for instance, doing maybe two routine EEGS versus prolonged ambulatory EEG? Dr Weber: Generally speaking, the longer you're recording someone's brain waves, the higher the sensitivity is going to be. So routine EEG is twenty to forty minutes at most places. One of those gives you a certain sensitivity. More of them will give you more sensitivity. And there was a recent study highlighted in the article that compared routine EEGs to initial multi-day ambulatory EEG, and the ambulatory EEG obviously, as would be expected, has a higher sensitivity than either of the routines. So, there may be some cases with that initial evaluation where an ambulatory EEG may be held and we get into that in more detail in the article. But with the caveat, a lot of this article is about limitations, and the data that we have to talk about increased risk of recurrence was based off seeing epileptic form discharges on routine EEG. So you could hypothesize that if you only have one epileptic form discharge in three days on an ambulatory EEG, that may not carry the same recurrent significance as catching one on a twenty minute EEG. But we don't have that knowledge. Dr Grouse: Getting a little bit more into what you mentioned about the limitations, when is the scalp EEG less useful or limited in the evaluation of epilepsy? Dr Weber: So, one thing I see a lot in my residence at here and other places where I've worked is, I get them very excited about EEG and they may order it a bit too much. So, if patients have a known, established diagnosis of epilepsy, electrographically confirmed, and they come in with a breakthrough seizure and they're back to their baseline, there's really not a strong reason to get an EEG. We often seem to in the emergency department as part of our evaluation, but we already know what happened to the patient. The patient's not doing poorly right now, so the EEG is not going to give you any additional information. Just like really any test, you should think, what are the possible outcomes of this test and how would those outcomes alter the care of this patient? And if no outcome is going to affect the care of the patient or give you any additional diagnostic information, then probably don't need to be doing that test. Dr Grouse: This is probably a good segue into asking, what is an area of confusion or common pitfalls that you've seen in the clinical application of EEG and epilepsy? Dr Weber: So, a lot of times on the inpatient service, we'll get longer-term EEGs for patients who are having spells that are occurrent while they're in the ICU or other places or altered in some way, encephalopathic. And these patients will have their spell, and in my report, I'll say that there is not any electrographic correlate. So, there's no EEG finding that goes along with the movement that they're doing that's concerning for a seizure. And that doesn't always mean that it's not an epileptic seizure. An EEG is not a one-hundred-percent tool. Epilepsy and seizures are a clinical diagnosis. The EEG is a helpful tool to guide that diagnosis, but it is not foolproof, so you need to take the whole clinical picture into account. Particularly focal seizures without impaired awareness often can be electrographically silent on surface EEG. If you see something that looks clinically like a seizure but doesn't show up on the EEG, there are circumstances that they get to in the paper a little bit where that can still be an epileptic seizure. And you just have to be aware of the limitations of the tests that you're ordering and always fall back on the clinical skills that you've learned. Dr Grouse: Are there any tips or tricks you can suggest to improve the clinical utility of EEG for diagnosis of epilepsy? And also thinking about the example you just gave, but maybe other cases as well? Dr Weber: Again, definitely need to incorporate EEG as part of a larger picture. The video component of EEG is incredibly helpful. You can't interpret EEG in isolation. Regardless of what the EEG shows, you can't make a diagnosis of epilepsy, but you certainly can be very suspicious of one. So, in those cases where you have a high suspicion for an epileptic seizure and the EEG has not given you any confirmatory evidence, it's really helpful to rely on any clinical expertise that you have access to. So, people who have seen lots of seizures may be helpful in that situation. Getting good recordings, good data to prove yourself one way or the other is helpful and continuing to evaluate. So usually, as I said, focal seizures that don't show up well on the EEG. People who have focal seizures will often have larger seizures if left untreated. So, you can try to admit them to an epilepsy monitoring unit where we try to provoke seizures and try to provoke a larger seizure to help confirm that diagnosis. Dr Grouse: This kind of gets into what we've already reviewed to some degree, but what is the easiest mistake to make (and hopefully avoid) when using EEG to diagnose epilepsy or make other treatment decisions? Dr Weber: I think the easiest, most common mistake I see is overreliance on the test. There's a lot of subjectivity to the interpretation of this test. There are a lot of studies out there on interrater reliability for epilepsy and intrarater reliability for epilepsy. We continue to try to make the findings more objective and get more quantified. The articles talk about our six criteria for epileptiform discharges and have reference to where that came from and the sorts of specificity that each of those criteria lead to. Just because an EEG report has said something, that does not diagnose or negate a clinical diagnosis of epilepsy. It is common for folks with non-epileptic seizures to have a history of reported epileptic form discharges on their EEG. Again, because there is some subjectivity to the test, some abnormal-looking normal variants will pop up and get interpreted as epileptiform discharges. It's important to review the whole patient, as much of the data as you can, and make the best clinical judgment you can of the overall case. Dr Grouse: What is quantitative EEG and how can it be clinically useful? Dr Weber: Now that most EEG is obtained digitally through the use of computer software, we have been able to employ computers to do a lot of the work for us. There are many different ways of looking at the EEG data, but it's all frequency bands over time. The quantitative EEG goal is really to simplify and condense what you're seeing on your normal EEG page into a more digestible format. Lets you look at a larger amount of data faster, which becomes more and more important as we're doing more of these long-term recordings, particularly in the intensive care unit. Quantitative EEG can help you assess a lot of data at a snapshot and get a general sense of what's going on with the patient over the past several hours. It does require some extra training to become familiar with it, but it's training that can be done at all levels. Again, it can help you see more, faster. Obviously, like everything, it has its own limitations. Sometimes the sensitivity and specificity may be a little off from the raw data review, and you should always go back to the raw data anytime there are questions. But it can be helpful to make things faster. Dr Grouse: Do you think you could give me a hypothetical example of a case where this would be something really nice to have? Dr Weber: The most common example is folks with repetitive seizures in the ICU. If you're just looking at the raw data, you will get a sense of how often the seizures are happening. But if you look at the quantitative data, it sort of compresses that all down to a much smaller snapshot. So you can see much more readily, yes, these are how many seizures were happening. And here's where we gave our intervention; and look, there are fewer seizures after that intervention. So, it can help you assess response to treatment, help you assess just overall volume of seizures in a much more condensed fashion, and you can get through it much faster with the appropriate training. Dr Grouse: Can you tell us about any new developments in EEG that are on the horizon we should be aware of? Dr Weber: Yeah. So, I think my two favorites, which I highlight in the article, are longer-term recordings---so, there's some companies that are working on subcutaneous EEG. So, implanted EEG electrodes that can stay in your body for the short, long term on the order of year or years and constantly send some EEG data. Obviously, it's not a full montage in most of those cases, but some EEG data that can help you assess long-term trends in epilepsy and long-term response to therapies. I think that's going to be really cool. I think it's very exciting and I think it'll change how we do clinical trials in the future. I think we'll be able to rely less on seizure diaries from folks and more on objective seizure data for patients who have these implanted. But with that will come an ever-increasing amount of data to be reviewed, which leads into the other exciting future trend is AI in the use of interpretations. AI is becoming more and more advanced and there are very exciting articles out on how good AI is getting at interpreting our EEGs. I think soon, in the very near future, the AI platforms will be able to dramatically reduce the amount of time it takes the experts to review an EEG. They'll be able to do a lot of the screening for us and then we can go back, just like I was talking about the quantitative EEG, go back and review segments of the raw data rather than having to review every page of every file, which is quite time consuming. Dr Grouse: Wow, that's really exciting. It certainly does seem like AI is making breakthroughs in just about every area of how we touch the practice of medicine. Exciting to hear that EEG is no exception. Dr Weber: Yeah, I'm fully excited. I think it's going to revolutionize what we're doing and also just greatly expand people's ability to access that level of expertise that the AI will offer. Dr Grouse: I wanted to transition to talking a little bit more about you and your career in neurology. How did you become interested in this area of neurology to begin with? Dr Weber: Yeah, it's sort of a roundabout fashion. So, I started out planning to be a neurointerventionalist, and then I realized that I didn't want that sort of call. For a hot minute in my PGI 3 year. I was planning to be a neuro-ICU doctor. I think that's largely because medicine is all I had been exposed to at that point and the ICU seemed like a very comfortable place. Then as I transitioned into PGI 3 we started doing more electives and outpatient rotations in my residency. And then I was planning on being a movement disorder specialist or an epileptologist, couldn't make up my mind for the longest time. And then I started to like EEG more than I liked watching videos. So, tilted myself towards epilepsy and haven’t looked back. Dr Grouse: Well, I really appreciated you coming to talk with us today about your article. I can't recommend it enough to anyone out there, whoever treats patients with epilepsy or orders the EEGs, I just think it was just incredibly useful. And it was such a pleasure to have you. Dr Weber: Thank you very much for having me, Katie. Dr Grouse: Again, today I've been interviewing Dr Daniel Weber about his article on EEG and epilepsy, which appears in the most recent issue of Continuum on Epilepsy. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio. /episode/index/show/continuumjournal/id/34884075

