Podcast appearances and mentions of aaron berkowitz

We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Aye presents a case of behavior change, headaches, and blurry vision to Vale. Neurology DDx Schema Aye Chan Moe Thant (@AyeThant94) Aye graduated from University of Medicine, Mandalay, Myanmar, and has been working with her mentor neurologist, one of only… Read More »Episode 395: Neurology VMR – Behavior change, headaches, and blurry vision

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: Approach to Vision Loss Subscribe to Continuum®: shop.lww.com/Continuum  Earn CME (available only to AAN members): continpub.com/AudioCME  Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com  Social Media facebook.com/continuumcme  @ContinuumAAN  Host: @AaronLBerkowitz  Full episode transcript available here 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 causes of optic neuropathy. Or you could have arteritic versus nonarteritic with the vascular, the arteritic usually being giant cell arteritis. And the way the optic nerve circulation is, you can have an anterior ischemic optic neuropathy or a posterior ischemic optic neuropathy defined by the presence of disc edema suggesting it's anterior, the front of the optic nerve, or not, suggesting that it's retrobulbar or posterior optic nerve. So what category am I- we mentioned toxic, metabolic nutritional. And there are many causes in those categories of optic neuropathy, usually bilateral. You can have degenerative or inherited. And there are causes of inherited optic neuropathies such as Leber hereditary optic neuropathy and dominant optic atrophy. And then there's a group I call the mechanical optic neuropathies. The obvious one is traumatic, and that can happen in any piece of tissue. And then the other two relate to the particular anatomy of the eyeball and the optic nerve, and the fact that the optic nerve is a card-carrying member of the central nervous system. So, it's not really a nerve by the way, it's a tract. Think about it. Anyway, white matter tract. It is covered by the same fluid and meninges that the rest of the brain. So, what mechanically can happen? Well, you could have an elevated intraocular pressure where that nerve inserts. That's called glaucoma, and that would affect the front of the optic nerve. Or you can have elevated intracranial pressure. And if that's transmitted along the optic nerve, it can make the front of the optic nerve swell. And we call that specifically papilledema, optic disk edema due specifically to raised intracranial pressure. We actually even can have low intraocular pressure cause something called hypotony, and that can actually even give an optic neuropathy the swelling of the optic nerve. So, these are the mechanical. And if you were to just take that list and use it for any piece of tissue anywhere, like the heart or the kidney, you can come up with your own mechanical categories for those, like pericarditis or something like that. And then all those other categories would fit. But of course, the specific causes within that pathophysiology are going to be different based on the piece of tissue that you have. In this case, the optic nerve. Dr Berkowitz: In our final moments here, we've talked a lot about the approach to monocular visual loss. I think most neurologists, once we find a visual field defect, we breathe a sigh of relief that we know we're in our home territory here, somewhere in the visual task base that we've studied very well. I'm not trying to distinguish ocular causes amongst themselves or ocular from optic nerve, which can be very challenging at the bedside. But one topic you cover in your article, which I realized I don't really have a great approach to, is transient binocular visual loss. Briefly here, since we're running out of time, what's your approach to transient binocular visual loss?  Dr Newman: We assume with transient binocular vision loss that we are not dealing with a different experience in each eye, because if you have a different experience in each eye, then you're dealing with bilateral eyeball or optic nerve. But if you're having the same experience in the two eyes, it's equal in the two eyes, then you're located. You're located, usually, retro chiasmally, or even chiasm if you have pituitary apoplexy or something. So, all of these things require imaging, and I want to take one minute to talk about that. If you are sure that you have monocular vision loss, please don't get a brain MRI without contrast. It's really useless. Get a orbital MRI with contrast and fat suppression techniques if you really want to look at the optic nerve. Now, let's say you you're convinced that this is chiasmal or retrochiasmal. Well then, we all know we want to get a brain MRI---again, with and without contrast---to look specifically where we could see something. And so, if it's persistent and you have a homonymous hemianopia, it's easy, you know where to look. Be careful though, optic track can fool you. It's such a small little piece, you may miss it on the MRI, especially in someone with MS. So really look hard. There's very few things that are homonymous hemianopias MRI negative. It may just be that you didn't look carefully enough. And as far as the transient binocular vision loss, again, remember, even if it's persistent, it has to be equal vision in the two eyes. If there's inequality, then you have a superimposed anterior visual pathway problem, meaning in front of the chiasm on the side that's worse. The most common cause of transient binocular vision loss would be a form of migraine. The visual aura of migraine usually is a positive phenomenon, but sometimes you can have a homonymous hemianopic persistent defect that then ebbs and flows and goes away. Usually there's buildup, lasts maybe fifteen minutes and then it goes away, not always followed by a headache. Other things to think of would be transient ischemic attack in the vertebra Basler system, either a homonymous hemianopia or cerebral blindness, what we call cortical blindness. It can be any degree of vision loss, complete or any degree, as long as the two eyes are equal. That should last only minutes. It should be maximum at onset. There should be no buildup the way migraine has it. And it should be gone within less than ten minutes, typically. After fifteen, that's really pushing it. And then you could have seizures. Seizures can actually be the aura of a seizure, the actual ictal phenomenon of a seizure, or a postictal, almost like a todd's paralysis after a seizure. These events are typically bright colors and flashing, and they last usually seconds or just a couple of minutes at most. So, you can probably differentiate them. And then there are the more- less common but more interesting things like hyperglycemia, non-ketonic hyperglycemia can give you transient vision loss from cerebral origin, and other less common things like that. Dr Berkowitz: Fantastic. Although we've talked about many pearls of clinical wisdom here with you today, Dr Newman, this is only a fraction of what we can find in your article with Dr Biousse. We focused here on monocular visual loss and a little bit at the end here on binocular visual loss, transient binocular visual loss. But thank you very much for your article, and thank you very much for taking the time to speak with us today. Again, today I've been interviewing Dr Nancy Newman about her article with Dr Valerie Biousse on the approach to visual loss, which appears in the most recent issue of Continuum on neuro-ophthalmology. Be sure to check out Continuum audio episodes from this and other issues. Thank you so much to our listeners for joining us 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 description: We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Sebastian presents a case of confusion to Aye. Aye Chan Moe Thant ( @AyeThant94 ) Aye is a physician from Myanmar and now working as a clinical research team member at the Department of Neurology, Washington University in Saint… Read More »Episode 386: Neurology VMR – Confusion

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: Neuroimaging in Epilepsy Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Guest: @ctskidmore  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 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 you to read the article and look at the images of some of the conditions we've been talking about and some of these findings that can be seen on interictal PET or ictal SPECT to get a sense of the visual aspects of what we've been discussing. So again, today I've been interviewing Dr Christopher Skidmore about his article on neuroimaging 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 so much to our listeners for joining us today.  Dr Skidmore: Thank you for having me. 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 description: We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Aye presents a case of double vision to Vale. Aye Chan Moe Thant ( @AyeThant94 ) Aye is a physician from Myanmar and now working as a clinical research team member at the Department of Neurology, Washington University… Read More »Episode 379: Neurology VMR – Double Vision for One Day

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 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. 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: Classification and Diagnosis of Epilepsy Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Guest: @RoohiKatyal 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 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 helpful in these guidelines. And yet, as I'm sure you experience your practice, as I do in mine, sometimes a little challenging to apply. So, continuing with our made-up hypothetical patient here, let's say at some point in the subsequent years, they have a second unprovoked seizure, still have a normal EEG but they do go on an anti-seizure medicine. And maybe four or five years later, they're seizure-free on a low dose of an anti-seizure medicine. And they say, you know, do I really still need this medicine? I'd really like to come off of it. What do you think? Is that safe? How do you talk about that with the patient? This definition of ten years and five years off medicine seems to be---and maybe unless someone's seeing a lot of children and young adults, a relatively uncommon scenario. It's we've had a first unprovoked seizure. We never figured out why. We don't really know why they had the seizure. We can't really gauge their subsequent risk. They're on medicines, they don't want to be on them and it's only been a few years, let's say three, four, or five years. How do you frame discussion with the patient? Dr Katyal: Yeah, so that's the definition of being resolved. But in terms of tapering off medications, we can usually consider tapering off medications earlier as well, especially if they've been seizure-free for two or more years. Then again, as we mentioned earlier, it would be a very individualized decision and discussion with the patient, that we could consider tapering off of medication. And we would also want to definitely discuss the risk of breakthrough seizures as we taper off and the risks or the lifestyle modifications that would come with it if they have another breakthrough seizure. So, all those things will go into careful concentration when we decide to taper off, because especially driving restriction may be a big, you know, hard stop for a lot of patients that, you know, now is not a time to taper off medication. So, all of these factors will go into consideration and we could consider tapering off earlier as well.  Dr Berkowitz: That's very helpful. Yeah, as you said, when we're tapering off medications, if that's the direction the patient wants to go during that period, obviously we wouldn't want them to drive, or be up on a ladder, or swimming alone. You said that some patients might say, actually, I'll keep the medicine, whereas some might say, OK, I'll hold off on all these activities and hope that I can be off this medication. I remember epilepsy colleagues quoting to me at one point that all comers, when a patient's been seizure-free for two years, they estimate the risk of relapse, of having another seizure, somewhere around thirty to forty percent. In your expert opinion, is that about what you would quote to a patient as well,. about a thirty to forty percent, all comers? Obviously not someone who's had a history of status epilepticus and has a lesion or a syndrome, but in the sort of common situation of some unprovoked seizures in an adult, we don't have a clear ideology. Is that thirty to forty percent figure, more or less, you would place the risk when you talk to the patient? Or?  Dr Katyal: Yeah, absolutely, especially if the neuroimaging is completely normal, all their EE GS have been normal. They have been in this situation---you have a young patient with two seizures separated by so many years. After three or four years of being on the medication and, you know, the patient has been adhering. There are no more seizures. Thirty to forty percent seems reasonable, and this is what I usually tell them that the risk of, as we taper off medications, that risk is not zero but it's low. And around thirty percent is relatively where we would place the risk at. Dr Berkowitz: We've said in this theoretical case that the EEG is normal. But last question, I've heard some practitioners say that, well, let's say the patient did have an abnormal EEG early on. Not a syndrome, but had maybe a few focal spike wave discharges or sharps and that made you convinced that this patient had epilepsy. But still becomes seizure free for several years. I've heard of some practitioners repeating the EEG before tapering the anti-seizure medicines and I always wonder, would it change anything? It's a brief twenty-minute period. They still have one spike, but I tell them they can't come off. If the spikes are gone, it may be because of the medication, and maybe when I take them off they would have a spike. And how do you use---do you use or how do you use EEG in that decision of whether to taper a medicine? Dr Katyal: Yeah. In general, I would not always use an EEG for considering tapering off medication. Again, it's very individualized decision. I can give you a hypothetical example, but it's a fairly common one, is that if an individual with let's say focal seizures with impaired awareness, they live alone, they live by themselves. Oftentimes they'll say that, I'm not sure if I'm missing any seizures because nobody has seen them. I may or may not be losing awareness, but I'm not too certain. They have not had any definite seizures for history in the last couple of years and are now considering tapering off medication. So, this may be a situation where I may repeat an EEG, and perhaps even considering the longer EEG for them to understand their seizure burden before we decide to taper off medication. But in most situations, especially if we consider the hypothetical situation you had mentioned for the young patient who had to witness seizures separated by several years and then several years without any seizures, that may be a good example to consider tapering off medication, especially considering all the tests that had been normal before then.  Dr Berkowitz: That's very helpful to hear. And of course, this is your expert opinion. As you said, no guidelines and different people practice in different ways, but helpful to hear how you approach this common and challenging scenario for practitioners. Well, I want to thank you again, Dr Katyal. This has been a great opportunity to pick your brain on a theoretical case, but one that I think presents a number of scenarios that a lot of us---myself as a general neurologist, as well as you and your colleagues as epileptologists, we all see in general practice patients with unprovoked seizures and a revealing workup, and how to approach this challenging scenario based on the guidelines and on your expert opinion. I learned a lot from your article. Encourage our readers again to take a look. A lot of very helpful tables, figures, and explanations, some of the concepts we've been discussing. So again, today I've been interviewing Dr Roohi Katyal about her article on classification and diagnosis of 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 again so much to our listeners for joining us.  Dr Katyal: Thank you for having me. 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 description: We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Dr. Sebastian Green presents a case of generalized weakness to Aye. Neurology DDx Schema Aye Chan Moe Thant ( @AyeThant94 ) Aye is a physician from Myanmar and now working as a clinical research team member at the… Read More »Episode 372 : Neurology VMR – Generalized Weakness