Classification and Diagnosis of Epilepsy With Dr. Roohi Katyal 02/05/2025

Classification and Diagnosis of Epilepsy With Dr. Roohi Katyal Epilepsy classification systems have evolved over the years, with improved categorization of seizure types and adoption of more widely accepted terminologies. A systematic approach to the classification of seizures and epilepsy is essential for the selection of appropriate diagnostic tests and treatment strategies. In this episode, Aaron Berkowitz, MD, FAAN, speaks with Roohi Katyal, MD, author of the article “Classification and Diagnosis of Epilepsy,” in the Continuum February 2025 Epilepsy issue. Dr. Berkowitz is a Continuum® Audio interviewer and a clinical professor of neurology at the University of California, San Francisco. Dr. Katyal is an assistant professor of neurology and codirector of adult epilepsy at Louisiana State University Health Shreveport in Shreveport, Louisiana. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Guest: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum Journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Berkowitz: This is Dr Aaron Berkowitz, and today I'm interviewing Dr Roohi Katyal about her article on classification and diagnosis of epilepsy, which appears in the February 2025 Continuum issue on epilepsy. Welcome to the podcast, Dr Katyal, and could you please introduce yourself to our audience? Dr Katyal: Thank you for having me. I'm very excited to be here. I'm Dr Roohi Katyal. I currently work as Assistant Professor of Neurology at LSU Health Shreveport. Here I also direct our adult epilepsy division at LSU Health along with my colleague, Dr Hotait. Dr Berkowitz: Fantastic. Well, happy to have you here. Your article is comprehensive, it's practical, and it focused on explaining the most recent International League Against Epilepsy (ILAE) classification of epilepsy and importantly, how to apply it to provide patients with a precise diagnosis of epilepsy and the particular subtype of epilepsy to guide the patient's treatment. There are so many helpful tables and figures that demonstrate all of the concepts and how to apply them at the bedside. So, I encourage our listeners to have a look at your article, even consider maybe screenshotting some of these helpful tables onto their phone or printing them out for handy reference at the bedside and when teaching residents. Your article begins with the current definition of epilepsy. So, I want to ask you about that definition and make sure we're on the same page and understand what it is and what it means, and then talk through a sort of hypothetical patient scenario with you to see how we might apply these in clinical practice. You talked about, in your article, how the new definition of epilepsy from the ILAE allows for the diagnosis of epilepsy in three different scenarios. So, could you tell us what these scenarios are? Dr Katyal: So, epilepsy in general is a chronic condition where there is a recurrent predisposition to having seizures. As you mentioned, epilepsy can be diagnosed in one of three situations. One situation would be where an individual has had two or more unprovoked seizures separated by more than 24 hours. The second situation would be where somebody has had one unprovoked seizure and their risk of having recurrent seizures is high. And the third situation would be where somebody had---where the clinical features could be diagnosis of an epilepsy syndrome. An example of that would be a young child presenting with absence seizures and their EEG showing 3 Hz characteristic generalized spike in with discharges. So that child could be diagnosed with childhood absence epilepsy. Dr Berkowitz: Perfect. Okay, so we have these three scenarios, and in two of those scenarios, we heard the word unprovoked. Just to make sure everyone's on the same page, let's unpack this word “unprovoked” a little bit. What does it mean for a seizure to be unprovoked versus provoked? Dr Katyal: So unprovoked would be where we don't have any underlying provoking features. So underlying provoking features are usually reversible causes of epilepsy. These would be underlying electrolyte abnormality, such as hyperglycemia being a common one which can be reversed. And these individuals usually do not need long-term treatment with anti-seizure medications. Dr Berkowitz: Fantastic. Tell me if I have this right, but when I'm teaching residents, I… did it provoked and unprovoked---there's a little confusing, right? Because we use those terms differently in common language than in this context. But a provoked seizure, the provoking factor has to be two things: acute and reversible. Because some people might say, well, the patient has a brain tumor. Didn't the brain tumor provoke the seizure? The brain tumor isn't acute and the brain tumor isn't reversible, so it would be an unprovoked seizure. I always found that confusing when I was learning it, so I try to remind learners I work with that provoked means acute and reversible, and unprovoked means it's not acute and not reversible. Do I have that right? Am I teaching that correctly? Dr Katyal: That's correct. Dr Berkowitz: Great. And then the other important point here. So, I think we were all familiar prior to this new guideline in 2017 that two unprovoked seizures more than twenty-four hours apart, that's epilepsy. That's pretty straightforward. But now, just like we can diagnose MS at the time of the first clinical attack with the right criteria predicting that patient is likely to have relapse, we can say the patient’s had a single seizure and already at that time we think they have epilepsy if we think there's a high risk of recurrence, greater than or equal to sixty percent in this guideline, or an epilepsy syndrome. You told us what an epilepsy syndrome is; many of these are pediatric syndromes that we've studied for our boards. What hertz, spike, and wave goes with each one or what types of seizures. But what about this new idea that a person can have epilepsy after a single unprovoked seizure if the recurrence rate is greater than sixty percent? How would we know that the recurrence rate is going to be greater than sixty percent? Dr Katyal: Absolutely. So, the recurrence rate over sixty percent is projected to be over a ten year period. So, more than sixty percent frequency rate in the next ten years. And in general, we usually assess that with a comprehensive analysis and test. So, one part of the comprehensive analysis would be, a very important part would be a careful history taking from the patient. So, a careful history should usually include all the features leading up to the episodes of all the prodromal symptoms and warning signs. And ideally you also want to get an account from a witness who saw the episode as to what the episode itself looked like. And in terms of risk assessment and comprehensive analysis, this should be further supplemented with tests such as EEG, which is really a supportive test, as well as neuroimaging. If you have an individual with a prior history of, let's say, left hemispheric ischemic stroke and now they're presenting with new onset focal aware seizures with right arm clonic activity, this would be a good example to state that their risk of having future seizures is going to be high. Dr Berkowitz: Perfect. Yeah. So, if someone has a single seizure and has a lesion, as you said, most common in high-income countries would be a prior stroke or prior cerebrovascular event, prior head trauma, then we can presume that the risk is going to be high enough that we could call that epilepsy after the first unprovoked seizure. What if it's the first unprovoked seizure and the imaging is unremarkable? There's no explanatory lesion. How would we get to a diagnosis of epilepsy? How would we get to a risk of greater than sixty percent in a nonlesional unprovoked seizure? I should say, no lesion we can see on MRI. Dr Katyal: You know, in those situations an EEG can be very helpful. An EEG may not always show abnormalities, but when it does show abnormalities, it can help us distinguish between focal and generalized epilepsy types, it can help us make the diagnosis of epilepsy in certain cases, and it can also help us diagnose epilepsy syndromes in certain cases. Dr Berkowitz: Perfect. The teaching I remember from a resident that I'm passing on to my residents, so please let me know if it's correct, is that a routine EEG, a 20-minute EEG after a single unprovoked seizure, this sensitivity is not great, is that right? Around fifty percent is what I was told with a single EEG, is that right? Dr Katyal: Yeah, the sensitivity is not that great. Again, you know, it may not show abnormality in all the situations. It's truly just helpful when we do see abnormalities. And that's what I always tell my patients as well when I see them in clinic. It may be abnormal or it may be normal. But if it does show up normal, that does not rule out the diagnosis of epilepsy. Really have to put all the pieces together and come to that finally diagnosis. Dr Berkowitz: Perfect. Well, in that spirit of putting all the pieces together, let's walk through together a hypothetical case scenario of a 19-year-old patient who presents after a first event that is considered a possible seizure. First, how do you approach the history and exam in this scenario to try to determine if you think this was indeed an epileptic seizure? Dr Katyal: So, if I'm seeing them in the clinic or in the outpatient setting and they're hopefully presenting with somebody who's already seen the seizure itself, my first question usually is if they had any warning signs or any triggers leading up to the episode. A lot of times, you know, patients may not remember what happened during the episode, but they may remember if they felt anything different just before or the day prior, something different may have happened around that time. Yeah, so they may report that. Then a very important aspect of that would be talking to somebody who has seen the episode, a witness of the episode; and ideally somebody who has seen the onset of the episode as well, because that can give us very important clues as to how the event or the episode started and how it progressed. And then another very important question would be, for the individual who has experienced it, is how they felt after the episode ended. So, you can get some clues as to if they had a clear postictal state. Other important questions would be if they had any tongue biting or if they lost control of their bladder or all those during the episode. This, all those pieces can guide us as to if the seizure was epileptic, or the episode was epileptic or not. Dr Berkowitz: Fantastic. That's very helpful guidance. All right. So, let's say that based on the history, you're relatively convinced that this patient had a generalized tonic clonic seizure and after recovering from the event, you do a detailed neurologic exam. That's completely normal. What's your approach at this point to determining if you think the seizure was provoked or unprovoked, since that's, as you said, a key component of defining whether this patient simply had a seizure, or had a seizure and has epilepsy? Dr Katyal: The important findings would be from the laboratory test that may have been done at the time when the patient first presented with the seizure. So, we want to rule out features like hypoglycemia or other electrolyte abnormalities such as changes in sodium levels or big, big fluctuations there. We also want to rule out any other metabolic causes or other reasons such as alcohol withdrawal, which can be a provoking factor. Because these would be very important to rule out is if we find a provoking reason, then this individual may not need to be on long term anti-seizure medication. So very important to rule that out first. Dr Berkowitz: Great. So, let's say you get all of your labs and history and toxicology screen and no provoking factors there. We would obtain neuroimaging to see if there's either an acute provoking factor or some type of lesion as we discussed earlier. Let's say in this theoretical case, the labs are normal, the neuroimaging normal. There is no apparent provoking factor, there's no lesion. So, this patient has simply had a single unprovoked seizure. How do we go about now deciding if this patient has epilepsy? How do we try to get ourselves to either an above sixty percent risk and tell this patient they have epilepsy and probably need to be on a medicine, or they have a less than sixty percent risk and that becomes a little more tricky? And we'll talk about that more as well. Dr Katyal: For in a young patient, especially in a young patient as a nineteen year old as you present, one very important aspect if I get this history would be to ask them about absolutely prior history of similar episodes, which a lot of times they may not have had similar episodes. But then with this age group, you also want to ask about episodes of brief lapses in awareness or episodes of sudden jerking or myoclonic jerking episodes. Because if you have brief lapses of awareness, that could signify an absence seizure in this particular age group. And brief, sudden episodes of myoclonic jerking could be brief myoclonic seizures in this age group. And if we put together, just based on the clinical history, you could diagnose this patient with a very specific epileptic syndrome, which could be juvenile myoclonic epilepsy in the best case. Let's say if you ask about episodes of staring or relapses of awareness, that's not the case, and there's no history of myoclonic jerking episodes or myoclonic seizures, then the next step would be proceeding to more of our supplemental tests, which would be an EEG and neuroimaging. In all cases of new-onset seizure especially should have comprehensive assessment with EEG and neuroimaging to begin with, and we can supplement that with additional tests wherever we need, such as genetic testing and some other more advanced testing. Dr Berkowitz: That's very helpful. OK, so let's say this particular patient, you talk to them, you talk to their family, no prior history of any types of events like this. No concerns for spells that could---unlike absence, no concern for movements that could sound like myoclonus. So, as you said, we would be looking for those and we could get to part one of the definition. There is more than one spell, even though we're being consulted for one particular event. But let's say this was the only event, we think it's unprovoked, the neuroimaging is normal. So, you said we proceed to an EEG and as you mentioned earlier, if the EEG is abnormal, that's going to tell us if the risk is probably this more than sixty percent and the patient should probably be on a medicine. But common scenario, right, that the patient has an event, they have a full work up, we don't find anything. We're convinced it was a seizure. We get our routine EEG as we said, very good, an affirmative test, but not a perfectly sensitive test. And let's say this person's routine EEG turns out to be normal. So how would you discuss with the patient their risk of a future seizure and the considerations around whether to start an anti-seizure medicine if their work-up has been normal, they've had a single unprovoked seizure, and their EEG is unrevealing? Dr Katyal: And I'm assuming neuroimaging is normal as well in this case? Dr Berkowitz: Correct. Yeah. Dr Katyal: We have a normal EEG; we have normal neuroimaging as well. So, in this case, you know, it's more of a discussion with the patient. I tell them of that, you know, the risk of seizure may not be higher than sixty percent in this case with all the tests being normal so far and there's no other prior history of similar episodes. So, we have a discussion with them about the risks that can come with future seizures and decide where the medication should be started or not. Dr Berkowitz: And so how do you approach this discussion? The patient will say, Doctor Katyal, I had one seizure, it was very frightening. I got injured. You told me I can't drive for however many months. One cannot drive in that particular state. But I don't really like taking medicines. What is my risk and what do you think? Should I take a medicine? Dr Katyal: I'll tell you this because normally I would just have a direct conversation with them, discuss all the facts that we have. We go over the seizure one more time just to make sure we have not missed any similar episodes or any other episodes that may be concerning seizure, which ruled out all the provoking factors, any triggers that may be seen inseizures like this in a young age. And another thing would be to basically have a discussion with them, you know, these are the medication options that we can try. And if there is another seizure, you know, these are the these are the restrictions that would come with it. And it's a very individualized decision, to be honest. That, you know, not everyone may want to start the medication. And you'll also find that some patients who, you know, some individuals are like no, I want to go back to driving. I don't want to be in this situation again. I would like to try a medication and don't want to ever have a seizure. So, I think it's a very individualized decision and we have a discussion with the patient based on all of these tests. And I would definitely maintain follow-up with them to make sure that, you know, things have not changed and things have---no seizures have recurred in those cases. Dr Berkowitz: Yeah, great to hear your approach. And similar experience to you, right, where some patients say, I definitely don't want to take the medication, I'll roll the dice and I hope I don't have another seizure. And we say, we hope so also. As you said, let's keep a close eye. And certainly, if you have another seizure, it's going to be a lifelong seizure medicine at that point. And some patients who, as you said, say, wait, I can't drive for months. And if I don't take a medicine and I have a seizure in the last month, I would have to have another period of no driving. Maybe in that case, they would want to start a medicine. That said, we would present that either of these are reasonable options with risks and benefits and these are the medications we would offer and the possible side effects and risk of those, and make a joint decision with the patient. Dr Katyal: Absolutely correct. Mentioned it perfectly well that this is a very individualized decision and a joint decision that we make with the patient. Dr Berkowitz: Fantastic. Another topic you touch on in your article is the definition of resolved epilepsy. How is that defined in the guidelines? Dr Katyal: Yes. So, an epilepsy can be considered resolved if an individual has been seizure-free for at least ten years and has been off of IV seizure medications for at least five of those years. Another situation where epilepsy can be considered resolved would be if they have an age-defined epilepsy syndrome and now they are beyond the relevant age group for the syndrome. Dr Berkowitz: That's very helpful. So again, a very clear definition that's... /episode/index/show/continuumjournal/id/34883995

February 2025 Epilepsy Issue With Dr. Jennifer Hopp 01/29/2025

February 2025 Epilepsy Issue With Dr. Jennifer Hopp In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Jennifer L. Hopp, MD, FAAN, FAES, FACNS, who served as the guest editor of the Continuum® February 2025 Epilepsy issue. They provide a preview of the issue, which publishes on February 3, 2025. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Hopp is a professor in the department of neurology at the University of Maryland School of Medicine in Baltimore, Maryland. Additional Resources Continuum website: Subscribe to Continuum: More about the American Academy of Neurology: Social Media Host: Guest: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology, clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum who are the leading experts in their fields. Subscribers to the Continuum Journal have access to exclusive audio content not featured on the podcast. If you're not already a subscriber, we encourage you to become one. For more information, please visit the link in the show notes Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, Lifelong Learning in Neurology. Today I'm interviewing Dr Jennifer Hopp, who recently served as Continuum's guest editor for our latest issue on epilepsy. Dr Hopp is a professor and executive vice chair in the Department of Neurology at the University of Maryland School of Medicine, where she's also director of the Epilepsy Center. Dr Hopp, welcome. Thank you for joining us today. Why don't you introduce yourself to our listeners? Dr Hopp: Hi, Dr Jones. Thank you so much for having me on this podcast. I really had so much fun working with you and other authors of this issue and serving as editor. I feel like it was yesterday that I was author of an article in the past. And so, it's really a pleasure to take on this new role and create the content for the issue of Continuum for Epilepsy and really particularly to work with the stellar group of experts and authors that we were able to have us join this year. Dr Jones: I want to thank you for, really, it's a remarkable issue. And we usually don't get into this a lot with our guest editors, but our last issue on epilepsy came out in 2022. Fantastic issue, guest edited by Dr Natalie Jette. When you were designing the table of contents and article topics for this issue, you had some great ideas. Walk us through your thought process on what was most important to convey in this issue. Dr Hopp: Sure, I'm happy to do so. I think one of the things about Continuum that is so accessible to everybody is that it really is, to me, preeminent format of updating and educating, whether it's epileptologist, neurologist, trainees in every area of epilepsy, which is obviously an enormous task to really pull together all of these data to make updates and then to make it accessible to all of these different levels of learners as well as people like myself. I really read and always look forward to all the Continuum issues outside of my field. I use it to update my knowledge base, get ready for boards. I also read it as an educator because I want to know what my trainees are reading during their rotations and I want to be able to share materials with them. So, I really tried to go back and look at other issues and think about how we could make it fresh. So, I think one of the first challenges is just making sure that we're updating the content of each article based on the literature and the data we have. That really becomes the task of the authors. And so first of all, selecting the authors was both fun but also really important to me. But the second aspect of it to me was really the question of, how could we make this fresh this year? I think Continuum is always fresh and that it has new data, but I wanted to really think outside the box and I appreciate being able to take a few risks. One of them was really headed by Dave Clarke, who provides this incredibly thoughtful and comprehensive review of access to care and epilepsy. I think for anyone who wants a primer on the issues and language used in discussions of diversity or social determinants of health---you first of all do not have to be in the field of epilepsy to read this. So, you should check that out. But I also thought it was really critical to shed more light on these issues. So, we tried to be mindful of this in threading that through as best as we could each article, but also have a stand-alone section that he headed. And so, he addresses issues of how to think about access to care for people with epilepsy, but actually, interestingly, also thinking about the investigators, providers, and researchers, and how we think about diversity in those viewpoints as well. I think we can always do better. Dave concludes with a wonderful focus on hope in this area with next steps for our community. So, I think that that was certainly one area that I wanted to take a risk and I think it was quite successful. Dr Jones: Totally agree. I very much enjoyed that article. We have an article on implementation of guidelines and quality measures by Dr Christina Baca. I thought that was a great choice from your perspective, not only because Dr Baca is an expert on this, but it felt very practical, right? Dr Hopp: Exactly. Exactly. And that was the other area that I thought really is always covered so well by the Academy of Neurology. There's so much work in updating the guidelines, whether it's the guideline that just was updated on people with epilepsy of childbearing potential or others outside of the field of epilepsy. And I thought that we could use Continuum to help educate all of the readers on how to take those guidelines and measures and then really bring them into practice. I think there's a whole field of implementation science that I think shines a light on the gap between the guidelines and the measures and then really what we do with them in practice. And that's actually what's most important for our patients and for the providers. And so Christine does just an amazing job as an expert, not only walking us through the guidelines that are relevant for epilepsy, but then helping us and providing, essentially, a toolkit to take those measures and guidelines and use them in a very feasible, accessible way in day-to-day practice. And I would suggest that it's relevant for anyone from a student level resident to an epileptologist who's been in practice, like me, for many years. And so I hope that's relatable and useful to the reader. Dr Jones: I think it will be. And let's get right into it. So, I always enjoy talking to the guest editor. You're already an expert and now you've just read a bunch of articles and edited a bunch of articles from people who are really the premier experts in their area of the field, right? They’re niche within epilepsy. So, as you've read these articles across the issue, if there were one biggest practice-changing recommendation that you would want to convey to our listeners, what would that be? Dr Hopp: I think that's a fabulous question because again, each of these articles, I think, is designed and written by the author to stand alone. But ideally, they need to all be incorporated in practice. And I think what each author was able to really successfully do is not only review the data, but really take us to the next level with practice of epilepsy. For example, I think as we embark on the next couple of decades, clearly increased technology, AI, personalized medicine are all buzzwords and taking the lead. In reality, with advances, we still have to make sure our care is personalized. And we have to remember seizures are really the symptom, but epilepsy is the disease. What I think our authors do well is make sure that our care is personalized to the patients. You could take that from the first article that Roohi Katyall writes about how to approach the patient with epilepsy, which is still, I think, the seminal way to start to think about these patients. But we need to ask issues pertaining to people with epilepsy of childbearing potential; screen for mood, other comorbidities. Mark Keezer does a great job talking about these. And then as we discussed, Christine Baca, PCU, talks about how to then incorporate those practical considerations into practice. Each author also, I think, emphasizes the need to utilize technology and testing and evaluation to make sure that our care is personalized for our patient. For example, we have a focus on certain special populations. Some patients who we see from the diagnosis of epilepsy end up not having seizures. They may have nonepileptic events. And so, Adriana Bermeo-Ovalle and her co-author talk about how to address those patients. Well, Meriem Bensalem-Owen talks about gender based issues in epilepsy as well. And, and that particular article also was updated and refreshed to really address gender and sex-based issues beyond treating the woman with epilepsy. So, I think in summary, each of them really helps us make sure that we're personalizing the care for patients by emphasizing a very thorough and individualized approach to each of our patients that we see with seizures. Dr Jones: Now that you put it that way, that really did come across as a consistent theme essentially in every article, right? All the way from the evaluation of the patient suspected of having epilepsy to the treatment options to the context of care. Personalization is really kind of a continuous thread throughout the issue. So, I think that's a great one. Dr Hopp: I think it's still aspirational in some sense, but hopefully practical in another. For example, we certainly are going to make a medication selection when we see each individual patient based on their comorbidities, perhaps genetic considerations, and how they may respond to medications or have risks of rash. But there are certainly still guidelines that we need to approach and think about when thinking about populations of people who have epilepsy as a whole. I think that what's interesting in the field of epilepsy is that we still don't have as much consensus as I think we could on the best way to treat, for example, a drug-resistant patient with epilepsy. One of, I think, the biggest areas of opportunity in terms of personalized medicine as we move forward is that there's such variability on patient care based on the epilepsy center, the tools that we have on how to treat these patients. And I think an aspiration is for us to, in the future, be able to see a patient who has seizures or a person who has seizures, maybe put an FDA-approved device, as Dan Friedman talks about in his article, to help detect the seizures. Use AI with EEG to detect abnormalities in their studies. And then use imaging processing and genetic or metabolic markers to really end up stratifying the risk and creating a treatment plan much akin to what's done in the world of cancer care. I think what's so exciting in epilepsy is that we have made so many advances in terms of our treatments, but I think there's so much to do to really stratify and personalize care for our patients that we really could take a lot of lessons from the world of cancer and in other fields of medicine to really be able to apply to our area of specialization. Dr Jones: And I guess that's one of the common tensions in neurology---and medicine, really---is the pull between standardizing and protocolizing. And usually we do better when we're standardized in our care versus that personalization, doing the right thing for that individual person. And I guess expertise lies in the middle, which is why we want people to read these articles, right? Dr Hopp: Exactly. I think you've hit the nail on the head, and I think the takeaway here is really that we need to do both. There's no question that we can't reinvent the wheel for every person who we see in the office who has epilepsy and not apply the knowledge that we've gained based on all of the research and work that's been done in the field of epilepsy. So, for example, we know that if someone is almost 25 years old, Quantum Brody published that shows that if someone does not respond to a few drugs, anti-seizure medicines, the likelihood that they're not going to respond, it is quite high. So, we need to apply data that we have to patients as a whole. But then, I think, what has changed and evolved over the past twenty-five years is our ability to potentially personalize some of that decision making. And that's where I think the field of epilepsy is right now, and hopefully where it's going to go in the next decade or so. Dr Jones: So, what do you think the next big thing in epilepsy diagnosis or management will be? Dr Hopp: I think that technology is really going to play a role. Technology, I think, will take many forms. We hear a little bit about some of the new advances in technology in several articles in this issue. One, for example, is in the ability to manage even emergent seizures or clusters of seizures in patients. The ability to provide a nasal spray that works very quickly is so different than the tools that we had to treat seizures even 10 years ago. I think that technology will likely thread through many different areas of epilepsy care, whether it's in the treatment and availability of different medications or in the ascertainment of epilepsy itself. I think that one of the very exciting areas in technology is in pharmacogenomics and genetics, which hopefully will allow us to close the gap in selecting one of the better medications or best medication for a patient earlier in their diagnosis and in their treatment plan. If we are able to get patients treated more quickly, whether it's with medication or in selection of the best surgical treatment, hopefully we will close the gap in reducing the possibility of drug resistant epilepsy, but also have impact in quality of life and getting patients and people with epilepsy and doing that, doing the things that they want to do such as driving, going to work, getting engaged in the things that make them happy. And so, I think our ability to use technology, whether it's in using a watch to make a diagnosis of seizures or pharmacogenomics to make a good medication selection, hopefully this will allow us to speed up our algorithm in making a diagnosis and getting an effective treatment plan for patients earlier. And ultimately that's our goal. Our goal for patients is ideally to have no seizures and no side effects with a good quality of life. Dr Jones: Yeah, the technology has really been breathtaking. You know, one of the commonalities between your practice and my practice is electrophysiology. I do neuromuscular electrophysiology, which is much simpler than what you do with cerebral electrophysiology. And whenever I sit down next to a colleague who is about to review forty-eight hours’ worth of EEG recordings, I always think what a massive amount of data and I always feel sympathy for them. What, about AI? What about automated processing tools? Is that something that our listeners should look forward to in the future? Dr Hopp: I think so. And I hope it's a blend. I hope that---and I always actually talk about this with trainees because I love EEG so much and I love translating the principles of physics and neurophysiology when we're sitting in front of an EEG with our trainees. I am excited about AI and technology. I will admit that I hope that it doesn't replace human readers because I do think that there is an importance in threading history and semiology and thoughtfulness in a human way with the interpretation of EEG. However, you're absolutely right that the amount of data is just becoming overwhelming for epileptologists and for EEG-ers to be able to synthesize in a reasonable and feasible amount of time. So, we already are seeing the applicability of the AI to, for example, prescreen large, large amounts of EEG data and try to at least give us tools for the ability to screen EEG in a more efficient way. I think some of the more exciting areas of EEG that are coming are in the background, which is in the network analysis in high-density EEG. There are very, very smart mathematicians that currently I'm collaborating with in utilizing network analysis of EEG that will hopefully allow us to apply these algorithms to EEGs that even look normal to the naked eye, but actually may have signals that help us predict who may or may not have seizures. I agree with you wholeheartedly. I think there's so much to come and our collaboration and integration with engineers and mathematicians, I think, is going to be paramount. Dr Jones: Dr Hopp, what was your path to epilepsy? Dr Hopp: Dr Jones, that is a great question. It was not linear and it really evolved over time, but basically went something like this. I majored in behavioral biology in college, and I was fascinated by the brain and how behavior was controlled by either physiology or anatomy or abnormalities in brain function. And as I moved along in my career and education, I really had a passion for neurology and for behavioral science. But I went to medical school and absolutely loved most of the rotations I did. And in fact, I loved OBGYN so much that I changed my entire career path with the goal of becoming an OBGYN and delivering babies. And I was really torn between two specialties of going into neurology or OB. And I went to a very sage advisor, Greg Kane up at Jefferson. And I said, I really don't know what field to go into. I love aspects of both. I like doing testing. I like making immediate impact. But I also love neurology. And he gave me some of the best advice, I think, that I have ever heard. And I try to share with our trainees all the time. He said, Jenny, I think you'll be successful at either, but which do you like reading about? And I had a relative epiphany at the time, and it was no question that I loved reading about neurology. It was very clear to me that reading about neurology and learning about the brain was just fascinating and led me to do a neurology residency where I was exposed to patients with epilepsy. And it really just continued to pique my interest to read about a field that I felt I could have such an impact. I really could help patients make a diagnosis relatively quickly and have a significant impact, maybe as I would in OBGYN but in a little bit different way. And it really has been, to me, the best choice that I could have made. And on a day-to-day basis, I still love reading about neurology. So, it was some of the best advice that I was given and I try to share that with others. Dr Jones: What a great question for a mentor to ask. And I wonder if he was really thinking, if she likes to read, she probably should be a neurologist to begin with. You like to read, don't we? Dr Hopp: I think so. I think he was spot on. I think he knew the answer before he asked the question. Dr Jones: Dr Hopp, thank you for joining us today. Thank you for such a thorough and fantastic discussion on caring for patients with epilepsy and our recent issue on epilepsy for Continuum. Dr Hopp: My pleasure. Thank you for having me. Dr Jones: Again, we've been speaking with Dr Jennifer Hopp, guest editor of Continuum 's most recent issue on epilepsy. Please check it out. And thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use... /episode/index/show/continuumjournal/id/34883740

Care Partner Burden and Support Services in Dementia With Dr. Angelina J. Polsinelli 01/22/2025