A pragmatic and organized approach is needed to recognize patients with symptomatic Alzheimer Disease in clinical practice, stage the level of impairment, confirm the clinical diagnosis, and apply this information to advance therapeutic decision making. In this episode, Aaron Berkowitz, MD, PhD, FAAN, speaks with Gregory S. Day, MD, MSc, MSCI, FAAN, author of the article “Diagnosing Alzheimer Disease,” in the Continuum December 2024 Dementia issue. Dr. Berkowitz is a Continuum® Audio interviewer associate chief medical information officer at the Cleveland Clinic in Cleveland, Ohio. Dr. Day is an associate professor in the Department of Neurology at Mayo Clinic Florida in Jacksonville, Florida. Additional Resources Read the article: Diagnosing Alzheimer Disease Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Guest: @GDay_Neuro Full episode transcript available here Dr Jones: This is Doctor 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 have the pleasure of interviewing Dr Gregory Day about his article on Alzheimer disease, which appears in the December 2024 Continuum issue on dementia. Welcome to the podcast, Dr Day. Would you mind introducing yourself to our audience?  Dr Day: Thanks very much, Aaron. I'm Gregg Day. I'm a behavioral neurologist at Mayo Clinic in Jacksonville, Florida, which means that my primary clinical focus is in the assessment of patients presenting typically with memory concerns and dementia in particular. Dr Berkowitz: Fantastic. Well, as we were talking about before the interview, I've heard your voice many times over the Neurology podcast and Continuum podcast. I've always learned a lot from you in this rapidly changing field over the past couple of years, and very excited to have the opportunity to talk to you today and pick your brain a little bit on this very common issue of evaluating patients presenting with memory loss who may have concerns that they have dementia and specifically Alzheimer disease. So, in your article, you provide a comprehensive and practical approach to a patient presenting for evaluation for possible dementia and the question of whether they have Alzheimer disease. The article is really packed with clinical pearls, practical advice. I encourage all of our listeners to read it. In our interview today, I'd like to talk through a theoretical clinical encounter and evaluation so that I and our listeners can learn from your approach to a patient like this. Let's say we have a theoretical patient in their seventies who comes in for evaluation of memory loss and they and/or their family are concerned that this could be Alzheimer disease. How do you approach the history in a patient like that? Dr Day: It's a great way to approach this problem. And if you're reading the article, know that I wrote it really with this question in mind. What would I be doing, what do we typically do, when we're seeing patients coming with new complaints that concern the patient and typically also concern those that know the best? So be that a family member, close friend, adult child. And in your scenario here, this seventy year old individual, we're going to use all the information that we have on hand. First off, really key, if we can, we want to start that visit with someone else in the room. I often say when talking to individuals who come alone that there's a little bit of irony in somebody coming to a memory assessment alone to tell me all the things they forgot. Some patients get the joke, others not so much, but bringing someone with them really enhances the quality of the interview. Very important for us to get reliable information and a collateral source is going to provide that in most scenarios. The other thing that I'm going to start with, I'm going to make sure that I have appropriate time to address this question. We've all had that experience. We're wrapping up a clinical interview, maybe one that's already ran a little bit late and there's that one more thing that's mentioned on the way out the door: I'm really concerned about my memory or I'm concerned about mom 's memory. That's not the opportunity to begin a memory assessment. That's the opportunity to schedule a dedicated visit. So, assuming that we've got someone else in the room with us, we've got our patient of interest, I'm going to approach the history really at the beginning. Seems like an easy thing to say, but so often patients in the room and their caregivers, they've been waiting for this appointment for weeks or months. They want to get it out all out on the table. They're worried we're going to rush them through and not take time to piece it together. And so, they're going to tell you what's going on right now. But the secret to a memory assessment, and particularly getting and arriving at an accurate diagnosis that reflects on and thinks about cause of memory problems, is actually knowing how symptoms began. And so, the usual opening statement for me is going to be: Tell me why you're here, and tell me about the first time or the first symptoms that indicated there was an ongoing problem. And so, going back to the beginning can be very helpful. This article is focused on Alzheimer disease and our clinical approach to the diagnosis of Alzheimer disease. And so, what I'm going to expect in a patient who has a typical presentation of Alzheimer disease is that there may be some disagreement between the patient and the spouse or other partners sitting in the room with me about when symptoms began. If you've got two partners sitting in the room, maybe an adult child and a spouse, there may be disagreement between them. What that tells me is at the onset, those first symptoms, they're hard to pin down. Symptoms typically emerge gradually in patients with symptomatic Alzheimer disease. They may be missed early on, or attributed or contributed to other things going on in the patient's time of life, phase of life. It's okay to let them sort of duke it out a little bit to determine, but really what I'm figuring out here is, are we talking about something that's happened across weeks, months or more likely years? And then I'm going to want to listen to, how did symptoms evolve? What's been the change over time? With Alzheimer disease and most neurodegenerative diseases, we expect gradual onset and gradual progression, things becoming more apparent. And at some point, everyone in the room is going to agree that, well, as of this state, there clearly was a problem. And then we can get into talking about specific symptoms and really begin to pick that apart the way that we traditionally do in any standard neurological assessment. Dr Berkowitz: Fantastic. And so, what are some of the things you're listening for in that history that would clue you in to thinking this patient may indeed be someone who could have Alzheimer's disease and going to require a workup for that diagnosis? Dr Day: It's pretty common when I have new trainees that come to clinic, they just head into the exam room and they sort of try to approach it the way that we would any patient in the emergency department or any other clinical scenario. The challenge with that is that, you know, we're taught to let the patient speak and we're going to let the patient speak - open-ended questions are great - but there's only so many questions you need to sort out if someone has a memory problem. And memory is really only one part, one component, of a thorough cognitive evaluation. And so, I'm going to help by asking specific questions about memory. I'm going to make sure that there is memory challenges there. And whenever possible, I'm going to solicit some examples to back that up, add credibility and sort of structure to the deficits. I'm also going to choose examples that help me to understand how does this concern, or this complaint, how does that actually affect the patient in their day-to-day life? Is it simply something that they're aware of but yet hasn't manifested in a way that their partner knows about? Is it to a level where their partner's actually had to take over their responsibility? It's causing some difficulties, disability even, associated with that. That's going to be important for me as I try to understand that. So, I'll ask questions when it comes to memory, not just, you know, do you forget things, but do you manage your own medications? You remember to take those in the morning? Do you need reminders from your partner? What about appointments; health appointments, social appointments? Are you managing that on your own? Sometimes we need a little bit of imagination here. Partnerships, and particularly those who have been together for a long time, it's natural that different people are going to assume different responsibilities. And so, might have to say, Imagine that you went away for the weekend. Would you worry about your partner remembering to take their medications over that time frame? That can help to really solidify how much of an impact are these challenges having on a day-to-day basis. I may ask questions about events, something that they maybe did a couple of weeks ago. Is the patient likely to remember that event? Are they going to forget details? Maybe the most important of all, with each of these, when there's a yes or an affirmation of a problem, we want to be clear that this represents a change from before. We all have forgetfulness. Happens on a day-to-day basis, and we all pay attention to different details, but what we're concerned about and typically the reasons patients want to come and see us as neurologists is because they've noticed a change. And so, I'm going to focus in on the things that represent a change from before. After I've discussed memory, I think it's really important to talk about the other domains. So, how is judgment affected? Decision-making?  In a practical way, we often see that borne out in financial management, paying the bills. Not just paying them on time and consistently, but making wise choices when it comes to decisions that need to be made. You're out at a restaurant. Can you pay the bill? Can you calculate a tip? Can you do that as quickly and as efficiently as before? Are we starting to see a breakdown in decision-making abilities there? We can sometimes lump in changes in behavior along with judgment as well. The patient that you know, maybe isn't making wise choices, they've picked up the phone and given their social security number out to someone that was calling, seeming to be well-meaning. Or maybe they've made donations to a few more institutions than they would have otherwise? Again, out of- out of order. Again, something that could be atypical for any individual. Looking for behavioral changes along with that as well. And then I'm going to talk about orientation. What's their ability to recognize days of the week, date of the month? Do they get lost? Is there concerns about wayfinding? Thinking about that, which is really a complex integration of some memory, visuospatial processing, judgment, problem solving, as we look to navigate our complex world and find our way from point A to B. And then I like to know, you know, what are they doing outside of the home? What are they doing in the community? How are they maintaining their engagement? Do they go to the store? Do they drive? An important topic that we may need to think about later on in this patient 's assessment. And inside the home? What responsibilities do they maintain there? Are the changes in decision making, memory problems, are they manifesting in any lost abilities inside the home? Cooking being a potentially high-risk activity, but also using typical appliances and interacting with technology, in a way that we are all increasingly, increasingly doing and increasingly reliant on. And last but not least, you know, maybe the one that everyone wants to think about, well, I can still manage all of my own personal care. Well, good news that many of our patients who have early symptoms can manage their own personal care. Their activities of daily living are not the big problem. But we do want to ask about that specifically. And it's not just about getting in the shower, getting clean, getting out, getting your teeth brushed. Do you need reminders to do that? Do you hop in the shower twice because you forgot that you'd already been in there once during the day? And so, asking some more of those probing questions there can give us a little bit more depth to the interview and really does sort of round out the overall comprehensive history taking in a patient with a memory or cognitive concern. Dr Berkowitz: Fantastic. That was a comprehensive master class on how to both sort of ask the general questions, have you noticed problems in fill in the blank memory, judgment, behavior, orientation, navigation and to sort of drill down on what might be specific examples if they're not offered by the patient or partner to try to say, well, in this domain, tell me how this is going or have you noticed any changes because the everyone's starting from a different level cognitively based on many factors. Right? So, to get a sense of really what the change is in any of these functions and how those have impacted the patient's daily life. So, let's say based on the history, the comprehensive history you've just discussed with us, you do find a number of concerning features in the history that do raise concern for dementia, specifically Alzheimer's disease. How do you approach the examination? We have the MoCA, the mini-mental. We have all of these tools that we use. How do you decide the best way to evaluate based on your history to try to get some objective measure to go along with the more subjective aspects of the history that you've ascertained? Dr Day: And you're honing in on a really good point here, that the history is one part of the interview or the assessment. We really want to build a story and potentially and hopefully a consistent story. If there are memory complaints, cognitive complaints from history, from reliable- that are supported by reliable collateral sources, we're going to expect to see deficits on tests that measure those same things. And so, I think that question about what neuropsychological measures or particular bedside tests can we integrate in our assessment is a good one. But I'll say that it's not the end-all-be-all. And so, if you've got a spouse, someone that lives with an individual for twenty or thirty years, and they're telling you that they notice a change in daily activity and it's impairing their day to day function, or where there's been some change or some concern at work, that's going to worry me more than a low score on a cognitive test with a spouse saying they haven't noticed any day-to-day impact. And so, we're going to take everything sort of in concert and take it all together. And it's part of our job as clinicians to try to process that information. But often we're going to see corroborating history that comes from a bedside test. He named a few that our listeners are probably pretty familiar with. I think they're the most common ones that are used. The Mini-Mental State Exam, been in practice for a long time. All the points add up to thirty and seems to give a pretty good sample of various different cognitive functions. The Montreal Cognitive Assessment, another favorite; a little bit more challenging of a test, I think, if we're if we're looking at how people tend to perform on it. And like the MMSE, points add up to thirty and gives a pretty good sample. There are others that are out there as well, some that are available without copyright and easy for use in clinical practice. The Saint Louis Mental Status Exam comes to mind. All these tests that we're willing to consider kind of share that same attribute. They can be done relatively quickly. They should sample various different aspects of function. There should be some component for language reading, spoken, spoken word, naming items, something that's going to involve some kind of executive function or decision making, problem solving. Usually a memory task where you're going to remember a set of words and be asked to recall that again later. So, learn it, encode it, and recall it later on. And then a few other features, I mean, some of them, these tests, most of these tests use some sort of drawing tasks so that we can see visuospatial perception and orientation questions about date, time, location, sort of the standard format. Any of these tests can be used aptly in your practice. You're going to use the one that you're most comfortable with, that you can administer in a reasonable amount of time and that seems to fit with your patient population. And that's the nuance behind these tests. There are many factors that we have to take into account when we're picking one and when we're interpreting the test results. These tests all generally assume that patients have some level of traditional sociocultural education that is westernized for the most part. And so, not great tests for people that aren't well into integrated into the community, maybe newcomers to the United States, those that have English as a second, third, or fourth language, as many of our patients do. Statements like no ifs, ands, or buts may not be familiar to them and may not be as easy to repeat, recall and remember. And so, we want to weigh these considerations. We may need to make some adjustments to the score, but ideally, we're going to use these tests and they're going to show us what we expect and we're going to try to interpret that together with the history that we've already ascertained. When I obtain that history and I'm thinking about memory loss, I'm going to look at the specific domain scores. And so, if I'm using the mini mental state examination thirty point test, but three questions that relate to relate to recall. Apple, penny, table. And so, depending on how our patients do on that test, they could have an overall pretty good score. Twenty seven. Oh, that looks good. You're in the normal range according to many different status. But if I look at that and there's zero out of three on recall, they could not remember those three items, that may support the emergence of a memory problem. That may corroborate that same thing on the MoCA, which uses five-item recall, and other tests in those same parameters. I mentioned some other caveat cities testing. Are patients who are presenting with prominent language deficits important part of cognition. They can't get the words out. They can't frame their sentences. They may really struggle with these tests because a lot of them do require you to both understand verbal instructions and convey verbal instructions. People with prominent visual problems, either visual problems that come because of their neurodegenerative disease and so part of cognition, visual perceptual problems, or people who simply have low vision. Are there difficulties for that? These tests require many people to read and execute motor commands, to draw things, to follow lines and connect dots, all very difficult in that setting. And so, we have to be cautious about how we're interpreting test results in patients who may have some atypical features or may arrive with sort of preexisting conditions that limit our ability to interpret and apply the test to clinical practice.  Dr Berkowitz: Really fantastic overview of these tests, how to use them, how to interpret them. It's not all about the number. As you said, it depends if all the points are lost in one particular domain, that can be salient and then considering, as you said, the patient 's background, their level of education, where English falls in their first language, second, third or fourth, as you said, and then some of the aspects of the MoCA, right, are not always as culturally sensitive since it's a test designed in a particular context. So, let's say your history and exam are now concerning to you, that the patient does indeed have dementia. Tell us a little bit about the next steps in the laboratory neuroimaging evaluation of such a patient?  Dr Day: I've got a history of memory and thinking problems. I've got some corroborating evidence from bedside cognitive testing, a normal neurological exam. This is where we think about, well, what other tests do we need to send our patients for? Blood testing really can be pretty cursory for most patients with a typical presentation who have typical risk factors, and that can include a thyroid study and vitamin B12. So, measuring those in the blood to make sure that there's no other contributions from potential metabolic factors that can worsen, exacerbate cognitive function. And pretty easy to do for the most part, if patients have other things in their history, maybe they come from a high-risk community, maybe they engage in high risk behaviors, I may think about adding on other tests that associate with cognitive decline. We'll think about the role of syphilis, HIV, other infections. But generally, that's when it's driven by history, not a rule of thumb for me in my typical practice. But beyond the blood tests, neuroimaging, some form of structural brain imaging is important. A CT scan will get you by. So, if you have a patient that can't get in the scanner for one reason or another or won't get in the scanner, or you don't have easy access to an MRI, a CT scan can help us in ruling out the biggest things that we're looking for. That's strokes, hemorrhages, and brain masses. So other things that obviously would take us down a very different path, very different diagnosis and very different treatment approach. An MRI, though, is going to be preferred, not only because it gives us a much higher-resolution view, but also because it helps us to see sort of regional areas of atrophy. It's a sensitive scan to look for small vessel disease, tiny strokes, tiny bleeds, microhemorrhages that again might point towards meteorology for us. Of course, it's better at finding those small masses, whether they be metastasis or primary masses, that could give us something else to consider in our diagnostic evaluation. I get an odd question often from patients, well, can you see Alzheimer's disease on an MRI? And the true answer to that is no, you can't. Can we see the signs of Alzheimer's disease? Sure, in some patients, but really what we see on an MRI is a reflection of neurodegeneration. And so, we see evidence of tissue loss and typically in areas that are most often involved early on in Alzheimer's disease. The hippocampus, the entorhinal areas around the hippocampus, we may see atrophy there. We may see biparietal atrophy, and of course, as the disease progresses, we're going to see atrophy distributed throughout other areas of the brain. But if you're looking for atrophy, you've got to have a pretty good idea what's normal for age and what you expect in that patient population. So, I do encourage clinicians who are assessing patients routinely, look at your own images, look at the images for patients with and without cognitive impairment. So we develop a pretty good sense for what can be normal for age, and of course work with our colleagues in radiology who do this for a living and generally do an excellent job at it as well.  Dr Berkowitz: Perfect. So, you're going to look for the so-called reversible causes of dementia with serum labs, structural imaging to either rule out or evaluate for potential structural causes that are not related to a neurodegenerative condition or patterns of regional atrophy suggestive of a neurodegenerative condition, and maybe that will point us in an initial direction. But the field is rapidly expanding with access to FDG-PET, amyloid PET, CSF biomarkers, genetic testing for APOE 4, probably soon to be serum biomarkers. So, patients may ask about this or a general neurologist referring to your clinic may ask, who should get these tests? When should we think about these tests? How do you think about when to send patients for advanced imaging, CSF biomarkers, genetic testing for APOE 4? Dr Day: It's not that patients may ask about this. Patients will ask about this. And you've probably experienced that in your own world as well. They're going to ask about any of these different biomarkers. Certainly, whatever they've recently read or has been covered on television is going to be common fodder for consideration in the clinic environment. It's important to know what tests you can get, what reliable tests that you can get, and to know the differences between some of these tests when making a recommendation or weighing the pros and cons of doing additional testing. I think common practice principles apply here. Let's order tests that are going to change our next steps in some way. And so, if we have a patient, particularly a patient like the one that we've been talking about: seventy something year old, presenting with memory complaints, they're concerned, the family is concerned. We've got that history, physical exam, and now we may need to really hone in on the etiology. Well, I say may need because for that patient it may be enough to know, yeah, I agree, there's a problem here. And I can say it's an amnestic, predominant, gradual-onset progressive cognitive decline. This is probably Alzheimer disease based on your age. And maybe that's all they want to hear. Maybe they're not ready to pursue additional testing or don't see the value or need for additional testing because it's not going to change their perspective on treatment. In that case, it's okay to apply an often underrated test, which is the test of time. Recognizing this is a patient I can follow. I can see them in six months or twelve months, depending on what your clinic schedule allows. If this is Alzheimer disease, I'm going to expect further gradual progression that may affirm the diagnosis. We can think about symptomatic therapies for a patient like that, perhaps Donepezil as an early, early medication that may help with symptoms somewhat and we can leave it at that for the time being. But there's many scenarios where that patient or the family member says, look, I really need to know. We really want this answer. And as you pointed out, there are good tests and increasingly good tests that we have access to.  Dr Berkowitz: Well, that's a very helpful overview of the landscape of more precise diagnostic testing for Alzheimer disease specifically and how you think about which tests to order and when based on your pretest probability and the patient 's candidacy for some of these new potential therapies. To close here, as you said, treatment is discussed in another podcast. There's another article in this issue. So, we won't get into that today. But let's say you have gotten to the end of the diagnostic journey here. You are now convinced the patient does have Alzheimer's disease. How do you present that diagnosis to the patient and their family? Dr Day: I think here we're going to recognize that different styles align with different patients and families, and certainly different clinicians are going to have different approaches. I do tend to take a pretty direct approach. By the time that patients are coming to see me, they've probably already seen another neurologist or at least another physician who's maybe started some of the testing, maybe even built the foundation towards this diagnosis and shared some indications. Certainly, when they look up my profile before they come to see me, they know what I specialize in and so, they may even have done their own research, which has ups and downs in terms of the questions that I'll be faced with at that point in time. The way I like to start is first acknowledging the symptoms. And the symptoms that the patients have shared with me, recognizing if those symptoms are impacting daily life, how they impacted daily life, and usually using that information to synthesize or qualify the diagnosis. Is there cognitive impairment, yes or no? And at what level is that cognitive impairment? Is this mild cognitive impairment? Is this mild dementia? Is it maybe more moderate or severe dementia? So, using those terms directly with patients and explaining the meaning of them. But I then transition in relatively quickly to the important point of not leaving it at the syndrome, but actually thinking about the cause. Because it is cause that patients come to talk about. And if they don't say that directly, they say it in their next question, which is what are we going to do about it and how are we going to treat this? And so, I will use the information I have available at that time to suggest that based on your age, based on the history, the normal physical examination, the performance and the bedside testing that we've done. And hey, that's pretty normal structural imaging or imaging that only shows a little bit of atrophy in a few areas. I think that this condition is most consistent with symptomatic Alzheimer's disease, mild cognitive impairment due to Alzheimer's disease, or mild dementia due to Alzheimer's disease. And then I'll discuss the next options in terms of testing and try to get a feel of what our patients are thinking about when it comes to treatment. Do they want to be on the cutting edge with brand-new therapies that offer potential benefits but counterbalance by pretty substantial risks that warrant individualized discussions? Are they interested in symptomatic therapies? Would that be appropriate for them? And I can usually round out the discussion with advice that works for everyone. And that's where we talk about the importance of brain health. What are the other things that I should be doing, you should be doing, and our patients and their partners should be doing as well to maintain our brain in its best possible state as we hope that we all continue to age and look towards the future where we maintain our cognition as best as possible? And that is still the goal. Even when we're talking to patients who have neurodegenerative diseases that are working against our efforts, we still want to do what we can to treat other problems, to evaluate for other problems that may be contributing to decline and may be amenable to our management as well.  Dr Berkowitz: Well, thank you so much for taking the time to speak with us today. I've learned a lot from your very nuanced and thoughtful approach to taking the history, performing the examination, making sense of cognitive tests and how they fit into the larger picture of the history and examination, and thinking about which patients might be candidates for more advanced imaging as we try to make a precise diagnosis in patients who may be candidates and interested in some of the potential novel therapies, which we both alluded to a few times, but are deferring to another podcast that we'll delve more deeply into that topic in this series. So, thank you so much again, Dr Day. Again, I've been interviewing Dr Gregory Day from the Mayo Clinic, whose article on Alzheimer's disease 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 so much 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 description: We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Bayan presents a case of headache and seizure to Aye. Neurology DDx Schema Aye Chan Moe Thant ( @AyeThant94 ) Aye is a physician from Myanmar and now working as a clinical research team member at the Department… Read More »Episode 366: Neurology VMR – Headache and Seizure

For certain diagnoses and patients who meet clinical criteria, neuromodulation can provide profound, long-lasting relief that significantly improves quality of life. In this episode, Aaron Berkowitz, MD, PhD, FAAN speaks with Prasad Shirvalkar, MD, PhD, author of the article “Neuromodulation for Neuropathic Pain Syndromes,” in the Continuum® October 2024 Pain Management in Neurology 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. Shirvalkar is an associate professor in the Departments of Anesthesia and Perioperative Care, Neurological Surgery, and Neurology at Weill Institute for Neurosciences at the University of California, San Francisco in San Francisco, California. Additional Resources Read the article: Neuromodulation for Neuropathic Pain Syndromes Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Guest: @PrasadShirvalka 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 Berkowitz: This is Dr Aaron Berkowitz, and today I'm interviewing Dr Prasad Shirvalkar about his article on neuromodulation for painful neuropathic diseases, which appears in the October 2024 Continuum issue on pain management in neurology. Welcome to the podcast, and if you wouldn't mind, please introducing yourself to our listeners.  Dr Shirvalkar: Thanks, Aaron. Yes, of course. So, my name is Prasad Shirvalkar. I'm an associate professor in anesthesiology, neurology and neurological surgery at UCSF. I am one of those rare neurologists that's actually a pain physician.  