Care Partner Burden and Support Services in Dementia With Dr. Angelina J. Polsinelli Informal care partners are essential to the care of people living with dementia, but they often experience significant burden and receive minimal training, support, and resources. Multicomponent interventions can mitigate burden and other negative consequences of caregiving. In this episode, Gordon Smith, MD, FAAN speaks with Angelina J. Polsinelli, PhD, ABPP-CN, author of the article “Care Partner Burden and Support Services in Dementia” in the Continuum® December 2024 Dementia issue. Dr. Smith is a Continuum® Audio interviewer and professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Polsinelli is an assistant professor of clinical neurology at the Indiana University School of Medicine in Indianapolis, Indiana. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Smith: This is Dr Gordon Smith. Today, I've got the great pleasure of interviewing Dr Angelina Polsinelli about her article on care partner burden and support services in dementia. This article appears in the December 2024 Continuum issue, which is on dementia. Ange, welcome to the podcast. And maybe you can begin by just introducing yourself to our audience? Dr Polsinelli: Yeah. Well, thank you for having me. I'm very excited to be here. I'm Ange Polsinelli. I'm a neuropsychologist at Indiana University School of Medicine, where I work in the Department of Neurology. I also work with the Longitudinal Early Onset Alzheimer's Disease study that's led by Liana Apostolova. And I also do some work with the Outreach, Recruitment and Engagement Core of the Indiana Alzheimer's Disease Research Center. This topic that we're going to talk about today is extremely near and dear to my heart. Dr Smith: Well, thanks for joining me. And of course, IU is a powerhouse for Alzheimer's and basketball, in that order. So, we're really excited to have you. I'd like to get right into it. I'll emphasize, we were chatting a little bit about this, Ange, before we started recording, that your topic today is so important for all of us. And I think, you know, this is a podcast that not only neurologists listen to, but students and, and I think increasingly members of the lay public. And this conversation is going to be very important for neurologists and our neurology learners. But I lost my grandmother to Alzheimer's disease. I lost my uncle just in the last week. So, this touches all of us. So, I'm really excited. And then with that in mind, I wanted to begin with a statistic that- you can correct me if I misunderstood it, but it really blew my mind. And that is across the world, as I understand it, care partners provide one hundred and thirty three billion hours of care for people living with dementia yearly, which is pretty staggering. But what's really amazing is that by 2030 that number is expected to go to one point four trillion hours, which I couldn't grab my mind around it. So, I figured I'd try and determine how many years of person work is that and if my math is right, that's almost a hundred and sixty million person years of worth caring for people with dementia yearly across the world. One, are those numbers right? Did I get it right? And then, assuming so, can you put a human face or experience to these numbers? Dr Polsinelli: Yeah, unfortunately those numbers are correct. And with our increasing aging population across the world, that's why you're getting that, you know, exponential increase in care per hours, compounded by the fact that the majority of the caregiving that happens is not done by doctors, physicians, but it's done by these informal care partners, these family members, these friends, these siblings, children, who are providing these really important services and unfortunately not being trained to do this, doing it largely on their own in a lot of respect. But again, these are people who are loved ones of the person living with dementia. There are a variety of kinships, as I mentioned, siblings, children, spouses, friends; and all sorts of age ranges as well. A large majority of them being spouses, and then the second largest majority being children. So, kind of a sandwich generation of people who are caring for parents with Alzheimer's or dementia and then caring for children as well. Dr Smith: Yeah, I was actually struck by the statistic that a quarter of caregivers or so called sandwich caregivers; in other words, they're taking care of a parent and a child. But listen to what you said. But just to call it out, two-thirds of care partners are women, which is a striking statistic. Dr Polsinelli: Absolutely. Women are not only more likely to have dementia, but they are also more likely to be the care partners of somebody who has dementia. And so, the research shows, too, that if you're a care partner, you're at higher risk of developing dementia yourself. So, there's a lot of risk for women when it comes to dementia, development of dementia, but also that the burden and the majority of care needs that are that are supported by women as well. Dr Smith: Right. And there's a lot to unpack in that observation, and maybe we can come back to that. But I wonder if you might talk to us a little bit about the risk of dementia in women caregivers. That's really striking. Is there any thought regarding mechanism for that? Why is that the case? Is it a shared risk factor? Is it cause and effect? What's the story? Dr Polsinelli: So, there are - this is kind of a dissociable or different - kind of two aspects to this, this question. There's the fact that women are at higher risk for developing dementia in general. I think the researchers feel sort of out about why exactly that is. It's not just that women are at higher risk or more likely to develop dementia because they're living longer than men, but there's probably some hormonal aspects of their higher risk factor for dementia. But then there's the other aspect of it too, is that as caregivers, caregivers are at higher risk of developing dementia. And because caregivers tend to be women, that increases or compounds the risk for women as well. We know with caregiving, particularly with someone who's living with dementia, there's more risk of developing things like depression, high stress, health problems, psychological distress, and all of these things increase somebody 's risk for developing dementia as well. Dr Smith: So, I wonder if you might talk a little more, Ange, about what you mean by burden? I think we have in our mind what that is. But in reading your article, there's a lot of- a lot more to it than may meet the eye. Dr Polsinelli: Yeah, it is a more complicated, I guess, topic or terminology that's gone through several iterations over the course of doing research into burden. But when we think about burden, it's really a kind of a combination of both objective experiences and subjective experiences. And these objective, subjective experiences fall into the categories of physical burden, emotional burden, psychological burden. So, there's a lot of different areas of life in which someone can experience burden. But really, it's a combination of factors of both the objective experience, lived experience, and the person 's perception of that experience or what they're dealing with. I should also mention that it appears to be more of that subjective experience or that perception that people have of their objective experience of stressors or burden. That really does determine the person's response to that, if whether they actually perceive their lived experience as being burdensome. Dr Smith: One of the things I found really interesting was the societal and cultural context surrounding this, that there are different cultural expectations and societal dynamics, both in the nature of the burden care partners may feel and how they're viewed. I wonder if you could talk about that? I think it's something that it would seem all of us need to be attuned to as we're working with our patients and their families. Dr Polsinelli: Yeah, this is a topic we could talk for a very long time on. I will try and- I will try not to kind of provide too much of a, or too lengthy of a response. But what we know now is basically that our models of stress and burden that we have typically used or historically used do not incorporate a lot of factors of cultural identity of social and structural determinants of health factors. And so, what we understand now is that stress and the way that people perceive burden is influenced by so many other factors than just kind of an experience and a perception. Because that perception is influenced by so many factors, including, as you mentioned, cultural factors that include how society's familial expectations for us, cultural expectations for us, as well as what our resources are that are determined by, again, structural and social determinants of health, what our community resources are. They're just a lot of different factors that go into how somebody perceives their ability to cope with, again, this kind of life-altering diagnosis that their loved one has received and them being the person who is caring for them through that. Dr Smith: Your article actually goes through in some detail the types of burdens and what drives the burden. And that changes over time. And so I wonder if maybe you can talk a little bit about what the specific natures of the burden are from the caregiver perspective. I mean, what sort of tasks there are, you know, from the many of us who take care of patients, we still don't know unless we've been in the room or in the home watching this happen. So maybe you can describe that for those of our listeners who maybe haven't lived through this? Dr Polsinelli: Yeah, absolutely. I will say upfront that the caregiving experience is going to be different for every single person. And again, kind of dependent on some of those factors that I mentioned before. So, it's going to look different for most people. It's also going to look different through the dementia journeys. The experiences and the requirements earlier on in dementia are going to be a vastly different than what occurs later on when dementia is in the more late stage, moderate or severe stages of the disease. Those care responsibilities absolutely change over the spectrum of that time as well. We know that early on the stage of disease, primary care partner might be spending forty plus hours a day. So, a full-time- or not a day. I'm sorry, a week. So, a full time job carrying it. But that number increases up to a hundred and fifty or so hours per week once the person is more advanced in their disease. So, I say that because the number of hours, I think, make all, like- putting that into perspective of somebody having a full time, multiple full time jobs, basically providing care, I think is really important. But the responsibilities of the care partner are going to range from everything from just helping the person early on in terms of managing finances or managing them, making sure they’re reminding them to take their medications, scheduling their medical appointments for them, maybe taking over all of the driving to get them to their appointments or to get them to family outings and things like that. They're going to be the ones that's going to be the most responsible for reminding people to do something: to eat, to maybe stay on track for a recipe or something that they are making. So, kind of being the eyes and ears for this person right away, basically right at the beginning, even early stages. And then that progresses over time to the person who is caregiving, who is doing potentially everything for this person. So that means helping them use the restroom when they need to, helping them shower. So, there's a physical component to the caregiving as well as that- sort of what we call instrumental support in terms of organizing medical appointments and things like that. They're just basically doing it all for that person. Dr Smith: So, what about a busy clinician who has half an hour to see a dementia patient follow up? Kind of hard to- in these days, you know, we've got, you know, these new therapies to think about as well. What advice do you have to neurologists and other professionals caring for patients? Dr Polsinelli: Yeah. And I think neurologists, I mean, we all have limited time. And I know neurology in particular is like primary care, has even more constrained time. I think one of the biggest things that neurologists can do is really check in with the care partner. So, take a moment to check in with the care partner who's there with the person with dementia to see how are they doing. You're looking for signs of burden or stress, so things like physical complaints like headaches or stomach ache, mentioning feeling burnt out or overwhelmed, maybe feeling depressed or something like that. There's also some short kind of questionnaires that you could give care partners prior to an appointment that they could fill out. You could kind of get a sense of where is this person at this point and then help connect them potentially to some resources that might be available. And I would refer people to that article that has a list of resources in there that you could just basically print out and give to somebody. Dr Smith: Yeah, I was going to make the same point, Ange. Your article is a treasure trove of information. And you know, I'm certainly, I keep all of these on file, as you might imagine, but I'm keeping it in hand for future use. One of the things you talk about that really hit home for me among many is the idea of self-care, and I think sometimes the best care partners are susceptible to burnout because they they're so dedicated. You made the airplane oxygen mask metaphor, which I love. So maybe you can talk about what airplane oxygen masks have to do with dementia care and what advice you have for us and helping our patient’s care partners take care of themselves? Dr Polsinelli: Yeah, absolutely. Self-care is the number one thing I tell care partners to do. It's also one of the hardest things for care partners to do. Like you mentioned, there is a deep, generally speaking, a deep love and caring for the person with who is living with dementia. And the focus becomes on them. And understandably so, the care partners sort of loses focus on themselves and making sure that they're doing okay. So I oftentimes use this oxygen airplane metaphor for people, which is basically, you know, when you're in an airplane and if there's some kind of pressure change in an airplane, they always tell you, put your oxygen mask on first before you help somebody else because you're not going to be any good to anybody if you're passed out. In the airplanes, the pressure changes, you know. You need to be available. you need to be getting what you need in order to help somebody else. So, I think that metaphor, that analogy really works well in dementia care is you need to be- the care partner needs to be caring for themselves and replenishing themselves in order to be the best care partner they can be for their loved one. Dr Smith: Another challenge that, it strikes me as shared between people living with dementia and their care partner is that of social isolation and loneliness, right? If you're working a hundred and fifty hours a week doing anything, you don't have time to care for yourself or very hard to engage in social connections. And one of the loud messages I think I heard from your article is the power of social connectedness, both in terms of resilience and in many different ways. I wonder if you can talk a little bit about loneliness? And I just reflect that in a postpandemic world, this is probably a bigger issue than it was four years ago or four years and three months ago. Dr Polsinelli: Yeah, absolutely. Loneliness and social isolation was a big problem before, and it's even worse now is when I'm hearing from my patients. What I'm seeing in the literature is this postpandemic time is even more has been even more isolating and more problematic for people, but this social network cannot be, as you said, it cannot be overstated in terms of the importance for people. So that social network is important for not only providing potential instrumental care - so that practically care that care partners can use can lean on other people to come into the home to do things for the person living with dementia so the care partner can go practice self-care or go do those errands that need to be done - but also the emotional support as well that social networks can provide for people. And also, you know, social networks for not just the person, the care partner, but for the person living with dementia as well. We know that social engagement in particular is really good for brain health. I mean, we don't think about it, but social engagement is a very cognitive activity. And so, it helps give the brain a bit of a workout. So that social network is important for a lot of different reasons, and understandably a lot harder to maintain in this sort of postpandemic world as well. Dr Smith: As our time starts to come to- close to a close, we're not done yet, but I think we're probably going to have to start winding up. I wonder if we could pivot to something positive and then talk about the joy in this. And by that, I mean you describe and I think we've witnessed relationships and caring, caregiving situations that, as challenging as they are, provides fulfillment and the connection one has with a loved one or sort of that social aspect. Are there things that- predictive of that kind of positivity, and are there ways that we as professional caregivers for patients and their families can facilitate that? Dr Polsinelli: Yeah, there are. There are a couple of things. So, one of which is basically the quality of relationship between the care partner and the person living with dementia already. So that's the quality of that relationship. The better the quality of that relationship, the more likely it is that the care partner will experience more meaning and fulfillment and joy associated with caregiving, kind of outweighing that burden. But the additional piece of that is the more resources, the more mastery they feel about their caregiving or care partnering abilities, the more competent they feel and their ability to do good by the person, their loved one, the person living with dementia, the more likely they are to find that role fulfilling and meaningful. And I think that's where neurologists and other providers can kind of come in as helping people make sure that they have those resources that they are connecting to places where they can learn skills for giving appropriate care so that they can feel confident in what they're doing. There's the preexisting relationship piece that matters a lot. But I think that there's a lot of modifiability that neurologists have, too, in... /episode/index/show/continuumjournal/id/34155500

Treatment of Alzheimer Disease With Dr. David Geldmacher 01/15/2025

Treatment of Alzheimer Disease With Dr. David Geldmacher Anti-amyloid therapies provide the first FDA-approved option to alter AD pathology, but an understanding of overall utility and value to patients remains in its infancy. In this episode, Teshamae Monteith, MD, FAAN, speaks with David S. Geldmacher, MD, FACP, FANA, author of the article “Treatment of Alzheimer Disease” in the Continuum® December 2024 Dementia issue. Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida. Dr. Geldmacher is a professor and Warren Family Endowed Chair in Neurology and the director of the Division of Cognitive and Behavioral Neurology, Department of Neurology, Marnix E. Heersink School of Medicine at the University of Alabama at Birmingham in Birmingham, Alabama. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Host: Transcript Full interview transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Monteith: This is Dr Teshamae Monteith. Today, I'm interviewing Dr David Geldmacher about his article on treatment of Alzheimer's disease, which appears in the December 2024 Continuum issue on dementia. Welcome to our podcast, Dr Geldmacher. How are you? Dr Geldmacher: I’m very well, thank you. It's a pleasure to be here. Dr Monteith: Yeah. So, why don't you introduce yourself to our audience? Dr Geldmacher: Sure. I'm David Geldmacher. I'm a professor of neurology at the University of Alabama in Birmingham and I lead the division of Cognitive and Behavioral Neurology. Dr Monteith: So, I'm really excited about this, to personally learn, and I know that or neurology community is also really excited about this interview. So, why don't we start off with your main objective. Dr Geldmacher: So, my main goal in the article was to review the FDA-approved pharmacologic treatments for dementia. There's lots of ways of thinking about treatment of dementia; psychosocial, caregiver support, and so forth. But I really wanted to focus on the issues of drug treatment because that's what has been our backbone for a long time and now has recently expanded. Dr Monteith: Why don't we talk a little bit about, first of all, the boom in the field? What's that been like? Dr Geldmacher: So, the big change in the field is over the last several years, we've had treatments become available that actually attack the underlying Alzheimer pathology, and that's new and different. For decades, we've been able to treat the symptoms of the disease, but this is the first time we've really been able to get to the root of the pathology and look toward removing amyloid plaques from the brain. Dr Monteith: Let's step back a little bit and talk about the framework of diagnosis and how that leads into the therapeutic potential. I know you're going to dive into some of the biologics, but we should probably talk about the kind of holistic approach to considering the diagnosis. Dr Geldmacher: Sure. So, you know, when someone comes to the clinic with memory complaints, our question we have to ask is, is this neurologic origin, a structural origin like Alzheimer's disease or vascular dementia? Are there complicating factors, the software issues of mood disorders and sleep disorders and pain that can all magnify those symptoms? The clinical reasoning is a critical part of that, but in Alzheimer's disease, typically the problems revolve around difficulty forming new memories of events and activities, the episodic memory. And then it's often accompanied by changes in word finding and semantic knowledge. And those are the things that we look for in the clinic to really point toward an AD diagnosis. And then we support it with exclusion of other causes through blood work and identification of patterns of brain atrophy on MRI. And then most recently in the last couple of years, we've been able to add to that molecular imaging for amyloid with PET scans as well as, most recently, blood-based biomarkers for Alzheimer's pathology. So, it's really been a revolution in the diagnosis over these last several years. Dr Monteith: And when approaching patients or populations of individuals, there seems to be a real full spectrum with looking at the societal burden, the biological impact, of course, risk factors of primary prevention, and now this whole area of brain health and secondary prevention. How do you kind of tie all of this together when talking to patients and family members? Dr Geldmacher: Sure. So, the approaches for brain health apply to everyone. In basically every clinic visited, our brain aging and memory clinic, we reviewed lifestyle approaches to brain health like regular physical exercise, healthy diet, cognitive and social stimulation. And those are fundamental to the approach to everyone, whether they have cognitive impairments that are measurable or not. These are all things that are good for our brain health. And then, you know, focusing on the vascular risk factors in particular and working with the patient and their primary care team to ensure that lipids and blood sugar and blood pressure are all in good healthy ranges and being appropriately treated. Dr Monteith: You know, there's this kind of whole considerations of clinically meaningful endpoints and clinical trials, and even when we're talking to our patients. What would you say the field has kind of identified has the best endpoints in helping patients? Would you call it impaired daily function? Is that like the best hard endpoint? Obviously, there are other things such as caregiver burden, but you know, how do you approach assessing patients? Dr Geldmacher: Defining the endpoints is very difficult. Typically, if we talk to patients and their families, they would like to have better memory or improve memory. How that applies in everyday life actually is daily function. And so, we focus very much on daily function. And when I talk about our therapies, whether they're symptomatic therapies or the new disease-modifying therapies, I really talk about maintenance of function and delays and decline or slowing of decline, helping to foster the person's independence in the activities that they have and be able to sustain that over the longer term. Dr Monteith: And when thinking about diagnosis- and we're going to get into treatments, but when thinking about the diagnosis, and of course, it's full-spectrum from mild cognitive impairment to moderate and severe forms of dementia, but who should have CSF testing and PET imaging? Obviously, these are invasive, somewhat invasive and expensive tests. Should all people that walk in the door that have memory complaints? How do you stratify who should have tests? Dr Geldmacher: I think about this in a big funnel, basically, and the starting point of the funnel, of course, is the person with memory complaints. Then there's that neurologic reasoning. Are these memory complaints consistent with what we expect from the anatomy of Alzheimer's disease, with atrophy in in the hippocampus and temporal lobe? Do they have episodic memory loss or not? That first step is really trying to characterize, do the clinical patterns act like those of Alzheimer's disease or not? And then we follow the Academy of Neurology guidelines, looking for reversible sources of cognitive decline, things like B12 deficiency and depression, sleep disorders and the like, and try to exclude those. We start with structural imaging with everyone, and MRI, typically, that will help us understand vascular burden and patterns of atrophy, looking for things like mesial temporal atrophy or precuneus atrophy that are characteristic of Alzheimer's disease. If those things are all pointing in the direction of AD as opposed to something else, then typically before moving on to CSF or PET scan, we will use blood-based biomarkers, which are one of the big changes in the field in the last year or so, and there are now multiple panels of these available. The downside is they are typically not covered by insurance. On the other hand, they can really help us identify who is likely to have a positive PET scan or positive findings on CSF. We start to provide that counseling and information to the patient before they get to those more definitive tests. We can push people in the other direction. We can say, your blood-based biomarkers are negative or do not indicate AD as the most likely source of your condition now, so let's treat other things. Let's see what else we can focus on. The blood-based biomarkers are now, in our clinic at least, the critical choke point between the routine workout that we've always done on everyone and then the more advanced workup of proving amyloid pathology with CSF or a PET scan. Dr Monteith: How sensitive are those blood biomarkers and how early are they positive? Dr Geldmacher: The sensitivity is generally pretty good, in the ninety plus percent range on average and it depends on which panel. And as you point out, when in the course of symptoms that they're done, we know that they become positive and presymptomatic or asymptomatic people. We're using these kinds of markers to screen people for prevention trials. So, I think when someone is symptomatic, they're a good indicator of the presence or absence of AD pathology. Now that doesn't mean the AD pathology is the sole cause of their symptoms. And so, we still need to think about those other things like sleep and mood and so forth. But they do point us in the in the direction of Alzheimer's change. Dr Monteith: So why don't we talk about some of the more standard older treatments, and it's also important to leave with kind of some rational approach to when we start and what should we be counseling our patients on. So why don't we start with the older, you know, choline esterase inhibitors and then some of the MDA- I guess there's only one modulator, SEPTA modulator. Dr Geldmacher: So, I've been really fortunate in my career span, the time from the first of those symptomatic agents reaching the market in 1993 to seeing the disease modifying drugs enter the market now. I think most neurologists actually have entered practice after those clinical trials of the colon esterase inhibitors were published. So, one of my goals in this article was to review that primary data and what can we expect from those symptomatic drugs. We know that they are inconsistently effective in mild cognitive impairment, and the Academy of Neurology guidelines says there is not strong evidence to use them in mild cognitive impairment. But in mild AD and beyond, the cholinesterase inhibitors provide meaningful benefits. They delay decline, they can delay nursing home placement. They reduce overall costs of care. So, I think they provide real value. So, in the article I have reviewed what the data looked like on those. My approach is to start with oral Donepezil at five milligrams and increase it to ten in everyone who tolerates the five. If for whatever reason the oral Donepezil is not well tolerated, I'll switch to transdermal rivastigmine to help improve tolerability. There are very few head to head comparisons, but nothing suggests that one of the cholinesterase inhibitors is superior to the other for clinical outcomes, and there's no evidence to support conjoint use of more than one at a time. Should someone be showing decline then on typical cholinesterase inhibitor therapy - and people will, it's often delayed, but the decline will reemerge - then I will add the NMDA receptor, a modulator memantine and titrate that up to full dosing, either 10 mg twice a day for the conventional release or 22 mg extended release. And at that point we're sort of on maximal pharmacologic therapy for Alzheimer's disease. These agents can provide some benefit in other conditions, they're off-label except for Lewy body disease where rivastigmine is labeled. But they can provide benefit across different conditions. And there's some preliminary data, for instance, of acetylcholinesterase inhibitors being helpful in vascular cognitive impairment. So, I will use them, but I expect the greatest response when someone really does follow the patterns of Alzheimer's disease. Dr Monteith: And you have a great chart, by the way, and nice figures looking at some of the meta-analyses on cognitive outcomes as well as functional outcomes. So, thank you for that. Dr Geldmacher: In general, all of those tables favor treatment over placebo in the domains of cognition, daily function, neuropsychiatric symptoms. And it's that consistency of result that lets me know that we really are seeing a drug effect, that it's not a class effect with those, that we really are helping our patients. It's not like some studies are positive and some are negative. They are very consistently positive. Small magnitude, but consistently positive. Dr Monteith: And I know we have a lot of patients coming in where, at least, their caregivers are complaining about agitation, and sleep is also a problem for others. And so how do you help that patient? I know you have a good algorithm that also you included in your article, but why don't you summarize how we should approach these symptoms? Dr Geldmacher: Sure. So, for nonpsychotic agitation, you know, just restlessness, wandering, pacing and so forth, my first choice is an off-label use of citalopram. And there is good clinical trials evidence to support that. if someone has psychotic agitation that is with delusions or hallucinations and so forth, I think we do need to move to the antipsychotic drugs. And the one drug that is now approved for treatment of agitation and Alzheimer's disease does fall into that antipsychotic category, along with its various black box warnings - and that's brexpiprazole. For many of our patients, getting coverage for that agent is difficult. It's not on many formularies. So, it is something I progress toward rather than start with. Similarly, for sleep, there is one approved agent for sleep, that's a dual orexin agonist. And it shows effectiveness, but can have some negative cognitive effects, and so I tend not to start with that either. My first choice when sleep is the primary issue for our patients with dementia is trazodone, and there are some small, limited studies for it's off-label used to enhance sleep. It’s safe, inexpensive, often effective, and therefore it's my first choice. Dr Monteith: So, now let's get into the big conversations that everyone is having. Let's talk about the newer disease modifying anti amyloid therapies. Give us a summary dating back 2021 probably, although we can hold the preclinical work, but let's talk about what is available to our patients. Dr Geldmacher: Sure. And the development of anti-amyloid therapies goes all the way back to 1999. So, it's a pretty long course to get us to where we are today. Dr Monteith: Yeah, that's why we limited that. Dr Geldmacher: With that first approved agent with aducanumab in 2021, it received a limited or accelerated approval in FDA parlance. These agents, the aducanumab, lecanemab and donanemab, all approved, are known to remove amyloid pathology from the brain as measured by CSF and/or BIPET. They are amyloid lowering therapies, often called disease-modifying therapies. And across the agents there's some variable results. But if we look at the two with full approval, lecanemab and donanemab, they slow clinical progression by 25% to 35% on average. And that's measured by either cognitive measures or global measures or composite measures, but it's pretty consistent in that range of about one-third slowing. That makes it really difficult to discern in an individual patient, though, because there's so much variability in the progression of the disease already that it can be difficult to tell in one person that these drugs are working. They're also complex to use, so there's a qualification process that involves MRI to exclude things like a high tendency toward hemorrhage. It includes genetic testing for papal E4 status to help us understand the risk for complication, and then once-monthly or twice-monthly infusions with standardized schedule for MRI scanning. So, there's a lot that goes into managing these agents. And they are expensive, and we don't yet know their cost effectiveness. The cost effectiveness of the cholinesterase inhibitors was questioned when they first came out back in the 1990s, and it took five or ten years to really understand that they provided benefit to society and to individuals in those domains of quality of life and return on investment. And we're still learning about that with the disease modifying therapies. Dr Monteith: So, two questions. One, the case that you presented was an individual having symptoms and kind of voiced their desire to be on these therapies. So, people are going to be asking, coming to clinic asking and then of course, they're going to be people that you select out. So, how do you make that decision to recommend this treatment for patients given the potential risk? Dr Geldmacher: We've got some really good guidance from appropriate use recommendation papers for aducanumab and lecanemab, and I'm expecting one from donanemab fairly soon. But the key is to identify individualized risks, and that involves knowing their APOE4 status, knowing their- whether they've had microhemorrhages in the brain previously, and then documenting that they really do have amyloid pathology with something like PET scan to establish those baselines. I talk to people about the burden of twice-monthly infusions or, now with donanemab, once-monthly infusions. And for instance, for someone who's got a working caregiver, getting to an infusion center twice a month can be a significant burden. And then if there are complications, frequent MRI scans and so forth. So, we talk about the burden of entering into this therapeutic pathway. The reality is that people who are qualified generally want it. I have relatively few folks who have said, no, these risks are more than I'm willing to accept. For decades my patients have said, anything you can do to slow this down, I'm willing to try. And now we're seeing that translated to reality with people willing to accept high-risk, high-cost treatments with the chance of slowing their individual progression. Dr Monteith: And how do you select between the two treatments? Dr Geldmacher: So far that's been easy because donanemab's not readily available. Dr Monteith: Outside of clinical trials, right? Dr Geldmacher: Exactly. For prescription use, it's coming in - the first cases have now been infused - but it's not generally available. Nonetheless, what I will do for patients in this is look at the risk tables. So donanemab appears to have in general some higher rates of the Aria complications, amyloid-related imaging anomalies, and some people are going to be more risk tolerant of that for the payoff of potentially faster response. The donanemab trials restructured that. They did their first assessment of... /episode/index/show/continuumjournal/id/34141236