Dr Berkowitz: Fantastic. And we're excited to have you here and talk to you more about being a neurologist in in the field of pain. So, you wrote a fascinating article here about current and emerging neuromodulation devices and techniques being used to treat chronic pain. And in our interview today, I'm hoping to learn and for our listeners to learn about these devices and techniques and how to determine which patients may benefit from them. But before we get into some of the clinical aspects here, can you first just give our listeners an overview of the basic principles of how neuromodulation of various regions of the nervous system is thought to reduce pain? Dr Shirvalkar: Yeah, I would love to try. But I will promise you that I will not succeed because I think to a large extent, we don't understand how neuromodulation works to treat pain, to describe or to define neuromodulation. Neuromodulation is often described as using electrical stimuli or a chemical stimuli to alter nervous system activity to really influence local activity, but also kind of distant network activity that might be producing pain. On one level, we don't fully understand how pain arises, specifically how chronic pain arises in the nervous system. It's a huge focus of study from the NIH Heal Initiative and many labs around the world. But acute pain, which is kind of when you stub your toe or you burn your finger, is thought to be quite different from the changes over time and the kind of plasticity that produces emotional, cognitive and sensory dimensions. Really what I think is its own disease, chronic pain, of which there are multiple syndromes when we use neuromodulation, either peripheral nerve stimulation or electrical spinal cord stimulation. One common or predominant theory actually comes from a paper in science from 1967 and people still use it, foundational theory and it's called the gate control theory. Two authors, Melzack and Wall, postulated that at the spinal level, there are, there's a local inhibitory circuit or, you know, there's a local circuit where if you provide input to either peripheral nerves or either spinal cord ascending fibers that to kind of summarize it, there's only so much bandwidth, you know, that nerves can carry. And so that if you literally pass through artificial signals electrically, that you will help gate out or block natural pathological but natural pain signals that might be arising from the periphery or spinal cord. So, you know, one idea is that you are kind of interfering with activity that's arising for chemical neuromodulation. The most common is something known as intrathecal drug infusion drug delivery ITTD for that we quite literally put a catheter in the spinal fluid, you know, at the level of the dorsal horn neurons that we think are responsible for perpetuating or creating the pain. Where's the pain generator? And you really, you can infuse local anesthetic, you can infuse opioids. And what's nice is you avoid a lot of systemic side effects and toxicity because it goes right to the spinal cord, you know, by infusing in the fluid. So there's a couple of modalities, but I will say just, like maybe all of our living experience, pain is in the brain. And so, we don't really understand, I would say, what neuromodulation is doing to the higher spinal or brain levels. Dr Berkowitz: Fascinating topic. And yeah, very interesting to hear both what our current understanding is that some of our current understanding is based on data that's 60 years old and that we're actually probably learning about pain by using these modulation techniques, even though we don't really understand how they might be working. So interesting feedback loop there as well as in as in the as in this land. So, your article very nicely organizes the neuromodulation techniques from peripheral to central. So, encourage our listeners to check out your article. And first before we get into some of the clinical applications, just to give the listeners the lay of the land, can you sort of lay out the devices and techniques available for treating pain at each level of the neuroaxis? We'll get into some of the indications in patient selection in a moment, but just sort of to lay out the landscape. What's available that you and your colleagues can use or implant at different levels when we're thinking of referring patients too? Dr Shirvalkar: Absolutely. So, starting from the least invasive or you know, over the counter patients can purchase themselves a TENS machine. Many folks listening to this have probably tried a TENS machine in the past. And the idea is that you put a couple of pads, at least two. So you have like a dipole or you have a positive and a negative lead and you basically inject some current. So, the pads are attached to a battery and you can put these pads over muscle. If you have areas where myofascial pain or sore muscles, you can put them, frankly, over nerves as well and stimulate nerves that are deeper. Most TENS machines kind of use electrical pulses that occur at different rates. You change the rates, you can change the amplitude and patient can kind of have control for what works best. Then getting slightly more invasive, we can often stimulate electrically peripheral nerves. To do this we implant through a needle, a small wire that consists of anywhere from one electrical contact to four or even eight electrical contact. What I think is particularly cool, like TENS, which is transcutaneous electrical nerve stimulation that goes through the skin. Peripheral nerve stimulation aims to stimulate nerves, but you don't have to be right up against the nerve. So, yeah. We typically do this under an ultrasound and you can visualize a nerve like the sciatic nerve, peroneal nerve, or you know, even if someone has an ulnar or a neuropathy, you know, that's the compression. There's a role obviously for surgery and release, but if they have predominantly pain, it's not related to a mechanical problem per se, you could prevent a wire from a peripheral nerve stimulator as far as one centimeter from a nerve and it'll actually stimulate that that modulated and then, you know, kind of progressing even more deeply. The spinal cord stimulation, SCS, it's probably the most ubiquitous or popular form of neuromodulation for pain. People use it for all kinds of diseases. But what it roughly involves is a trial period, which is a placement of either two cylindrical wires, not directly over the spinal cord, but actually in the epidural space, right? So, it's kind of like when you get an epidural injection or doing labor and delivery, when women get epidural catheters, placing spinal cord stimulator leads in that same potential space outside the dura, and you're stimulating through the dura to actually target the ascending dorsal column fibers. And so, you do a trial period or a test drive where the patients get these wires put in. They're coming out of the skin, they're connected to a battery, and they walk around at home for about a week, take careful notes, check in with them, and they keep a diary or a log about how much it helps. Separately. I will say it's hard to distinguish this, the placebo effect often, but you know, sometimes we want to use the placebo effect in clinical practice, but it is a concern, you know, with such invasive things. But you know, if the trial works well, right, you basically can either keep the leads where they are and place a battery internally. And it's for neurologists. You're familiar with deep brain stimulation. These devices are very similar to DVS devices, but they're specifically made for spinal cord stimulation. And there's now like seven companies that offer manufacturers that offer it, each with their own proprietary algorithm or workflow. But going yet more invasive, there is intrathecal drug delivery, which I mentioned, which involves placement of the spinal catheter and infusion of drug into spinal fluid. You could do a trial for that as well. Keep a patient in the hospital for a few days. You've all probably had experience with lumbar drains. It's something real similar. It just goes the other way. You know, you're infusing drugs, and it could also target peripheral nerves or nerve roots with catheters, and that's often done. And last but not least, there's brain stimulation. Right now, it's all experimental except for some forms of TMS or transcranial magnetic stimulation, which is FDA approved for migraine with aura. There are tens machine type devices, cutaneous like stimulators where you can wear on your head like a crown or with stickers for various sorts of migraines. I don't really talk about them too much in in the article, but if there's a fast field out there for adjunctive therapy as well,  Dr Berkowitz: Fantastic. That's a phenomenal overview. Just so we have the lay on the land of these devices. So, from peripheral essentially have peripheral nerve stimulators, spinal cord stimulators, intrathecal drug delivery devices and then techniques we use in other areas of neurology emerging for pain DBS deep brain stimulation and TMS transcranial magnetic stimulation. OK let's get into some clinical applications now. Let's start with spinal cord stimulators, which - correct me if I'm wrong - seem to be probably the most commonly seen in practice. Which patients can benefit from spinal cord stimulators? When should we think about referring a patient to you and your colleagues for consideration of implantation of one of these spinal cord stimulator devices?  Dr Shirvalkar: So, you know, it's a great question. I would say it's interesting how to define which patients or diagnosis might be appropriate. Technically, spinal cord stimulators are approved for the treatment of most recently diabetic peripheral neuropathy. And so, I think that's a really great category if you have patients who have been failed by more conservative treatments, physical therapy, etcetera, but more commonly even going back, neuropathic low back pain and neuropathic leg pain. And so, you think about it and it's like, how do you define neuropathic pain. Neuropathic pain is kind of broadly defined as any pain that's caused by injury or some kind of lesion in the somatosensory nervous system. We now broaden that to be more than just somatosensory nervous system, but still, what if you can't find a lesion, but the pain still feels or seems neuropathic. Clinically, if something is neuropathic, we often use certain qualitative descriptors to describe that type of pain burning, stabbing, electric light, shooting radiates. There's often hyperpathia, like it lingers and spreads in space and time as opposed to, you know, arthritis, throbbing dull pain or as opposed to muscle pain might be myofascial pain, but sometimes it's hard to tell. So, there aren't great decision tools, I would say to help decide. One of the most common syndromes that we use spinal cord stimulation for is what used to be called failed back surgery syndrome. We never like to, we now try to shy away from explicitly saying something is someone has failed in their clinical treatment. So, the euphemism is now, you know, post-laminectomy syndrome. But in any case, if someone has had back surgery and they still have a nervy or neuropathic type pain, either shooting down their legs and often there's no evidence on MRI or even EMG that that something is wrong, they might be a good candidate, especially if they're relying on long term medications that have side effects or things like full agonist opioids, you know that that might have side effects or contraindication. So, I would say one, it's not a first line treatment. It's usually after you've gone through physical therapy for sure. So, you've gone through tried some medications. Basically, if chronic pain is still impacting your life and your function in a meaningful way that's restricting the things you want to do, then it it's totally appropriate, I think, to think about spinal cord stimulation. And importantly, I will add a huge predictor of final court stimulation success is psychological composition, you know, making sure the person doesn't have any untreated psychological illness and, and actually making sure their expectations going in are realistic. You're not going to cure anyone's pain. You may and that's, you know, a win, but it's very unlikely. And so, give folks the expectation that we hope to reduce your pain by 50% or we want you to list personally, I like functional goals where you say what is your pain preventing you from doing? We want to see if you can do X,Y, and Z during the trial period. Pharmacostimulation right now. Yeah. Biggest indication low back leg pain, Diabetic peripheral neuropathy. There is also an indication for CRPS, complex regional pain syndrome, a lesser, I'd say less common but also very debilitating pain condition. For better or worse. Tertiary quaternary care centers. You often will see spinal cord stem used off label for neuropathic type pain syndromes that are not explicitly better. That may be for example, like a nerve injury that's peripheral, you know, it's not responding. A lot of this off label use is highly variable and, you know, on the whole at a population level not very successful. And so, I think there's been a lot of mixed evidence. So, it's something to be aware about.  Dr Berkowitz: That's a very helpful framework. So, thinking about referring patients to who have most commonly probably the patients with chronic low back pain have undergone surgery, have undergone physical therapy, are on medications, have undergone treatment for any potential psychological psychiatric comorbidities, and yet remain disabled by this pain and have a reasonable expectation and goals that you think would make them a good candidate for the procedure. Are those similar principles to peripheral nerve stimulation I wasn't familiar with that technique, I'm reading your article, so are the principles similar and if so, which particular conditions would potentially benefit from referral for a trial peripheral nerve stimulation as opposed to spinal cord stimulation?  Dr Shirvalkar: Yeah, the principles are similar overall. The peripheral nerve stimulation, you know, neuropathic pain with all the characteristics you listed. Interestingly enough, just like spinal cord stim, most insurances require a psychological evaluation for peripheral nerve stim as well. And we want to make sure again that their expectations are reside, they have good social support and they understand the kind of risks of an invasive device. But also, for peripheral nerve stem, specifically, if someone has a traumatic injury of an individual peripheral nerve, often we will consider it seeing kind of super scapular stimulation. Often with folks who've had shoulder injuries or even sciatic nerve stimulation. I have done a few peroneal nerve stimulations as well as occipital nerve stimulation from migraine, so oxygen nerve stimulation has been studied a lot. So, it's still somewhat controversial, but in the right patient it can actually be really helpful. Dr Berkowitz: Very helpful. So, these are patients who have neuropathic pain, but limited to one peripheral nerve distribution as opposed to the more widespread back associated pains, spine associated pains. Dr Shirvalkar: Yeah, Yeah, that's right. And maybe there's one exception actually to this, which is brachial plexopathy. So, you know, folks who've had something like a brachial plexus avulsion or some kind of traumatic injury to their plexus, there is I think good Class 2 evidence that peripheral nerve stem can work. It falls under the indication. No one is as far as to my knowledge, No one's done an explicit trial, you know PNS randomized controlled trial. Yeah, that's, you know, another area one area where PNS or peripheral nerve stems emerging is actually, believe it or not in myofascial low back pain to actually provide muscle stimulation. There are some, there's a company or two out there that seeks to alter the physiology of the multifidus muscle, one of your spinal stabilizer muscles to really see if that can help low back pain. And they've had some interesting results.  Dr Berkowitz: Very interesting. You mentioned TENS units earlier, transcutaneous electrical nerve stimulation as something a patient could get over the counter. When would you encourage a patient to try TENS and when would you consider TENS inadequate and really be thinking about a peripheral nerve stimulator?  Dr Shirvalkar: Yeah, you know TENS we think of as really appropriate for myofascial pain. Folks who have muscular pain, have clear trigger points or taught muscle bands can often get relief from TENS If you turn a TENS machine up too high, you'll actually see muscle infection. So, there's an optimal level where you actually can turn it up to induce, like, a gentle vibration. And so folks will feel paresthesia and vibrations, and that's kind of the sweet spot. However, I would say if folks have pain that's limited or temporary in time or after a particular activity, TENS can be really helpful. The unfortunate reality is TENS often has very time-limited benefits - just while you're wearing it, you know? So, it's often not enduring. And so that's one of the limitations. Dr Berkowitz: That's helpful to understand. We've talked about the present landscape in your article, also talk a little bit about the future and you alluded to this earlier. Tell us a little bit about some off label emerging techniques that we may see in future use. Who, which types of patients, which conditions might we be referring to you and your colleagues for deep brain stimulation or transcranial magnetic stimulation or motor cortex stimulation? What's coming down the pipeline here?  Dr Shirvalkar: That's a great question. You know, one of my favorite topics is deep brain stimulation. I run the laboratory that studies intracranial signals trying to understand how pain is processed in the brain. But, believe it or not, chronic pain is probably the oldest indication for which DBS has been studied. the first paper came out in 1960, I believe, in France. And you know, the, the original pivotal trials occurred even before the Parkinson's trial and so fell out of favor because in my opinion, I think it was just too hard or too difficult or a problem or too heterogeneous. You know, many things, but there are many central pain syndromes, you know, poststroke pains, there's often pains associated with Parkinson's disease, epilepsy, or other brain disorders for which we just don't have good circuit understanding or good targets. So, I think what's coming down the pipeline is a better personalized target identification, understanding where can we stimulate to actually alleviate pain. The other big trend I think in neuromodulation is using closed loop stimulation which means in contrast to traditional electrical stimulation which is on all the time, you know it's 24/7, set it and forget it. Actually, having stimulation respond or adapt to ongoing physiological signals. So that's something that we're seeing in spinal cord stem, but also trying to develop in deep brain stimulation and noninvasive stimulation. TMS is interestingly approved for neuropathic pain in Europe, but not approved by the FDA in the US. And so I think we may see that coming out of pipeline broader indication. And finally, MR guided focused ultrasound is, is a kind of a brand new technique now. You know, focused ultrasound lesions are being used for essential tremor without even making an incision in the skull or drilling in skull. But there are ways to modulate the brain without lesioning. And, you know, I think a lot of research will be emerging on that in the next five years for, for pain and many other neuronal disorders. Dr Berkowitz: That's fascinating. I didn't know that history that DBS was first studied for pain and now we think of it mostly for Parkinson's and other movement disorders. And now the cycle is coming back around to look at it for pain again. What are some of the targets that are being studied that are thought to have benefit or are being shown by your work and that of others to have benefit as far as DBS targets for, for chronic pain? Dr Shirvalkar: You know, that's a great question. And so, the hard part is finding one target that works for all patients. So, it may actually require personalization and actually understanding what brain circuit phenotypes do you have with regards to your chronic pain and then based on that, what target might we use? But I will say the older targets. Classical targets were periaqueductal gray, which is kind of the opioid center in your brain. You know, it's thought to just release large amounts of endogenous opioids when you stimulate there and then the ventral pusher thalamus, right. So, the sensory ascending system may be through gait control theory interferes with pain, but newer targets the answer singlet there's some interest in in stimulating there again, it doesn't work for everybody. We found some interesting findings with the medial thalamus as well as aspects of the caudate and other basal ganglion nuclei that we hopefully will be publishing soon in a data science paper.  Dr Berkowitz: Fantastic. That's exciting to hear and encourage all of our listeners to check out your article. That goes into a lot more depth than we had time to do in this short interview, both about the science and about the clinical indications, pros and cons, risks and benefits of some of these techniques. So again, today I've been interviewing Dr Prasad Shirvalkar, whose article on neuromodulation for painful neuropathic diseases appears in the most recent issue of Continuum on pain management in neurology. Be sure to check out Continuum Audio episodes from this and other issues. And thank you again to our listeners for joining today.  Dr Shirvalkar: Thank you for having me. It was an honor. 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 title: Episode 359 Neurology VMR – altered mental status Episode description: We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Vale presents a case of altered mental status to Aye. Neurology DDx Schema Aye Chan Moe Thant Aye graduated from University of Medicine, Mandalay, Myanmar, and has been… Read More »Episode 359: Neurology VMR – altered mental status

Episode title: Episode 351 Neurology VMR – headache and double vision Episode description: We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Aye presents a case of bilateral lower limb weakness to Valeria. Neurology DDx Schema   Aye Chan Moe Thant Aye graduated from University of Medicine, Mandalay, Myanmar, and… Read More »Episode 351: Neurology VMR – headache and double vision

Autoimmune neurology is a rapidly evolving subspecialty that focuses on neurologic disorders with atypical immune responses. In this episode, Aaron Berkowitz, MD, PhD FAAN, speaks with Sean J. Pittock, MD, an author of the article “Overview and Diagnostic Approach in Autoimmune Neurology,” in the Continuum August 2024 Autoimmune Neurology issue. Dr. Berkowitz is a Continuum® Audio interviewer and professor of neurology at the University of California San Francisco, Department of Neurology and a neurohospitalist, general neurologist, and a clinician educator at the San Francisco VA Medical Center and San Francisco General Hospital in San Francisco, California. Dr. Pittock is the director for the Center for Multiple Sclerosis and Autoimmune Neurology at Mayo Clinic in Rochester, Minnesota. Additional Resources Read the article: Overview and Diagnostic Approach in Autoimmune Neurology Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Transcript Full 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 Berkowitz: This is Dr Aaron Berkowitz, and today, I'm interviewing Dr Sean Pittock about his article, “Introduction to Autoimmune Neurology and Diagnostic Approach”, which he wrote with his colleague, Dr Andrew McKeon. This article is a part of the August 2024 Continuum issue on autoimmune neurology. Welcome to the podcast, Dr Pittock. Could you introduce yourself to our audience?    Dr Pittock: Well, thank you very much, Dr Berkowitz. So, yeah, I'm a neurologist at the Mayo Clinic. I direct the neuroimmunology laboratory with Dr McKeon and Dr Mills here, and I have also been very much involved in the autoimmune neurology section at the American Academy of Neurology.    Dr Berkowitz: So, many of you probably know Dr Pittock - or if you don't know, you've certainly diagnosed diseases that he has described and written about, and so it's a real honor to get to talk to you today and pick your brain a little bit about some of these complex diseases. So, autoimmune neurology is certainly one of the most exciting subspecialties of our field. I feel like when I talk to students and they ask me to make a case for why they should consider neurology as a career, I tell them, “Of course, I have many reasons I love neurology”, but one thing I mention is that, although many other fields of medicine may have made incredible advances as far as treatments, I can't think of too many other fields outside neurology where entirely new diseases have been described since I've been in training and come out of training - and many of those have been in your field of autoimmune neurology. I can think of cases where I've heard you or one of your colleagues on a neurology podcast describing a new antibody, new disease, and a few weeks later, we see that disease and give a patient a diagnosis that had been elusive from other physicians and hospitals. It's a very exciting, gratifying area. It's also daunting, like, every time I go to the AAN and hear one of your colleagues, there's a new disease, and we realize, “Oops! Was I missing that?” or, “Am I going to see this?” And so, hoping to pick your brain a bit today about some of the key concepts and how to keep them in mind so our listeners can recognize, diagnose, and treat these conditions, even if they can't remember every single antibody in your article and all the new ones you and your colleagues will probably discover between now and when this, um, podcast is released. So, before we get into some of the important clinical aspects of these conditions, could you just lay out sort of the broad breaststrokes, the lay of the land of cell-mediated versus antibody-mediated paraneoplastic versus nonparaneoplastic cell surface versus intracellular - how can we sort of organize this area in our minds?    Dr Pittock: Yeah. It's complex, and it's really an evolving story. But the importance, really, from the perspective of the reader and the perspective of the clinician is that we're talking about disorders where we can actually do something - we can actually impact patients.  And we think about the concept of stopping and restoring in neurology now. We're talking about disorders where we have the potential to stop these inflammatory immune-mediated disorders and, potentially, by stopping early, we may be able to restore function - so, a really important new and evolving field in neurology, because you don't want to miss these conditions. Trying to get your head around the complexity of these entities is difficult, but what we've done in this chapter is, really, to try and lay the groundwork for the following chapters, but provide somewhat of a simplistic approach, but a practical approach that really, I think, can help clinicians. So, the way I think of it, a lot of autoimmune neurology really has stemmed from the discovery of antibodies that cause neurological disease, and the examples of those would be going back to myasthenia gravis (with antibodies to the acetylcholine receptor), going back to Lambert-Eaton syndrome. And then, you know, even if you go back to the older traditional paraneoplastic disorders (the Hu, the Ri, the Yo), at the end of the day, you really have two essential entities, if you want to be very simple. The first is disorders that are caused by an antibody, and the second are disorders where the antibodies you detect are not causing the disorder, but they're telling you that there's predominantly a cellular or T-cell mediated attack of the nervous system. And I think thinking about the diseases in those kind of simple terms helps us when we think about what would be the best treatment to use in these types of cases.   Dr Berkowitz: Fantastic. I think that's very helpful. And just to make sure it's clear in the minds of our listeners when we're dividing into these sort of causative antibodies versus antibodies that might be, uh (I don't know if I'm using the word properly), but, sort of epiphenomena (or they're present, but they're not causative) as you said, can you just give some examples of the ones on either side and how making this distinction helps us in practice?    Dr Pittock: Yes. So, antibodies that are causative of disease - I think, you know, the one that I've done a lot of work on is in neuromyelitis optica, where you have antibodies that are targeting a water channel that sits on an astrocyte, and so it causes NMOSD, or what we consider an autoimmune astrocytopathy. And we know that when the antibody binds to the target, many things can happen. So, when aquaporin-4 antibodies bind to aquaporin-4, they can do a lot of things. They can cause internalization, they can activate complement that results in the killing of the cell - but there can be other situations. For example, when NMDA-receptor antibodies bind to the NMDA receptor, then a variety of different things can occur different to water channel autoimmunity - where, for example, the receptor (the NMDA receptor) is downregulated off the cell surface, and that results, to some extent, in the neuropsychiatric phenomenon that we see in NMDA-receptor autoimmunity. And, obviously, when you have a situation where the antibodies are causing the disease, removal of those antibodies, or the reduction in the production of those antibodies, is going to help patients. Now, on the other side, we have antibodies that we detect in the blood or in the spinal fluid, and those antibodies are targeting proteins that are inside the cell - so those antibodies we don't consider as being pathogenic. Now, remember, there are sometimes situations where proteins that are inside the cell occasionally can be available for antibodies to bind at certain situations. So, for example, in the synapse, amphiphysin or the septins, may at times become available. And so, sometimes, there are targets or antibodies that are somewhat in between those two simplistic concepts. But when we're talking about antibodies that are targeting proteins on the inside of the cell, remember that antibodies don't just suddenly occur. There's a whole process of presentation of target antigen at the lymph node, and then both a T- and a B-cell response. The B-cell response potentially produces the antibodies but also triggers and stimulates T-cells, and those T-cells then go on to cause the disease. And those T-cells are very problematic, because those classical paraneoplastic and the newer ones we've described (and many have described) - these are associated with quite severe neurological disability, and they're very, very difficult to treat. And if you ask me, “Where is the holy grail of autoimmune neurology therapeutic research?” It's in trying to actually figure out ways of treating the predominantly T-cell mediated paraneoplastic and autoimmune neurological disorders. We're making great headway in terms of the treatments of the antibody-mediated neurological disorders.   Dr Berkowitz: That's a helpful overview. So, sticking with this framework, you mentioned as sort of the “causative antibody” category and the antibodies that are predominantly for intracellular antigens, but not believed to be causative - I want to make sure I'm understanding this correctly and we can convey it to our listeners - I believe you said in your paper, then, that the antibodies that are predominantly causative are more likely to be associated with conditions that are very treatable, as compared to the intracellular antibodies that are not thought to be causative, as you just said the disability can be irrecoverable or very hard to treat. And I believe another theme in your paper that you brought out is the antibodies that tend to be causative tend to be cell surface and tend to be less likely to be associated with underlying cancer (although not a perfect rule), and the intracellular antigens more commonly associated with cancer in those cases to look very hard for a cancer before giving up. Are those themes that I understand them from your paper properly, or anything else to add there?    Dr Pittock: Yes, I think that that's exactly the message that we were trying to get across, so that's good news that you've picked up on the themes. I think, yeah, in simple terms, remember that when a cytotoxic T-cell identifies the peptide that its T-cell receptor will target, the ultimate outcome is poor, all right? T-cells are like the marines - they don't mess around. Once they find their target, they eliminate that target, and so, it's really difficult to treat those types of diseases if you get them late. And most patients with cytotoxic T-cell mediated paraneoplastic neurological disorders, oftentimes, by the time they get to a center of excellence, the boat has left the dock in many respects - in other words, it's too late. So, you know, I will often see patients, for example, with progressive cerebellar degeneration (say, in the context of Purkinje cell autoantibody type 1 antibodies and a breast cancer), and if those patients are in a wheelchair at the time that I see them, there's very, very little that we can do. So, you really want to try and get that patient into the office, you know, when they're using a cane (or not), and then, potentially, you have the opportunity - using very aggressive immunosuppressive medications - to make a difference. And that is quite different to other scenarios, where, for example, if you have NMDA-receptor encephalitis - as many of the readers will know, this is a condition that is very treatable, and most patients do very well, because the antibodies, they're disrupting function, but they're not killing the neuron, as we see in those more aggressive, paraneoplastic cytotoxic T-cell mediated diseases.   Dr Berkowitz: Also, in terms of searching for an underlying cancer, another theme in your paper as I understood (but want to make sure I'm understanding and conveying to our listeners and hear your thoughts), that the cell surface and treatable antibody-mediated syndromes, as you mentioned (NMO, NMDA) tend to be less associated with underlying cancers (although can be), whereas the intracellular antigens, um, a much higher percentage of those patients are going to end up having underlying cancers. Is that correct, or any notable exceptions to be aware of in that framework?    Dr Pittock: Yeah, I think the major exception to the rule for the antibodies that are targeting intracellular antigens is the GAD65 antibody story. We generally don't consider the stiff person syndrome, cerebellar ataxia, or other autoimmune neurological disorders associated with very high levels of GAD65 antibodies - those are generally not paraneoplastic. And then there are always exceptions on both sides. You know, one of the benefits of understanding the implications of certain antibodies is trying to understand, you know, what is the likelihood of identifying a malignancy, which antibodies are high-risk antibodies (in other words, high-risk paraneoplastological disorders), and which are low risk in terms of cancer? And, you know, age and the demographic of the individual is often important, because we know, for example, with NMDA-receptor antibodies, the frequency of ovarian teratoma varies with the age of the patient.   