Genetics and Neuropathology of Neurodegenerative Dementias With Dr. Sonja Scholz 01/08/2025

Genetics and Neuropathology of Neurodegenerative Dementias With Dr. Sonja Scholz Recent progress in neurogenetics and molecular pathology has improved our understanding of the complex pathogenetic changes associated with neurodegenerative dementias. In this episode, Katie Grouse, MD, FAAN, speaks with Sonja W. Scholz, MD, PhD, FAAN, an author of the article “Genetics and Neuropathology of Neurodegenerative Dementias,” in the Continuum® December 2024 Dementia issue. Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California. Dr. Scholz is a senior investigator at the National Institutes of Health in Bethesda, Maryland and an adjunct professor of neurology at Johns Hopkins University in Baltimore, Maryland. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Full episode transcript available here: Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Grouse: This is Dr Katie Grouse. Today I'm interviewing Dr Sonia Scholz about her article on genetics and neuropathy of neurodegenerative dementias, which appears in the December 2024 Continuum issue on dementia. Welcome to the podcast, and please introduce yourself to our audience. Dr Scholz: Thank you so much for inviting me. My name is Sonia Scholz. I'm a neurologist working at the National Institutes of Health. My main focus of research and clinical work are neurodegenerative diseases, and I have a particular interest in using modern genomic tools to understand these diseases and potentially leverage it for new translational applications. Dr Grouse: Sonia, we're really excited to have you today and thanks for joining us. Dr Scholz: I'm pleased to be here. Dr Grouse: I'd like to start by asking what you think is the most important message or takeaway point from your article? Dr Scholz: So, this is an article that really captures a very broad and exciting field. So, one thing I wanted to really highlight is that there's a lot of heterogeneity, clinical, pathological, molecular heterogeneity in age-related neurodegenerative dementia syndromes. Our article was really aimed at providing a bird's eye view of the pertinent pathological characteristics, but also important genetic advances and insights and how we can leverage that, particularly in the new physician medicine era, hopefully come up with better treatments and better ways to counsel our patients. Dr Grouse: What do you think is the most challenging aspect of understanding the genetics and neuropathologic basis of neurodegenerative dementias? Dr. Scholz: That's a good question. There’re many big and challenging questions, but I think one of the things we struggle the most with is really the heterogeneity. I see patients with one and the same Mendelian form of dementia. One patient is in their forties another patient is in their eighties, and the clinical manifestations can be very different from one patient to another. There's a lot of heterogeneity, also, on the pathological level. Not every patient has exactly the same distribution. And so, we're starting to slowly define what the underlying causes are, but it's still quite baffling and quite challenging to put them together and understand them. Dr Grouse: Do you feel that the genome-wide association studies has helped our understanding of these diseases, specifically the heterogeneity? And if so how? Dr Scholz: That's a great question, but you're talking to a geneticist here. And I definitely would say genome-wide association studies have helped us a lot in identifying what the underlying disease pathways are and what the relationships between neurodegenerative disease entities are. It really also gave us a better understanding of apparently sporadic diseases where genetic factors are still playing a role. And we can leverage that type of knowledge increasingly to highlight high-risk groups, but also, we can increasingly use it to stratify patients for clinical trials, for example. And that's really exciting and there's still a lot of knowledge that we have to garner very quickly, especially in the non-Alzheimer dementia space. Dr Grouse: You've mentioned, of course, the heterogeneity and these syndromes. And in your article, you go into a lot of the issue of the significant crossover between the genetic links and the neuropathological findings for the various types of neurodegenerative dementias. Do you think that this crossover has been more of a help or a hindrance in better understanding these diseases? Dr Scholz: Yeah, it can be a little bit, you know, challenging to wrap one 's mind around it. But by and large, I think it’s actually good news because it highlights that there is a shared biology between many of the neurodegenerative disease entities. And by figuring out which the pathways are that are very often involved, we can prioritize certain targets for therapy development. But we can also be smarter about how we developed treatments. We could repurpose a drug that has been developed for Alzheimer's disease very easily for Lewy body dementia because we increasingly understand the overlap. And we can also leverage new clinical trials design, like basket trials. This is something that has been really transformative in the oncology sphere and now, increasingly, neurodegeneration. We're trying to apply that kind of thinking as well to our patient populations. Dr Grouse: What do you think our listeners will find to be most surprising when they read the article? Dr Scholz: We often present these diseases in our textbooks as these black-and-white entities, but the reality is that there's a lot of overlap. And we also see that co-pathologies are actually the norm and not the exception, and a lot of the molecular risk factors are shared. It's not really surprising. And I think that overlap and crosstalk between the various diseases is something that's a little bit strange to think about, but it actually makes increasingly sense now that we see the genetic risk profiles coming up. Dr Grouse: In reading your article, I was really struck by how many, or how much the prior studies have been lacking in inclusion of different ethno-racial backgrounds in the patients who've been studied. How can this be improved going forward? Dr Scholz: Yeah, thank you. That's a really important and crucial question, and I think it really takes the collective effort of everybody in the healthcare research community to improve upon that. We need to talk to our patients about genetic testing, about brain donation programs, about referrals to clinical trials, and don't feel shy about reaching out to our colleagues and academic centers, even if you don't have the resources in a smaller institution. We also not only need to engage with the communities, we also need to build up a healthcare research community that has representatives from these various communities. So, it's really a collective effort that we build up and are proactive about building a more equitable healthcare system and research system that works for all of us and that really is going to provide us with the precision medicines that work for everybody. Dr Grouse: What do you think is the biggest debate or controversy related to the genetics and neuropathology of neurodegenerative dementias? Dr Scholz: Yeah, there are loads of interesting debates, but I think in my field, in particular in the genetics is what to do with risk variance. What is it that I actually communicate to the patient? Obviously, I can learn a lot on the bench and I think I can use a lot of the genetic risk factors for molecular modeling, etc. But to which extent should I share that information? Because genetic information is something that we cannot alter and many of the risk factors are actually mild, that they may never result in disease. And so, communicating risk with patients is something that's very challenging and we used to just steer away from it. But now the discussion is starting to shift a little bit. You know, nowadays we are starting to offer, for example, testing for the APOE4 allele in individuals who are considering antiamyloid therapies. And this really, this is precision medicine in his earliest days because it allows us to stratify patients into those that are high-risk versus low-risk and those that need more frequent follow-up or may be advised not to pursue this treatment. And we're probably going to see more of those discussions and the ethics around it. And it's even harder in an aged population where you know, you may never manifest any of the symptoms despite carrying a lot of these risk deals. Dr Grouse: You mentioned, you know, that testing, APOE4 testing for certain populations when deciding to do the antiamyloid immunotherapies. Apart from that, which I think is a really good example of where genetic testing makes sense, what other scenarios do you think it makes sense at this point in time to recommend genetic testing for symptomatic patients who are concerned about neurodegenerative dementias? Dr Scholz: Yeah. So, I usually have a very frank discussion with patients in whom I suspect the genetic etiology. So those are individuals who have a strong family history, individuals from very early onset of the disease where genetic testing may allow us to establish a molecular diagnosis, individualize and refine our counseling, and potentially get them into targeted clinical trials that may be suitable for that. Those are always very nuanced discussions, but I usually start with those high-risk individuals. Increasingly patients are, even with the apparently sporadic forms, are asking me about it. And then I have a frank discussions about the pros and cons and offer it to the patients who really would like to pursue it. Dr Grouse: That makes a lot of sense. What about in the case of patients who are asymptomatic but might have high risks because of, well, family members with certain types of neurodegenerative dementias? When would it make sense, if ever, to do genetic testing for them? Dr Scholz: Yeah, that's a that's a tough situation, to be honest. By and large, I would say I would like to understand what the motivation is to learn about the genetic status. If the motivation is something like family planning, future care planning, etc, then it may be a reasonable thing. But I also want to make it very clear upfront that knowing a genetic status, at least aside from APOE status, at least for now, doesn't actually change the clinical management. And I want to make sure patients understand if they are trying to lower their risk, knowing that genetic status is not going to lower their risk. There are other things, brain health habits, that are really important, that patients should double down on: avoiding vascular disease, avoiding traumatic brain injury, excessive alcohol use, etcetera. It's a discussion that really tries to understand the motivations behind the testing. But some patients are very frank and they want to have it. They may want to contribute to the research community, and so in those instances we may offer it, but I also really want to make them understand that knowing a genetic diagnosis may be acceptable to them, but family members who are related to them may not wish to know. And they can really cause a lot of psychological stress that extends beyond the individual. And then that's something to really consider before actually pursuing testing. Dr Grouse: I think that's a really good reminder, especially about how this can even affect people outside of the patient themselves. I think a lot of us don't even think about that. And certainly, our patients may not either. Taking it a step further, thinking about newly available biomarkers, imaging modalities, how should we incorporate the use of these for our patients when we're suspicious of things like Alzheimer's disease or dementia with the Lewy bodies? Dr Scholz: So by and large these biomarkers are used in in the research area, but we can, in a given patient where maybe the clinical presentation is somewhat atypical, we can use it to help with our diagnostic impression. It doesn't get rid of the clinical evaluation, but at least it gives us a little bit more certainty. Here are the you know, the molecular features, the abnormal amyloid tau deposits, for example, that we're there we're detecting supports diagnosis. May also sometimes help in patients where we suspect there could be even the co-pathology going on where we get a mixture of features, where we can counsel the patients and you know, detecting copathologies is something that is certainly challenging. We know that patients who have more pathologies on average are not doing as well as the ones who have relatively pure disease forms. But this is also an area of intense research and as long as it's used judiciously to help with the diagnostic compression, to reduce a diagnostic odyssey, I think there's a lot of potential there to improve the clinical evaluations nowadays. Dr Grouse: It is really exciting to see the options that are opening up as the years go by, which brings me to my next question. There is certainly, as we know, this new category of disease modifying therapies that are available in the form of the anti-amyloid immunotherapies. What else do you think's on the horizon for treatment and prevention, neurodegenerative dementias, going down the road five, ten, fifteen years down the line? Dr Scholz: Yeah, I think we're entering the era of precision medicine already and we're, we're seeing it already with the anti-amyloid therapies. By and large, I think the standard of care is going to be a multidisciplinary individualized treatment plan that incorporates a more holistic view. It incorporates diet, lifestyle factors, symptomatic management, but also disease modification strategies and potentially even multitarget disease modifying strategies. I think there's a lot more work that we have to do, especially in in the non-Alzheimer’s dementia field. But overall, we're becoming much better in refining our diagnostic impression and in treating some of the complications that arise in these very complex diseases. Dr Grouse: I'm curious, with the future of dementia care and diagnosis being more of a precision medicine model, how do you think this will be possible in an aging population with already, I think, probably a limited access to neurologists even in current state? Dr Scholz: Yeah, this is- these are these are very challenging societal questions. Increasingly, you know, we can use modern technologies such as televisits for follow up, but also, you know, remote monitoring devices. We have to educate the next generation, we need more neurologists, we can't do it alone; but we also need to empower primary care doctors who are usually the first go-to person. And perhaps biomarker testing will become much more common even in the primary care setting. I think overall, you know, we can tackle it by educating the community, empowering participants in various clinical trials, and being flexible of embracing certain new technologies. Dr Grouse: Absolutely. I think that makes a lot of sense and hopefully this will be another call to arms to try to get the word out, get more access to neurology and more people interested and like you said, getting our other colleagues involved and being able to manage it as well. Dr Scholz: Yeah. Dr Grouse: I wanted to transition a little bit into learning more about you. How did you become interested in genetics of neurodegenerative dementias? Dr Scholz: Yeah, it's something, it's an interest that has grown gradually. I started out as a neuroscientist in in Austria, where I was fortunate to work with a group that was very strongly involved in Parkinson's disease care. And I was so thrilled to see patients, you know, treated with deep brain stimulation. But yet in the same clinic, I also saw the patients who were not eligible because they had atypical neurodegenerative diseases. And it's the realization that there is such a broad spectrum of diseases that we frankly don't understand very well, that we really need to work with, understand and hopefully develop the treatments with. That's really has resonated with me. And I've since then really built my entire career around it through different countries at the United Kingdom and the United States. And I'm very fortunate to work at the National Institutes of Health, where I can pursue a lot of these research passions and work with interesting patients and colleagues. Dr Grouse: Well, I've learned a lot today, and I'm sure our listeners would agree. Thank you so much for joining us. It's really been a pleasure speaking with you. Dr Scholz: Well, thank you so much for allowing me to contribute. And, you know, I hope the review article conveys a lot of the exciting developments in this really challenging field. But there's loads of hope that we will eventually get to the point to tackle these conditions. Dr Grouse: I encourage all of our listeners to check out Dr Scholz 's article. It is a great overview of these conditions and the genetics and neuropathology underlining them. Again, thank you so much. Dr Scholz: Thank you for having me. Dr Grouse: Again, today I've been interviewing Dr Sonia Scholz, whose article on genetics and neuropathology of neurodegenerative dementias appears in the most recent issue of Continuum on dementia. Be sure to check out Continuum audio episodes from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/AudioCME. Thank you for listening to Continuum Audio. /episode/index/show/continuumjournal/id/34141131