Dr Berkowitz: Fantastic. And we encourage our listeners to read your articles – certainly, some very helpful tables and figures that help to elucidate some of these broad distinctions Dr Pittock is making - but just to summarize for the antibody-related part of autoimmune neurology, we have one category of cell-surface antibodies and another of intracellular antibodies. Both can cause very severe and varied neurologic presentations, but the cell surface tend to be more treatable, less likely to be associated with the underlying cancer, and the intracellular less treatable, more likely to be associated with the underlying cancer - but, as with everything in neurology and medicine, exceptions on both sides. Is that a fair aerial view of some of the details we've discussed so far, Dr Pittock?    Dr Pittock: Yeah, I think so. I mean, I also think that, you know, not only, at least, for the antibody-mediated disorders (you know, as we discussed) we have drugs that will reduce the production of those antibodies, but we're also learning a lot more about the cytokine and chemokine signatures of these disorders. For example, NMO, water-channel antibody-mediated diseases are associated with elevated levels of IL-6. We know, for example, in LGI1 encephalitis and other encephalitides, that IL-6 also is elevated at the time of that encephalitic process. And so, the potential to target IL-6 with, you know, drugs that inhibit IL-6 and the IL-6 receptor, these potentially have, you know, a role to play in the management of these types of patients - whereas in the T-cell mediated disorders, you know, no advance has been made in the treatment of those conditions, I would say, in over 50 years. So, for example, the standard of treatment is steroids and then drugs that impact the bone marrow, and so we really haven't moved forward in that respect. And that, I think, is an area that really needs drive and enthusiastic out-of-the-box thinking so that we can try to get better treatments for those patients.   Dr Berkowitz: This has been a helpful overview. I look to dive into some of the scenarios that frontline practitioners will be facing thinking about these diseases. An important point you make in your article is that autoimmune and antibody-mediated neurologic syndromes can affect any level of the neuraxis. Even just our discussion so far, you've talked about anti-NMDA receptor encephalitis, you've talked about myasthenia gravis (that's at the neuromuscular junction), you've talked about paraneoplastic cerebellar degeneration - there can be an “itis” of any of our neurologic structures and that “itis” can be antibody-mediated. So, one of the key messages you give us is, one, that these are sort of in the differential diagnosis for any presenting neurologic syndrome, and, two, sort of one of the key features of the history, really, to keep in mind (since we could be anywhere along the neuraxis) is the subacute presentation when this should really sort of be top of mind in our differential diagnosis - so, many of these patients are going to be mystery cases at the outset. And one striking element you bring out in the paper is that, sometimes, the MRI, CSF, electrophysiology studies may be normal or nonspecifically abnormal, and although it's very helpful when we can send these antibody panels out, in some cases, resources are limited or institutions have certain thresholds before you can send these out (because neurologists love to send them in). Sometimes, they are not necessarily appropriate. So, love to hear your thoughts on when we should be sending these panels. What are some clues? Um we have a subacute neurologic presentation at any level of the neuraxis, and when it's not anti-NMDA receptor encephalitis, that is sort of a clear phenotype in many cases. How you would approach a patient, maybe, where the MRI is either normal or borderline abnormal (or people are squinting at the medial temporal lobe and saying, “Maybe they're a little brighter than normal”), CSF is maybe normal or nonspecifically, um, and the protein is a little high, but no cells? What clues do you use to say, you know, “These are the patients where we should be digging deep into antibody panels and making sure these are sent and not miss this diagnosis?”    Dr Pittock: Well, thank you. That's a good question. So, I think, you know, first of all, these are complex cases. So, the patient is sitting in front of you and you're trying to figure out, first of all, Is this a hardware or a software problem? Are we definitively dealing with an encephalitis or an organic neurological entity that's immune-mediated? And, you know, the way I think of it is, for me, you see a patient, it's a twenty-five-piece jigsaw puzzle and you've got two pieces, and you're trying to say, “Well, if I step back and look at those two pieces, do I have any sense of where we're going with this patient?” So, the first thing you need to do is to collect data, both the clinical story that the patient tells you (and I think you make the good point that that subacute onset is really a big clue), but subacute onset, also fluctuating course, sometimes, can be important. The history of the patient - you know, Is the patient somebody who has a known history of autoimmune disease? Because we know that patients that have thyroid autoimmunity are more likely to have diabetes, they're more likely to have gastrointestinal motility or dysmotility, they're more likely to have a variety of different immune-mediated conditions. So, is there a family history or a personal history of autoimmunity? Is the patient at high risk for malignancy? Are there clues that this potentially could be a tumor-initiated immune process affecting the nervous system? The neurological exam also is extremely important because, again, that helps you, first of all, kind of define and get some objectivity around what you're dealing with. So, does the patient have hyperreflexia? Are there signs that there is neurological involvement? And then, really, what I think we need to do is to try and frame the predominant neurological presentation. So, what is the major issue? Because a lot of these patients will have multiple complaints, multiple symptoms, and it's very important to try and identify the major presentation. And that's important, because the neural autoantibody tests are now presentation-defined - in other words, they're built around the neurological presentation, because the old approach of just doing, apparently, a plastic evaluation is gone, because we've got to a stage where we have now so many neural antibodies, you can't test every single neural antibody. So, if you're suspecting that there may be an autoimmune neurological component, then you really need to think about what would be the most appropriate comprehensive evaluation I need to do for this patient. So, for example, if a patient comes in with a subacute-onset encephalopathy, you're probably going to want the autoimmune encephalitis evaluation, and then you have to pick whether it's going to be serum or spinal fluid - and as we outlined in the paper, there are certain antibodies that are better detected in serum versus spinal fluid. So, for example, in adults over the age of 50, LGI1 is much more accurately detected in serum than spinal fluid, and the absolute opposite is true for NMDA-receptor antibody detection. One of the most important components of the neurological evaluation is the spinal fluid, but actually looking at the white cell count - and in fact, sometimes, it's quite interesting to me that I'll often see patients referred with a diagnosis of encephalitis and autoimmune encephalitis, and yet they haven't had a spinal fluid examination. So, the presence of a white cell count, you know, greater than five is hugely helpful - it's like two pieces of that twenty-five-piece jigsaw, because that really tells you that there is something inflammatory going on. And now, in terms of imaging, you're right - some patients will have normal MRI. And if you really do think that there's evidence of - you know, for example, you do an MRI, but you're getting a good sense that there's a temporal lobe seizure occurring, MRI looks normal, the EEG shows some abnormalities in the mesial temporal area - you know, considering additional imaging modalities (like PET scan of the brain), I think, is reasonable. We know that in NMDA-receptor encephalitis cases, 30% of patients will have normal MRI but they'll often have abnormalities on the PET scans. So, I think, what we do is we try to gather data and gather information that allows us to add in pieces of that jigsaw so that, eventually, after we've done this evaluation, we can see now we have ten pieces. If we step back, we say, “Yes, now we know what this condition is”, and then we essentially plan out the therapeutic approach dependent on what we've found. In terms of identification of underlying malignancy, you know, different people have different approaches. Our approach generally has been to try to get a PET-CT scan of the body as our first go-to test, because, actually, we found that CT chest abdomen and pelvis really actually delivers the same amount of radiation - and from a cost perspective, it's about the same - and we have found that PET-CTs really do provide a higher sensitivity for cancer detection.   Dr Berkowitz: Perfect. A lot of very helpful clinical pearls there. So, in closing, Dr Pittock, I've learned a lot from you today. I'm sure our listeners will as well. What does the future hold in this field? What's coming down the pipeline? What are we going to be learning from you and your colleagues that are going to help us take care of patients with these diseases going forward?    Dr Pittock: Well, thank you, Dr Berkowitz, for that question. I think the future is very bright and very exciting, and, hopefully, some of the more junior members will be enthused by this Continuum series, and, hopefully, we'll go into this area. So, let's talk about the future. The future, I think, is going to be of great interest. Firstly, there's going to be continued discovery of novel biomarkers, and the reasons for that is because of the technical and technological advances we've seen. So, for example, there have been many, many antibodies discovered by us and others that have been discovered on the basis of, for example, phage technology. In fact, the Kelch 11 biomarker discovery in collaboration with UCSF and our group was done on the basis of Joe DeRisi and Michael Wilson's phage approach. And we're actually using that now at Mayo Clinic, and we've discovered about three or four new antibodies just in the last couple of years using this technology (and that here is led by John Mills and Div Dubey). And then, we're also going to see, I think, the evolution of protoarrays much more in biomarker discovery, so, we'll have more antibodies, and again, I think, generally, those antibodies will fall into the two categories we kind of described - so, you know, in terms of the approach to those conditions, maybe not so much change. I do think, though, that the introduction and the utility of comprehensive cytokine and chemokine analysis in the future will assist us in making diagnoses of seronegative encephalitis, but also potentially will direct therapy. So, for example, cytokine A is elevated - maybe that would be a potential target for therapy that's available for these patients with rare and potentially very disabling disorders. Then, when we look at the cytotoxic T-cell mediated disorders, I think the major areas of advance are going to be in better understanding the immunophenotype of cytotoxic T-cell mediated diseases, and then the potential development of tolerization strategies using the specific targets, those specific epitope targets that are involved in paraneoplastic and nonparaneoplastic diseases, and seeing if we can vaccinate patients, but move that immune response into more of a tolerogenic immune response rather than a cytotoxic killing response. And then I think, lastly, we're going to see a dramatic revolution in CAR-T therapeutic approaches to these types of disorders moving forward - and not just, you know, CAR-T therapies that are targeting, you know, CD19 or CD20, but CAR-Ts that are actually personalized and developed so that they can target the specific B- and T-cells in an individual patient and actually do a very fine removal of that autoimmune pathologic process that I think would have significant benefit for patients not only in stopping progression, but also in significantly reducing the potential of side effects - so, a much more targeted approach. So, that's where I think the next ten years is going to be. I think it's very exciting. It's going to require the collaboration of neurologists with, you know, immunologists, hematologists, you know, across the board. So, a very exciting future, I think, for this field.    Dr Berkowitz: Exciting, indeed. And we have learned so much from you and your colleagues at the Mayo Clinic about these conditions, and I definitely encourage our listeners to read your article on this phenomenal issue that really gives us a modern, up-to-date overview of this field and what's coming down the pipeline. So, a real honor to get to speak with you, pick your brain about some of the clinical elements, pitfalls and challenges, and also hear about some of the exciting signs. Thank you so much, Dr Pittock, for joining me today on Continuum Audio.   Dr Pittock: Thank you very much.    Dr Berkowitz: Again, today, I've been interviewing Dr Sean Pittock, whose article with Dr Andrew McKeon on an introduction to autoimmune neurology and diagnostic approach appears in the most recent issue of Continuum on autoimmune neurology. Be sure to check out Continuum Audio episodes from this and other issues. And thank you so much to our listeners for joining us 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 344: Neurology VMR – bilateral lower limb weakness Episode description: We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Aye presents a case of bilateral lower limb weakness to Valeria. Neurology DDx Schema Aye Chan Moe Thant Aye graduated from University of Medicine, Mandalay, Myanmar, and has been… Read More »Episode 344: Neurology VMR – bilateral lower limb weakness

Neurologic infections become emergencies when they lead to a rapid decline in a patient's function; however, neurologic infections are often challenging to recognize. In this episode, Aaron Berkowitz, MD, PhD, FAAN, speaks with Alexandra S. Reynolds, MD, author of the article “Neuroinfectious Emergencies,” in the Continuum® June 2024 Neurocritical Care issue. Dr. Berkowitz is a Continuum® Audio interviewer and professor of neurology at the University of California San Francisco, Department of Neurology and a neurohospitalist, general neurologist, and a clinician educator at the San Francisco VA Medical Center and San Francisco General Hospital in San Francisco, California. Dr. Reynolds is an associate professor in the departments of neurosurgery and neurology at Icahn School of Medicine at Mount Sinai Health System in New York, New York. Additional Resources Read the article: Neuroinfectious Emergencies Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Transcript Full 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, 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 can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. AAN members, stay tuned after the episode to hear how you can get CME for listening.     Dr Berkowitz: This is Dr Aaron Berkowitz, and today, I'm interviewing Dr Alexandra Reynolds about her article on neuroinfectious emergencies, which is part of the June 2024 Continuum issue on neurocritical care. Welcome to the podcast, Dr Reynolds. Um, would you mind, please, introducing yourself to our audience?   Dr Reynolds: Sure. Thank you for the invitation. I'm Alex Reynolds, and I am a neurointensivist at Mount Sinai Hospital in New York City.   Dr Berkowitz: Fantastic. Thanks for joining us. Dr Reynolds has written a really comprehensive article with lots of clinical pearls for the evaluation of patients with neurologic infections. So, to start off, when should we consider a neurologic infection as the cause of a patient's neurologic symptoms?   Dr Reynolds: That is a, really, much more complicated question than I think you recognize. I feel like a lot of it has to do with the risk factors of the patient. So, certainly, you know, a lot of times, we think about a patient who comes in with fever and altered mental status, and that's sort of the patient we're thinking about as having an intracranial infection – but, I do think there are a lot of risk factors that, sort of, may push us in that direction even if the patient doesn't have a fever or even if the patient doesn't seem like meningitis (for example). So, you know, a lot of patients nowadays are immunosuppressed, either because of infections or because of the therapies that we're using as immunosuppressants (so, autoimmune diseases, transplants, bone marrow patients). And then, I think, any patient who has had an intracranial procedure or a spinal procedure, we sort of just have to have in the back of our mind that surgical procedures come, by definition, with risk of infection (and so, that's always something to think about). And then, certainly, anything in terms of endemic risk factors (so a patient who has come from a country that has an endemic infection), we need to just be a little bit more broad about what we're thinking about in that patient population.   Dr Berkowitz: That's very helpful. You mentioned something I wanted to pick up on. We always think fever, of course we're going to be thinking about a neurologic infection, but some types of neurologic infections and in some patient populations, it's possible to have an infection of the nervous system with no fever, sometimes even no white count. What other clues should be considered, or when would you think about pursuing infection even in patients who don't have a fever or an elevated white count?   Dr Reynolds: So, certainly, in patients who have imaging that's a little abnormal. I think, oftentimes, the patients that I've seen with sort of indolent infections have a subdural collection that just doesn't look quite right or doesn't make sense with the clinical history (you know, you can have P. acnes infections that go on for months that people really don't necessarily notice) - so any imaging, oftentimes on MRI, you'll see, sort of, diffusion restriction where you don't really expect to see it. So, those sorts of patients might be ones where if the story is just not really fitting, you might want to think about infection. So, I think it's also important to remember that patients who have procedures elsewhere in the body can sort of seed themselves, and either by direct spread or by hematogenous spread, those infections can kind of seed the CNS - so, patients with valve procedures in the heart, patients who have intraabdominal procedures, there really is no reason that those infections can't travel to the CNS as well. And so, I was sort of always taught, you know, if the story doesn't make sense, then you have to consider infection, even if the patient doesn't have a white count or fever. So, I think just having, sort of, that suspicion in the back of your mind that if you can't really make sense of the story, then consider an infection.   Dr Berkowitz: Yeah. So, obviously, fever, white count, those would clue us in that a patient with new neurologic symptoms (signs) may have an infection as a cause. But, as you said, they may not be present in patients who have had any type of neurosurgical procedure (or you've just taught us even non-neurosurgical procedures elsewhere in the body) that could have led to bacteremia. And then, you mentioned earlier, also patients who are immunocompromised may develop a neurologic infection without fever or white count, and our threshold is certainly lower to pursue that possibility in that population as well. Other points on that before we move on?   Dr Reynolds: I had an attending that told me if you're thinking about a lumbar puncture, you better just do it – so, I think those are wise words to sort of live by. If you're thinking about an infection, you better just work it up.   Dr Berkowitz: Yeah. I think that's right. I heard something similar that if you're standing around on rounds debating whether the patient should get a lumbar puncture, probably, if you've talked about it that much, you should probably do it. I think we've heard the same things in different places. Along those lines of who needs a lumbar puncture, many patients with systemic infections can develop a headache, even if it's just from systemic infection (you don't necessarily have meningitis and cephalitis), and many patients, particularly older patients, develop confusion in the course of systemic infections, like pneumonia and urinary tract infections. And as neurologists, we are often consulted on these patients because they are confused, they are febrile, they may have an elevated white count, and people start to wonder, Could this patient have meningitis? Could this patient have encephalitis? In many cases, at least in my experience (I'm curious to hear your experience), it turns out that these patients have a systemic infection and the confusion and/or headache are related to that systemic infection, not a primary neurologic infection - but based on that topic we just discussed about, if you've talked about lumbar puncture enough, probably best to do it. How do you think about these patients who are, for example, admitted to a medical service for fever and confusion, may or may not have had a systemic source identified, but the suspicion is there? How do you think about which of those patients need a lumbar puncture, or what clues you into thinking to have a higher concern for meningitis, encephalitis, abscess, other neurologic infections in this context?   Dr Reynolds: It's such a good question, because I think, especially as we get older, you know, even things like nuchal rigidity might be hard to assess in a patient who's sort of started to fuse their spine - so, I think it can be really challenging. I think, you know, always go back to basics. Is there any new laterality that doesn't really make sense? Is there a sort of disconnect between imaging and how the patient looks? And it can be so confounded, because these are patients who are also on antibiotics (which themselves can be neurotoxic), and so, it can be really hard to sort of parse that out. But, I do think that there are some less invasive things you can try to do first to sort of help risk stratify your patient. So, you know, certainly, getting a CAT scan and just making sure that everything looks as you would expect it to look - there's no, sort of, hydro out of proportion to what you might expect. I've definitely seen patients who have meningitis that we caught because they have just a little bit of pus in the ventricles that was interpreted as intraventricular hemorrhage. And you sort of just have to sit there and think, like, Does that make sense, or is it an infection? EEG can be helpful, too, if it's lateralizing. You know, I think we don't think as much about HSV in the hospital. But, certainly, if you have something lateralizing on your EEG that just doesn't make sense, I think that could sort of push you in that direction as well. But, again, I think in most cases, unless the patient's very thrombocytopenic or coagulopathic, the risk of an LP sort of doesn't really outweigh the benefit of feeling confident that you haven't missed something, because I think, you know, one of the big points of this article is that if you catch these CNS infections early, people can actually do really well, and, really, most of the morbidity and mortality is from missing the infection - so we've been trying to move away from LP-ing everybody on admission, but I do think that you should be tapping some people that are not infected, because then you're probably catching everyone who is.   Dr Berkowitz: It's great to hear your approach, and I think that aligns with my thinking as well. I do want to ask as a follow-up to that question (I've asked this of internists I work with and other neurologists) - I totally agree with everything you said in the sense that, you know, we are consulted by our internists, we presume that they haven't found a reason that the patient is febrile and confused from a systemic standpoint, and that's why we're being consulted. There are, obviously, many patients who are febrile and confused in the hospital where neurology has not been called because there's other obvious reasons, as you have mentioned. However, as you said, if the patient has some immunocompromise, maybe there's some features that are suggestive in the history or nuchal rigidity - as you said, harder in older patients - but there's something there that you sort of think, maybe we should just do a lumbar puncture just to make sure we sort of settle this because we keep thinking about it. The question is, in your experience, when you've gotten a lumbar puncture more as a rule-out, or you think, I think this is the patient's pneumonia and they're confused because they're delirious in the hospital (sort of toxic metabolic encephalopathy), have you ever been surprised? Talking to an internist colleague, I've said, I feel like I haven't actually seen that much bacterial meningitis in the U.S., fortunately, thanks to vaccination. And, usually, the patient is coming in with a pretty profound syndrome of meningitis or encephalitis. But, as far as patients in the hospital with a fever, where you're thinking, "This is kind of a rule-out, so just make sure, even though I don't think I'm going to find meningitis in a patient who is immunocompetent”, have you ever been surprised and found meningitis encephalitis when you didn't expect to find it? Or, what's been your experience when you, as you said, tap these patients because you'd rather get a few normal ones in there to make sure you never missed the abnormal?   Dr Reynolds: I would say the few times that I've been surprised were not with fully immunocompetent patients. You know, someone with a splenectomy who otherwise looks immunocompetent, someone with pretty advanced cancer - those are examples where you wouldn't necessarily have thought about it as being immunocompromised, but they are. Certainly, I think patients with advanced cancer can, really - they're much higher risk than I used to think about. The more I've taken care of them, the more I've realized how sensitive they are to infections and how quickly that can spread, even if they're not actively getting chemotherapy. But, I would say in general, for the truly immunocompetent patient, I would say I haven't really diagnosed anything super exciting.   Dr Berkowitz: Yeah, that's good to hear. I love to, on these Continuum Audio interviews, poll experts in other institutions who trained other places and, you know, learn from different patient populations if your experience resonates with mine and others I've spoken to. Yeah, that sounds similar to my experience as well, yeah, if the patient is immunocompromised - and as you said, we maybe need to broaden that from being truly profoundly immunocompromised by congenital immunodeficiency or HIV or immunomodulatory therapy to have a slightly broader perspective on what could constitute immunocompromise - and, of course, we'd have an extremely low threshold to perform a lumbar puncture in such patients, as you said. You reminded me of a case I was trying to remember the details (which I don't) – it was a patient, actually, with a temporal lobe glioblastoma that had been resected and had some recurrence and was worsening, and it looked like it was tumor recurrence/progression. And I don't - wasn't my patient, I just sort of heard about it - but I don't know which attending or resident or fellow decided that the patient should get a lumbar puncture, and the patient actually developed HSV encephalitis of the temporal lobe, where the glioblastoma was.   Dr Reynolds: Wow.   Dr Berkowitz: Patients with cancer, especially with all the new immunotherapies - and even without them, as you said - this is a state in which people may be vulnerable to infections and ones you might not immediately think of. So, those are some great pearls. Speaking of pearls, you have a really fantastic section in your article on neurologic complications of CNS infections. In other words, you've already diagnosed the meningitis, encephalitis, abscess, or otherwise, and all the other neurologic complications that can occur in the course of this illness. So, it'd be great to talk with you a little bit about that here. So, if a patient is diagnosed with infectious meningitis or encephalitis (we've made that diagnosis by the clinical picture, the lumbar puncture findings, and/or the neuroimaging), we're following them along, we think we have them on appropriate therapy, (antimicrobial therapy), and their neurologic status worsens - what's the differential diagnosis for this worsening? What are some things we can think about? How do we look for them on exam? How do we work them up?   Dr Reynolds: Yeah. It's funny, because, you know, the topic of this is neuroinfectious emergencies, and when I first heard about it, I was like, “Every neuroinfection is an emergency”, and I think part of the reason I felt that way is because as a neuro ICU physician, I see the complications a lot more. You know, I think, from a meningitis and encephalitis standpoint, certainly cerebral edema (whether it be focal or global) is sort of your biggest concern. If you've used your adjunctive steroid therapy at the beginning before you've started antibiotics, you know the idea is that might help – and, certainly, it should help with potential hearing loss as a result of meningitis - but I would say cerebral edema or development of abscesses because of delayed antibiotic initiation is certainly a concern. If a patient's getting lethargic, hydrocephalus can often be a concern - and that may be obstructive hydrocephalus or communicating hydrocephalus – either way, that is a situation where, really, the patient may need, depending on the etiology of the hydrocephalus, either another lumbar puncture (for example, in the case of cryptococcal meningitis) or an external ventricular drain placement (which would bring them to the ICU in cases where there is an obstructive component). So, I do think hydrocephalus is hard to diagnose. My go-to is to sort of check tone in the legs every day, because a lot of times, patients with developing hydro will start to have really high tone in their legs - so, that's sort of my go-to physical exam finding, although, obviously, hydrocephalus can present as just sort of generalized lethargy or even, you know, worsening nausea and vomiting, for example. And then, I think, you know, if someone starts to be localizing on exam, I think that can be concerning not only for abscess, but potentially for ischemic stroke related to a vasculopathy, for example, or hemorrhage in the context of mycotic aneurysm formation, for example - and, so, I do think there is a role, if a patient starts to become lateralizing, for emergent imaging. And generally, we should be able to see most of the stuff on just a plain CAT scan to start. You know, certainly, localizing stuff can also be as a result of seizures, but I think that that's sort of a diagnosis of exclusion, and rapidly imaging a patient with new focal signs is probably the way to go before putting them on EEG.   Dr Berkowitz: Very helpful pearls. So, um, shifting gears a little bit, right before we began our conversation, you were telling me you had done some work in Malawi, and you were reflecting on some of the differences in epidemiology of neuroinfectious disease and resources available to diagnose neuroinfectious disease. So, I'm sure it would be very interesting for our listeners to hear a little bit about the perspective you bring to the diagnosis and treatment of patients with neurologic infections from your experience in Malawi.   Dr Reynolds: Yeah. So, I was lucky enough as a trainee to be able to go to Malawi for a few weeks with my neuroinfectious disease attending, and I think that it's pretty striking (the difference that we see in lower income countries, compared to the U.S.). I think a lot of the disease processes that we sort of take for granted as being easily treatable are not necessarily easily treatable, not only because of lack of access to medications and antibiotics, but also because of sort of a stigma that might be associated with the workup. So, for example, a lot of people were very hesitant to consent to lumbar puncture, because they had seen that their friends and family members who had gotten lumbar punctures ultimately died, and it didn't seem necessarily clear that the reason that they had died was from the primary infection itself. So, I think that really being attuned to disparities not only abroad, but even - you know, working in New York City, I can say that there are definitely disparities in terms of access to care and health equity, and, certainly, the timing of your presentation almost necessarily will change the outcome, and people who are presenting to the hospital later because of infections that were sort of ignored or because of lack of access to healthcare, those patients, really, by definition, end up doing worse - and so, I think that that is really a big thing to think about in our resource-rich areas, think about these infections.   Dr Berkowitz: Well, thank you for sharing those valuable and important perspectives both from Malawi and from your work in New York City.   Dr Reynolds: Thank you.   Dr Berkowitz: Well, thank you so much, Dr Reynolds, for joining me today on Continuum Audio. I've enjoyed our discussion and learned a lot from it. Again, today, we've been interviewing Dr Alexandra Reynolds, whose article on neuroinfectious emergencies appears in the most recent issue of Continuum on neurocritical care. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to all of our listeners for joining today.   Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, please consider subscribing to the journal. There's a link in the episode notes. We'd also appreciate you following the podcast and rating or reviewing it. AAN members, go to the link in the episode notes and complete the evaluation to get CME for this episode. Thank you for listening to Continuum Audio.