Fluid Biomarkers in Dementia Diagnosis With Dr. Joseph Quinn 01/01/2025

Fluid Biomarkers in Dementia Diagnosis With Dr. Joseph Quinn Blood-based biomarkers for dementia diagnosis are emerging and rapidly evolving. These fluid biomarkers should be used when the results will impact management decisions, including patient and family counseling, symptomatic therapies, and disease-modifying therapies. In this episode, Allison Weathers, MD, FAAN, speaks with Joseph F. Quinn, MD, FAAN, an author of the article “Fluid Biomarkers in Dementia Diagnosis,” in the Continuum® December 2024 Dementia issue. Dr. Weathers is a Continuum® Audio interviewer and associate chief medical information officer at the Cleveland Clinic in Cleveland, Ohio. Dr. Quinn is a professor in the Department of Neurology at Oregon Health & Science University in Portland, Oregon. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Transcript Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Weathers: This is Dr Allison Weathers. Today, I'm interviewing Dr Joseph Quinn, author along with Dr Nora Gray, of Fluid Biomarkers in Dementia Diagnosis from the December 2024 Continuum issue on dementia. Welcome to the podcast and please introduce yourself to our audience. Dr Quinn: Sure. I'm Joe Quinn. I'm a neurologist at the medical school in Oregon, Oregon Health Science University, and I work in neurodegenerative disease, Alzheimer's disease, and Parkinson's disease. Dr Weathers: Certainly some really weighty topics. But again, as I said, today we want to focus on a really fascinating one, the concept of fluid biomarkers in dementia diagnosis. And we'll perhaps get into monitoring of treatment as well. So, this search for reliable biomarkers in the diagnosis of dementia, certainly not a new topic, but you and your co-author Dr Nora Gray did a really fantastic job in the article right from the get-go, laying out the urgency around this now that there are FDA of treatments that depend on pathologic diagnosis. And it feels like they're more and more announced by the day. Even as I was preparing for this interview a few days ago, the FDA approval for donanemab was announced, with the news making every major media outlet. Well, there are several really critical points made by you both in the article. What do you feel is the most important clinical message of your article? What do you want our listeners to walk away with as their one key takeaway? Dr Quinn: I think we still have the best evidence for CSF biomarkers, cerebrospinal fluid biomarkers, really making a diagnosis with some confidence. PET scans are available for visualizing amyloid and Tau now, but they're so expensive and they're not covered. So, the spinal tap information is what most of us around here really rely on when we want to be sure about what's going on. The blood tests are very promising, very exciting, but as you probably know, there's a lot of different opinions about this out there. Some people are sure that it's a done deal and that we now have a blood test for Alzheimer's disease. After I sent the article off, I opened up my issue of Neurology and there was an editorial saying these blood tests will never work. So, there's different ends of the spectrum on this and we tried to strike a balance with that. So they're very promising. I think before the article is due for revision, things are going to be different. But right now, spinal fluid is probably where we have the most confidence. Dr Weathers: I think that's a really solid takeaway to start our discussion with. And then, I think you both did really strike that very delicate balance in what is right now an area where, as I said, you know, things still are changing by the day. I know for our listeners who do subscribe, and I hope that most of them do, Table 9.1, clinically useful CSF biomarkers for the differential diagnosis of dementia, is one that I personally think I will frequently return to. You and Doctor Gray did just a wonderful job organizing these very complex concepts into an easy read and really powerful tool, especially for use at the bedside. Along the lines of knowing which biomarker to use, how frequently routine care are you ordering these tests on your patients? And do you anticipate this changing the media future? Is this another one of those things that by next week, we'll have a different kind of answer in how we use these tests? Dr Quinn: Yeah, as you said in your preliminary comments, the whole picture has been changed by the approval of these antibody therapies for Alzheimer's disease, lecanumab and just last week, donanemab. Prior to the approval of those two medications, I didn't use spinal fluid tests routinely, but I relied on them when I really needed to make a diagnosis with certainty of something really important hung in the balance. If we were trying to rule out some other treatable, more treatable problem. You know, for example, if it was a question of whether somebody primarily had a psychiatric problem or a neurodegenerative disease, this is something that would really allow me to objectify things. And- but that was a minority of people that I would see for dementia evaluation. You know, now that the two therapies are approved, I'm not actively engaged in administering those therapies very frequently but I can see already that the, the patients that I am discussing this with that spinal fluid is where we're probably going to rely for making a diagnosis of the amyloid burden in the in the living patient until PET scans are approved. If amyloid PET scans are- not approved, but covered by insurance, then those will probably replace the spinal fluid. So those tests in that table, A beta 42, tau, p-tau, one of them that's relatively new is this test for aggregated alpha-synuclein. Those I order with some frequency when I'm in those circumstances. Dr Weathers: That's really helpful for our listeners to hear from an expert such as yourself and to think about as they encounter similar patients. Whenever discussing complex topics such as this one, I'm always curious about, what is the most common misconception or pitfall regarding the use of biomarkers for the diagnosis of Alzheimer's and other dementia that you encounter? Dr Quinn: With respect to the blood biomarkers, you know, we were saying a moment ago that there's a lot of evidence available, but the jury is still out to some degree as to how reliable they are. And I think an important message with respect to those blood biomarkers is that they really are confounded by comorbidities. Remember, we're dealing with an elderly population, so comorbidities like hypertension and renal insufficiency and those kinds of things are relatively common and they can really throw off the blood biomarkers in a more dramatic way than cerebrospinal fluid biomarkers. The other fact, and I can't remember how well we cited this in the article, was that the blood biomarkers don't perform as well in underrepresented minorities. And you know, all of us are appropriately paying more attention to that problem in our practice of medicine. And for these blood biomarkers, that's a real issue. And whether the inferior performance in underrepresented groups is due to more comorbidity or just due to genetic differences is unclear at this time. So those are really important cautions. We mentioned the renal insufficiency and, I think, some of the other comorbidities, but it's a reason to really be careful with the blood biomarkers. Dr Weathers: I think a really important point, especially again, kind of going back to what we were talking about at the beginning of our discussion, there's so much excitement around them. There's so much potential. People think we finally have that kind of silver bullet of diagnosis. So, I think really something to keep in mind. What about in the use of their- in monitoring the efficacy of treatments? Dr Quinn: So that's I think a little earlier in its history in terms of what biomarkers would be useful for monitoring. But the donanemab trial really relied on blood biomarkers as outcome measures and really showed some interesting phenomena. One of them was that plasma neurofilament light, which is all the rage now and all over neurology, people are measuring plasma neurofilament light. It's a nonspecific marker of neuronal damage that makes it out into the serum. So, you can measure it in serum and detect CNS damage in the serum. And intuitively, you would think that would be a good measure of efficacy, but in terms of detecting a treatment effect with donanemab, it didn't perform very well. Conversely, GFAP, which is a marker of astrocyte activation, which I would not have predicted was going to be a sensitive marker for treatment efficacy, performed well in at least the donanemab trial. So, I think it's early in the history of using these markers as outcome measures in clinical trials. And I think we're going to continue to learn as each therapy comes along and as these things come to pass. Dr Weathers: Don't make any assumptions yet? Would that be a good way to sum that up? Dr Quinn: I think that's, yes. I think that's very fair that that we have to be careful about these things. Dr Weathers: OK. So, in summary, I think, does it sound like it's fair to say that the pitfall might be to say it's too early to make any assumptions or any conclusions quite yet? Dr Quinn: That's right. And, and I think, you know, we're going to need to monitor these therapies. I think all of us in neurology have become very accustomed to how you do that in multiple sclerosis, right? We've got MRI scans to be used to monitor therapy, maybe NFL is going to be an appropriate assay there as well. But, you know, there we've all had the experience of a chronic disease and seeing how well your therapy is doing, changing therapy if it fails. So, we’re absolutely going to need those things in in Alzheimer's disease and other neurodegenerative diseases, but it's a little early for us to be sure exactly what the right measures are to make those important decisions. Dr Weathers: And a lot more work to be done for sure. As I mentioned, this is a topic of such great interest and I know, you know, certainly most of our listeners are neurologists or people in our world, medical students and trainees. I know I have one regular nonneurologist listener, my father. He really gets a kick out of listening to my interviews. Even though he is a retired sales manager from IBM and most of the time the topics of discussion are pretty different from his usual favorite podcasts. But this one he will be particularly interested in and I'm sure I will get a list of questions about, particularly because my grandfather unfortunately had Alzheimer's disease. So, I'm sure one of his questions will be about the use of these biomarkers in asymptomatic patients. How do you counsel family members of patients when they inquire about the use of biomarkers for that youth case? What is their utility in presymptomatic testing? Dr Quinn: We know from studies like the Alzheimer's disease neuroimaging initiative and other biomarker studies that some of these markers will be sensitive to pathology. Even in asymptomatic people, that pathology appears long before people develop symptoms. Despite that, I don't recommend that asymptomatic people get any of the testing right now because we do not have evidence that early intervention at the completely asymptomatic stage is valuable. And those clinical trials are underway. There are trials underway right now for people who don't even meet the memory deficit required to have a diagnosis of mild cognitive impairment, people who are entirely cognitively intact, but who on one biomarker study or another have evidence of pathology burden. And the interventions are being started early. And in a few years, we'll know the answer to that. Right now, for somebody to find out that they have pathology without any ability to act on it, I think is not valuable. So, I discourage people from pursuing that. Dr Weathers: And that is really important guidance. Thank you. I know you have, as you mentioned, a beginning in a really diverse neurologic background with expertise, as you said, not only in dementia, but also in Parkinson's disease. And you didn't even mention this, but I know expertise in stroke as well, but your research has been primarily in Alzheimer's. What drew you to dementia and to this specific the aspect of it? How did you become an expert in biomarkers? Dr Quinn: Well, I'll start with the dementia part. So, you know, I was always just interested intuitively in trying to understand how, you know, the brain mediates the mind. So as an undergraduate, I got started working in a lab that was working on the cholinergic system in the brain, which was still being sorted out at that time. It is important in Alzheimer's disease, but it was really where the focus was. And that's what got me interested in Alzheimer's disease, which incidentally is what got Alzheimer interested in Alzheimer's disease. You know, he was very interested in trying to find the biological footprints of all these different neurological and psychiatric diseases. And he usually came up empty-handed until he came across the patient with Alzheimer's disease where there were actual footprints in the brain that he thought was pointing towards what was going on. And we're still wondering about that a hundred years later, I guess that's how I got interested in dementia and Alzheimer's disease. I think I have always spent part of my time as a clinician. I think that's what got me interested in biomarkers, that this problem has always been there that, you know, we've got quite, you know, research criteria for making diagnosis and all that sort of thing. But we've really needed some biological evidence to help us firm this up even before the availability of the therapies. And that's what got me interested in- I'm making another point. I thought that computer research biomarkers are going to help point me towards the causes of the disease, and unfortunately that part hasn't entirely panned out. We've got some research in that area on micro-RNA biomarkers that maybe will bear some fruit down the road, but that's been a tougher, tougher nut to crack. Dr Weathers: But it's so incredibly important work. Well, this has been wonderful. I really enjoyed our conversation, and I always like to end on a hopeful note. What developments in the biomarker space are coming on the horizon are you most excited about? Dr Quinn: I'm hoping that these biomarkers that allow us to evaluate disease efficacy, blood biomarkers that don't require extraspinal taps and that sort of thing. I hope that all comes to pass. And I do think that there is a lot of research underway looking at biomarkers in a novel way that I think could help point us to new targets for therapy, things that you and I haven't even thought of yet. Those are the two things. I guess you asked me for one, I gave you two. Dr Weathers: Oh I think very fair. I agree. Both of those would certainly be wonderful and, and I'm excited as well. Well, thank you, Dr Quinn, for taking the time to speak with me this evening. Dr Quinn: A pleasure. Thank you for having me. Thank you for inviting me to do the piece. It was really a great experience. Dr Weathers: Again, today I've been interviewing Dr Joseph Quinn, who's written with Doctor Nora Gray on fluid biomarkers and dementia diagnosis. This article appears in the December 2024 Continuum issue on Dementia. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/AudioCME. Thank you for listening to Continuum Audio. /episode/index/show/continuumjournal/id/34141016

LATE, Hippocampal Sclerosis, and Primary Age-related Tauopathy With Dr. Vijay Ramanan 12/25/2024

LATE, Hippocampal Sclerosis, and Primary Age-related Tauopathy With Dr. Vijay Ramanan Although Alzheimer disease (AD) is the most common neurodegenerative cause of dementia, other etiologies can mimic the typical amnestic-predominant syndrome and medial temporal brain involvement. Neurologists should recognize potential mimics of AD for clinical decision-making and patient counseling. In this episode, Kait Nevel, MD, speaks with Vijay K. Ramanan, MD, PhD, an author of the article “LATE, Hippocampal Sclerosis, and Primary Age-related Tauopathy,” in the Continuum December 2024 Dementia issue. Dr. Nevel is a Continuum® Audio interviewer and a neurologist and neuro-oncologist at Indiana University School of Medicine in Indianapolis, Indiana. Dr. Ramanan is a consultant and assistant professor of neurology in the Division of Behavioral Neurology at Mayo Clinic College of Medicine and Science in Rochester, Minnesota. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the Academy of Neurology: Social Media Host: Guest: Dr Jones: This is Dr Lyle Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum 's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum Journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Nevel: This is Dr Kait Nevel. Today I'm interviewing Dr Vijay Ramanan about his article he wrote with Dr Jonathan Graff-Radford on LATE hippocampal sclerosis and primary age-related tauopathy, which appears in the December 2024 Continuum issue on dementia. Welcome to the podcast. Vijay, can you please introduce yourself to the audience? Dr Ramanan: Thanks so much, Kait. I'm delighted to be here. So, I am a cognitive neurologist and neuroscientist at the Mayo Clinic in Rochester, Minnesota. I have roles in practice, education and research, but amongst those I see patients with cognitive disorders in the clinic. I help direct our Alzheimer's disease treatment clinic and also do research, including clinical trial involvement and some observational research on genetics and biomarkers related to Alzheimer's and similar disorders. Dr Nevel: Great, thanks for that. So, I'd like to start off by talking about why is LATE hippocampal sclerosis, why is this important for the neurologist practicing in clinic to know about these things? Dr Ramanan: That's a great question. So, if we take a step back, we know that degenerative diseases of the brain are really, really common, and they get more and more common as we get older. I think all neurologists, and in fact most clinicians and large swaths of the general public, are well aware of Alzheimer's disease, which is the most common degenerative cause of cognitive impairment in the population. But there are non-Alzheimer’s degenerative diseases which can produce cognitive difficulties as well. And it's important to be aware of those disorders, of their specific presentations and their implications, in part because it's always a healthy thing when we can be as precise and confident about diagnosis and expectation with our patients as possible. I'll look to the analogy of a patient presenting with a myelopathy. As neurologists, we would all find it critical to clarify, is that myelopathy the result of a compressive spondylotic change? The result of an inflammatory disorder, of a neoplastic disorder, of an infectious disorder? It's critical to guide the patient and choose appropriate management options based on the cause of their syndrome. It would potentially harm the patient if you treated an infectious myelopathy with steroids or other immune-suppressant drugs. So, a similar principle holds in cognitive neurology. I accept with humility that we can never be 100% crystal clear certain about things in medicine, just because when you think you got it all figured out there's a curveball. But I want to get as close to that 100% as possible. And recognizing that disorders like LATE or PART can mimic the symptoms, sometimes even the imaging features of Alzheimer's disease. I think it's critical to have heightened awareness of those disorders, how they look, to be able to apply appropriate counseling and management options to patients. I think this becomes particularly critical as we move into an era of disease-specific, and sometimes disease-modifying, therapies, where applying a choice of a treatment option could have significant consequences to a patient if the thing you're treating isn't the thing that the drug is trying to accomplish. So, having awareness and spreading awareness about some of these non-AD causes of cognitive difficulty, I think, is a big mission in the field. Dr Nevel: Yeah, that makes total sense. And kind of leaning into this, you know, trying to differentiate between these different causes of late-life amnestic cognitive impairment. You know, I'll point out to the listeners today to please read your article, but in addition to reading your article, I'd like to note that there's a really nice table in your article, Table 6-1, where you kind of go through the different causes of amnestic cognitive impairment and the different features that better fit with diagnosis X, Y, or Z, because I think it's a really nice table to reference and really easy to look at and reference back to. But on that note, what is your typical approach when you're seeing a patient in clinic, have a new referral for an older patient presenting with a predominantly progressive amnestic-type features? Dr Ramanan: Excellent question. And this is one that I think has relevance not just in a subspecialty memory clinic, but to all the clinicians who help to diagnose and manage cognitive disorders, including in primary care and general neurology and others. One principle that I think it's helpful to keep in our minds is that in cognitive neurology, no one data point takes precedence over all the others. We have a variety of information that we can gather from history, from exam, from imaging, from fluid biomarkers. And really the fun, the challenge, the reward is in piercing together that information. It's almost like being a lawyer and compiling the evidence, having possibilities on your list and raising and lowering those possibilities to get as close to the truth as you can. So, for patients with a cognitive syndrome, I think the first plank is in defining that syndrome. As you mentioned, if I'm seeing someone with a progressive amnestic-predominant syndrome, I first want to make sure, are we talking about the same thing, the patient, the care partner, and I? Can often be helpful to ask them for some examples of what they see, because sometimes what patients may report as memory troubles may in fact reflect cognitive difficult in other parts of our mental functioning. For example, executive functioning or naming of objects. And so helpful to clarify that in the history to get a sense of the intensity and the pace of change over time, and then to pair that with a good general neurologic exam and some type of standardized assessment of their cognitive functioning. At the Mayo Clinic, where partial to the short test of mental status. There are other ways to accomplish that, such as with an MMSE or a MoCA. If I understand that the syndrome is a progressive amnestic disorder, Alzheimer's disease is the most common cause of that presentation in older adults, it deserves to be on my differential diagnosis. But there might be some other features in the story that could raise or lower those mimics on my list. So, in patients who are, say, older than the age of seventy five, disorders like LATE or PART start to rise higher on the likelihood for me, in particular if I know that their clinical course has been more slow brewing, gradually evolving. And again, most degenerative disorders we expect to evolve not over days or weeks, but over many months to many years. But in comparison with Alzheimer's disease, patients with LATE or with PART would be expected to have a little more slow change where maybe year over year they or their care partners really aren't noticing big declines. Their daily function is relatively spare. There might not be as much involvement into other non-memory cognitive domains. So, these are some of the pieces of the story that can help to perhaps isolate those other non-AD disorders on the list as being more likely and then integrating, as a next level, diagnostic testing, which helps you to rule in and rule out or support those different causes. So, for example, with LATE there can be often out of proportion to the clinical picture, out of proportion to what you see on the rest of their imaging or other profiles, very predominant hippocampal and medial temporal volume loss. And so that can be a clue in the right setting that you may not be dealing with Alzheimer's disease or pure Alzheimer's disease, but that this other entity is there. So, in the big picture, I would say being systematic, recognizing that multiple data points being put together helps you get to that confident cause or etiology of the syndrome. And in particular, taking a step back and thinking about big picture factors like age and course to help you order those elements of the differential, whether AD or otherwise. Dr Nevel: Great, thanks. In your article, you talk about different imaging modalities that can be used, as you mentioned, you know, just another piece of the puzzle, if you will, to try and put together what may be going on with the patient, and recognizing that some of these imaging techniques are imaging is special imaging, not available in a lot of places. You know, and maybe other diagnostic type tests that could be helpful in differentiating between these different disorders may not be available, you know, for the general neurologist practicing in the community. So, what do you suggest to the general neurologist maybe practicing somewhere where they don't have access to some of these ancillary tests that could assist with a diagnosis? Dr Ramanan: Critical question. And here I think there's not likely to be one single answer. As with most things, awareness and recognition is a good place to start. So, some of those clues that I mentioned earlier about the clinical course, about the age, the- we're talking about clinical setting there. So, comfort with and understanding that the clinical setting can help you to be more confident about, for example, LATE or PART being present in contrast to AD. That's important information. It deserves to be part of the discussion. It doesn't necessarily need other tests to have value on its own. A second piece is that tests help, in some cases, to rule in and rule out causes for cognitive difficulty. As part of a standard cognitive evaluation, we would all be interested in getting some blood tests to look for thyroid dysfunction or vitamin deficiencies. Some type of structural head imaging to rule out big strokes, tumors, bleeds. Head CT can accomplish some of that perspective. It's ideal if a brain MRI can be obtained, but again, keeping in mind, what's the primary goal of that assessment? It's to assess structure. Occasionally you can get even deeper clues into a syndrome from the MRI. For example, that very profound hippocampal or medial temporal atrophy. So, increasing awareness amongst clinicians throughout our communities to be able to recognize that change and put it in the context of what they see in other brain regions that can be affected by Alzheimer's or related disorders. For example, the parietal regions can be helpful. And recall that MRI can also be helpful in assessing for chronic cerebrovascular disease changes. This is another mimic that shows up in that table that you mentioned. And so multiple purposes can be satisfied by single tests. Now, you're absolutely right that there are additional test modalities that, perhaps in a subspecialty clinic at an academic medical center, we're very used to relying on and finding great value on; for example, glucose PET scans or sometimes fluid biomarkers from the blood or from the spinal fluid. And these are not always as widely available throughout our communities. Part of the challenge for all of us as a field is therefore to take the expertise that we have gathered in more subspecialty settings and tertiary care settings and translate and disseminate that out into our communities where we need to take care of patients. That's part of the challenge. The other challenge is in continued tool and technological development. There's a lot of optimism in our field that the availability of blood-based biomarkers relevant for Alzheimer's disease may play a part in helping to address some of the disparities in resource and access to care. You can imagine that doing a blood test to give you some high-quality information, there are going to be less barriers to doing that in many settings compared to thinking about a lumbar puncture or a PET scan, both in terms of cost to the patient as well as infrastructure to the clinicians and the care team. So I'm optimistic about a lot of those changes. In the meantime, I think there are, through both clinical evaluation and some basic testing including structural head imaging, there are clues that can help navigate these possibilities. Dr Nevel: So, let's say you have your patient in clinic, you've done your evaluation, maybe gotten some ancillary testing, and you highly suspect either LATE or PART. How do you counsel those patients and their families? How do you manage those patients moving forward who you really suspect don't have, you know, some sort of co-pathology? Dr Ramanan: So, it's- I think it's helpful to remember when patients are coming to see us, either they or the people around them have noticed an issue. And very likely it's an issue that's been brewing for a little while. I think it can be very valuable, very helpful for patients to have answers. What's the cause for the issue? Once you have answers, even if sometimes those answers are not the most welcome things or the things that you'd be looking forward to, answers give you an opportunity to grab hold of what's going on, to define a game plan. So, understanding there is a degenerative disease there, it sheds light on why that individual had had memory symptoms over the years. And it gives them a general expectation that over time on an individualized basis, but generally expecting gradually over many months to many years, there may be some worsening in some of those symptoms helps them to plan and helps them to make the adaptations that are a-ok and great to make to just help you to do the things you want to do. As much as I can, I try to put the focus here closer to how we would view things like high blood pressure or high cholesterol. Those are also chronic issues that tend to be more common as we get older, tend to get more troublesome as we get older. The goal is, know what you're dealing with and take the combination of lifestyle modifications, adaptations in your day-to-day and maybe medications to keep them as mild and as slow-changing as possible. With something like LATE, we don't have specific medication therapies to help support cognitive functioning at this time. There's a lot of hope that with additional research we will have those therapies. But even so, I think it's an important moment to emphasize some of those good healthy lifestyle habits. Staying mentally, socially and physically active, getting a good night's sleep, eating a healthy, balanced diet, keeping good control of vascular risk factors, all of that is critical to keeping the brain healthy, keeping the degenerative disease as mild and slow-brewing as possible. And understanding what some of the symptoms to expect could be. So, with LATE the syndrome tends to be very memory-predominant. There may be some trouble with maybe naming of objects or perhaps recall of emotionally salient historical knowledge, world events, but you're not expecting, at least over the short to medium term, huge intervening on other cognitive functioning. And so that can be helpful for patients to understand. So, the hope is once you know what what you're dealing with, you understand that the disease can look different from person to person. Having a general map of what to expect and what you can do to keep it in check, I think, is the goal. Dr Nevel: I agree with you 100% that it really can be helpful even if we can't, quote unquote, fix it, that for people, family, the patient have a name for what they have and kind of have some sort of idea of what to expect in the future. And they may come in thinking that they have Alzheimer's or something like that. And then, so, to get that information that this is going to be a little different, we expect this to go a little bit differently then it would if you had a diagnosis of Alzheimer's, I can see how that would be really helpful for people. Dr Ramanan: I completely agree. And here's another challenge for us in the field when most patients have heard about Alzheimer's disease and many have perhaps even heard of dementia with Lewy bodies or frontotemporal dementia, but may not have heard of things like LATE. And they're not always easy to go online or find books that talk about these things. Having a name for it and being able to pair that with patient-friendly information is really critical. I see our appointments where we're sharing those diagnosis and making initial game plans as an initial foray into that process. Dr Nevel: Yeah, absolutely. What is the greatest inequity or disparity that you see in taking care of patients with progressive amnestic cognitive impairment? Dr Ramanan: Yeah, great question. I think two big things come to mind. The first, you hinted at very well earlier that there are disparities in access to care, access to diagnostic testing, access to specialists and expertise throughout our communities. If we want diagnostics and therapeutics to be broadly applicable, they do need to be broadly available. And that's a big challenge for us as a field to work to address those disparities. There's not going to be one single cause or contributor to those iniquities, but as a field, I'm heartened to see thought and investment into trying to better address those. Another big weakness, and this is not just limited to cognitive neurology, it's a challenge throughout neurology, is that too many of our research studies are lacking in diversity. And that impacts our biological and pathophysiological understanding of these disorders. It also impacts our counseling and management. Again, if we want a new drug treatment to be broadly applicable throughout all of the patients that we take care of, we need to have data which guides how we apply those treatments. And so again, I'm heartened. This is a big challenge. It's a long standing challenge. It will take deep and long standing committed efforts to reverse. But I'm heartened that there are efforts in the field to broaden clinical trial enrollment, broaden observational research enrollment, and again, broaden access to tools and expertise. As a neurologist, I got into this field because I want to help people, use my expertise and my training to help people. These are steps that we can take to make sure that that help is broadly applicable throughout everybody in our communities. Dr Nevel: Yeah, absolutely. So, kind of segueing from you mentioning research and how we can better... /episode/index/show/continuumjournal/id/34139931

Vascular Cognitive Impairment With Dr. Lisa C. Silbert 12/18/2024

Vascular Cognitive Impairment With Dr. Lisa C. Silbert Vascular cognitive impairment is a common and often underrecognized contributor to cognitive impairment in older individuals, with heterogeneous etiologies requiring individualized treatment strategies. In this episode, Katie Grouse, MD, FAAN speaks with Lisa C. Silbert, MD, MCR, FAAN, an author of the article “Vascular Cognitive Impairment,” in the Continuum December 2024 Dementia issue. Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California. Dr. Silbert is is co-director at Oregon Alzheimer's Disease Research Center, a Gibbs Family Endowed professor of neurology, a professor of neurology at Oregon Health & Science University, a staff neurologist, director of Cognitive Care Clinic, and director of the Geriatric Neurology Fellowship Program at Portland Veterans Affairs Health Care System in Portland, Oregon. Additional Resources Read the article: Subscribe to Continuum: Earn CME (available only to AAN members): Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): More about the American Academy of Neurology: Social Media Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum Journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Grouse: This is Dr Katie Grouse. Today I'm interviewing Dr Lisa Silbert about her article on vascular cognitive impairment, which is part of the December 2024 Continuum issue on dementia. Welcome to the podcast and please introduce yourself to our audience. Dr Silbert: Hi Katie. Thanks for having me here today. Like you mentioned, my name is Lisa Silbert. I am a behavioral neurologist at Oregon Health and Science University and my research focus is in the area of vascular contributions to cognitive impairment and dementia. Dr Grouse: It's such a pleasure to have you and I really enjoyed reading your article. Just incredibly relevant, I think, to most practicing general neurologists, and really to any subspecialty. I'd like to start by asking, what do you think is the main takeaway point of your article for our listeners? Dr Silbert: Yeah. I think, you know, the field of vascular cognitive impairment has changed and evolved over the last several decades. And I would say the main take-home message is that vascular cognitive impairment or vascular dementia is no longer a diagnosis that is only considered in someone who's had acute decline following a clinical stroke. That we have to expand our awareness of vascular contributions to cognitive impairment and consider other forms of the disease that can cause a more subacute or slowly progressive form of cognitive impairment. And there are many, many forms of vascular cognitive impairment that present in a more slowly progressive manner. The other thing I would say as a major take-home message is that we know that cerebrovascular disease is a very common copathology with other forms of dementia and that it lowers one 's threshold for manifesting cognitive impairment in the context of multiple pathologies. And so, in this way, vascular cognitive impairment should be considered as a contributing and potentially modifiable factor in any dementia. Dr Grouse: I found that last point just really, really fascinating. And also, you know, the reminder that a combination of pathologies are more common than any one. To your initial point, I'm actually curious, could you kind of outline for us how you approach diagnosing vascular cognitive impairment? Dr Silbert: Yeah. So with everything in neurology, a lot of it comes down to the initial history taking. And so part of the work up always includes a very detailed history of the presentation of cognitive impairment. Any time there is an acute change in cognition, vascular contribution should be considered, particularly if it's in the context of a clinical stroke or some kind of event that might have lowered cerebral blood flow to the brain. And then having said that, I already mentioned there are many forms of vascular cognitive impairment that can mimic neurodegenerative disease in terms of its course. So being more slowly progressive. And so because of that neuroimaging, and in particular MRI, has become an extremely valuable tool in the workup of anyone who presents with cognitive impairment in order to evaluate contributions from cerebral vascular disease. And so, MRI is a really helpful tool when it comes to teasing out what may be contributing to a patient's clinical syndrome, as well as their other comorbid medical issues, including stroke risk factors and other kind of medical conditions that might contribute to reduce cerebral blood flow. Dr Grouse: I'd love to talk a little bit more about that. You know, as is often the case with neurologic disease associated with vascular pathology, the importance of prevention, you know, focusing on prevention of vascular diseases is so important. What are some things that we can make sure to focus on with our patients and, you know, particularly anything new to be aware of in counseling them? Dr Silbert: Yeah, I'm really glad you asked me that question because like I mentioned, you know, cerebral vascular disease is so common, it lowers one's threshold for cognitive impairment in the face of other age-related brain pathologies. And so, it's really important for all of us to focus on preserving our cognitive health, even starting in midlife. And so, there are a number of areas that I counsel my patients on when it comes to preserving cerebral health and maximizing cerebrovascular health. And so, these stem from the American Heart Association's Life's Essential 8 because we know that preserving cardiovascular health is likely going to also preserve cerebral vascular health. And so, some of the things that I'm very commonly discussing with my patients are controlling stroke risk factors such as blood pressure, blood sugars and cholesterol, maintaining a healthy weight, and then also working towards a lifestyle that includes a healthy diet, no smoking, regular exercise. And then new within the last couple years is also the recommendation that people get adequate sleep, which is something that hasn't been focused on previously. Dr Grouse: I was really interested in reading your article to learn about enlarged perivascular spaces and the role as a mediating factor in the interaction between through a vascular dysfunction and development and progression of neurodegenerative pathology. Can you elaborate on this further? Dr Silbert: So, this is an area that's still largely unknown in the field, and it's an area where there's a lot of emerging work being done. The short answer is, we really don't know with great certainty how it directly connects with accumulating Alzheimer's pathology. But there is some evidence to suggest that the perivascular space is involved in the clearance of toxic solutes from the brain, including Alzheimer's disease pathology. And so there's a lot of work looking at how potentially cerebrovascular risk factors might affect the clearance of those toxic solutes through the perivascular space, including pulse pressure changes that might occur with accumulating cerebrovascular disease and other potential contributors. But one thing I can say with more certainty is that the, you know, location of perivascular spaces is thought to help distinguish those who might have cognitive symptoms due to cerebrovascular disease versus due to cerebral amyloid angiopathy. Or I guess I should say location is helpful in terms of recognizing vascular contributions to cognitive impairment that's due to arteriolosclerosis versus that due to cerebral amyloid angiopathy. In so much that… when we see a lot of perivascular spaces in the basal ganglia in the subcortical structures, that is thought to be more associated with arteriolosclerosis and hypertension type related vascular cognitive impairment. Whereas when we see multiple perivascular spaces within the centrum semiovale, that tends to be more associated with cerebral amyloid angiopathy. Dr Grouse: That's so interesting. And on the topic ofcerebral amyloid angiopathy, you did go into this a good deal. And you know, I think I encourage everybody to revisit the article to remind themselves about, you know, the findings that can increase the suspicion of tribal amyloid angiopathy. However, you also talked about transient focal neurologic episodes, which I think is just a great reminder that, you know, these can occur in this setting and definitely not to miss. Tell us more about what to look for with these types of episodes. Dr Silbert: Transit focal neurologic episodes can be very difficult to tease apart from a transient ischemic attack. And these transient focal neurologic episodes due to CAA can present in a number of different ways. And I think the important take home message for that is that in people who have neuroimaging evidence of CAA to inform them that they are at increased risk for having these focal neurologic episodes and that if they do present to a hospital or an emergency department with any kind of neurologic event, that those treating them are aware that they have evidence of CAA on their neuroimaging because the treatment of course is quite different. So, it's someone presenting with ATIA who has transient neurologic symptoms might be considered urgently to get a thrombolytic or, you know, TPA, whereas someone who has known cerebral amyloid angiopathy or suspected CAA, they likely already have microbleeds on their neuroimaging and in those cases thrombolytics and TPA would be contraindicated and not helpful in terms of the etiology of their neurologic symptoms. Dr Grouse: That's a really good point to make. And I think also in your article you mentioned the use of aspirin if you're suspecting ATIA versus a, you know, a transient amyloid related focal neurologic episode. You know, one you would treat with aspirin and the other one you wouldn't. Dr Silbert: That's right. Dr Grouse: Another sort of interesting topic you delved into was cerebral microinfarct and how this can also contribute to vascular impairment. Could you elaborate a little more on that? Dr Silbert: Yeah. So cerebral microinfarcts are kind of the hidden cause of or a hidden cause of vascular cognitive impairment. And it's extremely challenging because by definition they are not visible on routine clinical neuroimaging. It's something that we are more aware of based on pathological studies and neuroimaging studies that have been done at ultra-high field strength like 7T MRI. And so, we are just learning more about how prevalent they are in certain conditions and how we can only look at these after death when we're looking at brain tissue and then go back and realize that these play a significant role in cognitive decline when someone is alive. It's important to understand that we're probably only appreciating kind of the tip of the iceberg when we're evaluating a patient and looking at their neuroimaging. That what we're actually seeing on MRI are only the things that are actually quite relatively big and obvious. And that a lot of these neuroimaging features of vascular cognitive impairment are actually associated with pathologic features that we're missing such as microinfarcts. But the hope is that by treating all individuals, particularly those who already have signs of vascular cognitive impairment, by modulating their stroke risk factors and focusing on maintaining brain health, that those will, interventions will also reduce the incidence of microinfarcts. Dr Grouse: What do you think is the greatest inequity or disparity you see in treating patients with vascular cognitive impairment? Dr Silbert: I think the greatest disparity is- really starts way before I treat a patient. That relates to really focusing on healthy lifestyle factors early in life and being able to, you know, afford fruits and vegetables, and having the advantages of being able to exercise regularly, and just being aware that all of these things are extremely important before older age. So, these are things that, you know, I think more education and awareness and greater access to healthcare will definitely improve access to. Even preventative healthcare is a disparity and not available across all of the population and geographic locations. So, I think of the- all the dementias, vascular cognitive impairment probably has the greatest association with health and social disparities in terms of primary prevention and access to care. Dr Grouse: All really important things to consider. I have to say when, you know, reading your article, dare I say I came away with a little bit of hope thinking, you know, even with, you know, how little we still, you know, or how much we still need to do to really learn how to fight Alzheimer's and, you know, prevent it and, and, you know, help with its progression. The idea that in so many cases, even just doing what we can to prevent the vascular or cognitive impairment can really help any type of dementia. That was really a strong message for me. Do you mind elaborating on that a little more? Dr Silbert: No, not at all. I agree. I really am hopeful about the prevention and treatment of dementias and through the treatment and prevention of cerebrovascular disease. I think that is a true reality, just like, you know, as we were discussing before, the treatment and prevention of cerebrovascular disease really should be a part of the treatment of any type of cognitive impairment and recommendations for prevention of cognitive impairment. This is the, you know, one thing we know is largely modifiable and preventable in most cases. I think the, really the key thing is just education and making sure that people understand that these are things that really need to be, they need to be engaged in in midlife and that it's much harder to reverse these- the damages once you have them in later life. Having said that, I do think that there's greater awareness of maintaining healthy lifestyle and maintaining awareness of stroke risk factors. And I think we're already starting to see a reduction in dementia worldwide in several large population-based studies, and probably that is due to more attention to the modifying stroke risk factors. So, I agree with you, it's very encouraging. Dr Grouse: Is there anything exciting on the horizon that you can tell us about that we should all be keeping our eyes out for? Dr Silbert: Yeah. So, you know, I'm really interested in this connection between vascular cognitive impairment and Alzheimer's disease. And it's a real area of exciting new research. And so I think we're going to have more answers as to how, whether and how, cerebrovascular disease is directly linked to accumulating neurodegenerative disease or neurodegenerative pathologies. The other area that's, I think, really exciting, that's moving forward, is the in the area of blood-based biomarkers for vascular cognitive impairment. As these emerge, we'll be able to really identify those at greatest risk for vascular cognitive impairment, but also identify novel mechanisms that lead to VCI that can be targeted for therapeutic intervention. Dr Grouse: Well, I'm really excited to see what's coming down the pipeline and what more we'll learn in this area. So, thank you so much for everything you've done to contribute to this field. Dr Silbert: Yeah. Dr Grouse: I wanted to ask a little bit more about you. What drew you to this work? Dr Silbert: Well, actually, so my very first published manuscript in medical school was a case report and review on MELAS, which is mitochondrial encephalopathy with lactic acidosis and strokelike syndrome. And so, I was really fortunate to have Dr Jose Biller, who is a renowned expert in stroke and cerebrovascular disorders, as my mentor for that paper. And so, that got me really interested in neuroimaging findings of cerebral vascular disease. And so when I was a fellow at Oregon Health and Science University, I was then really fortunate to be able to work with Jeffrey Kaye's oldest old population. And in working with that population, I really became interested in their neuroimaging findings of these white matter lesions and just realizing how prevalent they were in that population, you know, it just led me to start investigating their clinical significance and etiology, which kind of led me along this path. Dr Grouse: You know, Lisa, thank you so much. I really learned a lot from your article, and I think our listeners will definitely find that it was very helpful for their practice. Thank you so much for joining us. Dr Silbert: Thank you so much, Katie. It's been really fun. Dr Grouse: Again, today I've been interviewing Dr Lisa Silbert, whose article on vascular cognitive impairment appears in the most recent issue of Continuum on dementia. Be sure to check out Continuum audio episodes from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/AudioCME. Thank you for listening to Continuum Audio. /episode/index/show/continuumjournal/id/34139841

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