In neurocritical care, the initial evaluation is often fast paced, and assessment and management go hand in hand. History, clinical examination, and workup should be obtained while considering therapeutic implications and the need for lifesaving interventions. In this episode, Aaron Berkowitz, MD, PhD FAAN, speaks with Sarah Wahlster, MD, an author of the article “The Neurocritical Care Examination and Workup,” in the Continuum June 2024 Neurocritical Care issue. Dr. Berkowitz is a Continuum® Audio interviewer and professor of neurology at the University of California San Francisco, Department of Neurology and a neurohospitalist, general neurologist, and a clinician educator at the San Francisco VA Medical Center and San Francisco General Hospital in San Francisco, California. Dr. Wahlster is an associate professor of neurology in the departments of neurology, neurological surgery, and anesthesiology and pain medicine at Harborview Medical Center, University of Washington in Seattle, Washington. Additional Resources Read the article: The Neurocritical Care Examination and Workup Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Guest: @SWahlster Full Episode Transcript Sarah Wahlster, MD   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 can read the full article or listen to verbatim recordings of the article by clicking on the link in the Show Notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the Show Notes. AAN members: stay tuned after the episode to hear how you can get CME for listening.  Dr Berkowitz: This is Dr Aaron Berkowitz, and today I'm interviewing Dr Sarah Wahlster about her article on examination and workup of the neurocritical care patient, which is part of the June 2024 Continuum issue on neurocritical care. Welcome to the podcast, Dr Wahlster. Can you please introduce yourself to the audience? Dr Wahlster: Thank you very much, Aaron. I'm Sarah Wahlster. I'm a neurologist and neurontensivist at Harborview Medical Center at the University of Washington. Dr Berkowitz: Well, Sarah and I know each other for many, many years. Sarah was my senior resident at Mass General and Brigham and Women's Hospital. Actually, Sarah was at my interview dinner for that program, and I remember meeting her and thinking, “If such brilliant, kind, talented people are in this program, I should try to see if I can find my way here so I can learn from them.” So, I learned a lot from Sarah as a resident, I learned a lot from this article, and excited for all of us to learn from Sarah, today, talking about this important topic. So, to start off, let's take a common scenario that we see often. We're called to the emergency room because a patient is found down, unresponsive, and neurology is called to see the patient. So, what's running through your mind? And then, walk us through your approach as you're getting to the bedside and as you're at the bedside. Dr Wahlster: Yeah, absolutely. This was a fun topic to write about because I think this initial kind of mystery of a patient and the initial approach is something that is one of the puzzles in neurology. And I think, especially if you're thinking about an emergency, the tricky part is that the evaluation and management go hand in hand. The thinking I've adapted as a neurointensivist is really thinking about “column A” (what is likely?) and “column B” (what are must-not-miss things?). It's actually something I learned from Steve Greenberg, who was a mutual mentor of us - but he always talked me through that. There's always things at the back of your head that you just want to rule out. I do think you evaluate the patient having in mind, “What are time-sensitive, critical interventions that this patient might need?” And so, I think that is usually my approach. Those things are usually anything with elevated intracranial pressure: Is the patient at risk of herniating imminently and would need a neurosurgical intervention, such as an EVD or decompression? Is there a neurovascular emergency, such as an acute ischemic stroke, a large-vessel occlusion, a subarachnoid hemorrhage that needs emergent intervention? And then other things you think about are seizures, convulsive/nonconvulsive status, CNS infection, spinal cord compression. But I think, just thinking about these pathologies somewhere and then really approaching the patient by just, very quickly, trying to gather as much possible information through a combination of exam and history. Dr Berkowitz: Great. So, you're thinking about all these not-to-miss diagnoses that would be life-threatening for the patient and you're getting to the bedside. So, how do you approach the exam? Often, this is a different scenario than usual, where the patient's not going to be able to give us a history or maybe necessarily even participate in the exam, and yet, as you said, the stakes are high to determine if there are neurologic conditions playing into this patient's status. So, how do you approach a patient at the bedside? Dr Wahlster: So, I think first step in an ICU setting (especially if the patient has a breathing tube) is you think about any confounders (especially sedation or metabolic confounders) - you want to remove as soon as possible, if able. I think as you do the exam, you try to kind of incorporate snippets of the history and really try to see - you know, localize the problem. And also kind of see, you know, what is the time course of the deterioration, what is the time course of the presentation. And that is something I actually learned from you. I know you've always had this framework of “what is it, where is it?” But I think in terms of just a clinical exam, I would look at localizing signs. I think, in the absence of being able to do the full head-to-toe neuro exam and interact with the patient, you really try to look at the brainstem findings. I always look at the eyes right away and look at, I think, just things like, you know, the gaze (how is it aligned? is there deviation? is there a skew? what do the pupils look like? [pupillary reactivity]). I think that's usually often a first step - that I just look at the patient's eyes. I think other objective findings, such as brainstem reflexes and motor responses, are also helpful. And then you just look whether there's any kind of focality in terms of - you know, is there any difference in size? But I think those are kind of the imminent things I look at quickly. Dr Berkowitz: Fantastic. Most of the time, this evaluation is happening kind of en route to the CT scanner or maybe a CT has already happened. So, let's say you're seeing a patient who's found down, the CT has either happened or you asked for it to happen somewhat quickly after you've done your exam, and let's say it's not particularly revealing early on. What are the sort things on your exam that would then push you to think about an MRI, a lumbar puncture, an EEG? You and I both spend time in large community hospitals, right, where “found down” is one of the most common chief concerns. In many cases, there isn't something to see on the CT or something obvious in the initial labs, and the question always comes up, “Who gets an MRI? Who gets an LP? Who gets an EEG?” - and I'm not sure I have a great framework for this. Obviously, you see focality on your exam, you know you need to look further. But, any factors in the history or exam that, even with a normal CT, raise your suspicion that you need to go further? Dr Wahlster: It's always a challenge, especially at a community hospital, because some of these patients come in at 1 AM where the EEG is not imminently available. But I think - let's say the CT scan is absolutely normal and doesn't give me a cause, but as an acute concerning deterioration, I think both EEG and LP would cross my mind. MRI I kind of see a little bit as a second-day test. I think there's very rare situation where an acute MRI would inform my imminent management. It's very informative, right, because you can see very small-vessel strokes. We had this patient that actually had this really bad vasculitis and we were able to see the small strokes everywhere on the MRI the day later, or sometimes helps you visualize acute brainstem pathology. But I think, even that - if you rule out a large-vessel occlusion on your CTA, there's brainstem pathology that is not imminently visible on the CT - it's nothing you need to go after. So, I do think the CT is a critical part of that initial eval, and whereas I always admire the neurological subspecialties, such as movements, where you just – like, your exam is everything. I think, to determine these acute time-sensitive interventions, the CT is key. And also, seeing a normal CT makes me a little less worried. You always look at these “four H” (they're big hypodensity, hyperdensity, any shift; is there hydrocephalus or herniation). I think if I don't have an explanation, my mind would imminently jump to seizure or CNS infection, or sometimes both. And I think then I would really kind of - to guide those decisions and whether I want to call in the EEG tech at 2 AM - I would, you know, again, look at the history and exam, see if there's any gaze deviation, tongue biting, incontinence - anything leading up towards seizure. I think, though, even if I didn't have any of those, those would strengthen my suspicion. If I really, absolutely don't have an explanation and the patient off sedation is just absolutely altered, I would still advocate for an EEG and maybe, in the meantime, do a small treatment trial. And I think with CNS infection - obviously, there are patients that are high risk for it - I would try to go back and get history about prodromes and, you know, look at things like the white count, fevers, and all of that. But again, I think if there's such a profound alteration in neurologic exam, there's nothing in the CT, and there's no other explanation, I would tend to do these things up front because, again, you don't want to miss them. Dr Berkowitz: Yeah, perfect. So many pearls in there, but one I just want to highlight because I'm not sure I've heard the mnemonic - can you tell us the four Hs again of sort of neurologic emergencies on CT? Dr Wahlster: Yeah. So, it's funny; for ages - I'm actually not sure where that's coming from, and I learned it from one of my fellows, one of our neurocritical care fellows - he's a fantastic teacher and he would teach our EM and anesthesia residents about it and his approach to CT. But yeah, the four H - he was always kind of like, “Look at the CT. Do you see any acute hypodensities, any hyperdensities?” And hypodensities would be involving infarct or edema; hyperdensities would be, most likely, hemorrhage (sometimes calcification or other things). Then, “Do you see hydrocephalus?” (because that needs an intervention). And, “Look at the midline structures and the ventricles.” And then, “Do you see any signs of herniation?” And he would go through the different types of herniation. But I thought that's a very good framework for looking at the “noncon” and just identifying critical pathology that needs some intervention. Dr Berkowitz: Yeah – so, hypodensity, hyperdensity, herniation, hydrocephalus. That's a good one – the four Hs; fantastic. Okay. So, a point that comes up a few times in your article - which I thought was very helpful to walk through and I'd love to pick your brain about a little bit – is, which patients need to be intubated for a neurologic indication? So, often we do consultations in medical, surgical ICUs; patients are intubated for medical respiratory reasons, but sometimes patients are intubated for neurologic reasons. So, can you walk us through your thinking on how to decide who needs to be intubated for the concern of depressed level of consciousness? Dr. Wahlster: It's an excellent question, and I think I would bet there's a lot of variation in practice and difference in opinion. There was actually the 2020 ESICM guidelines kind of commented on it, and those are great guidelines in terms of just intubation, mechanical ventilation of patients, and just acknowledging how there is a lack of really strong evidence. I would say the typical mantra (“GCS 8, intubate”) has been proposed in the trauma literature. And at some point, I actually dug into this to look behind the evidence, and there's actually not as much evidence as it's been put forth in guidelines and that kind of surprised me - that was just recently. I was like, “Actually, let me look this up.” I would say I didn't find a ton of strong evidence for it. I would say, as neurologist – you know, I'm amazed because GCS, I think is a - in some ways, a good tool to track things because it's so widely used across the board. But I would say, as neurologists, we all know that it sometimes doesn't account for some sort of nuances; you know, if a patient is aphasic, if a patient has an eyelid-opening apraxia - it can always be a little confounded. I'm amazed that GCS is still so widely used, to be frank. But I would say there is some literature - some school of thought - that maybe just blindly going by that mantra could be harmful or could not be ideal. I would say – I mean, I look at the two kind of functional things: oxygenation and ventilation. I think, in a neuro patient, you always think about airway protection or the decreased level of consciousness being a major issue (What is truly airway protection? Probably a mix of things). Then there's the issue of respiratory centers and respiratory drive - I think those are two issues you think about. But ultimately, if it leads to insufficient oxygenation - hypoxia early on is bad and that's been shown in several neurologic acute brain injuries. I think you also want to think about ventilation, especially if the mental status is poor to the point that the PCO2 elevates, that could also augment an ICP or exacerbate an ICP crisis. Or sometimes, I think there's just dysregulation of ventilation and there's hyperventilation to the point that the PCO2 is so low that I worry about cerebral vasoconstriction. So, I worry about these markers. I think, the oxygenation, I usually just kind of initially track on the sats. Sometimes, if the patient is profoundly altered, I do look at an arterial blood gas. And then there are things like breathing sounds (stridor, stertor [the work of breathing]). And I think something that also makes me have a lower threshold to intubate is if I'm worried and I want to scan, and I'm worried that the patient can't tolerate it - I want an imminent scan to just see why the patient is altered, or seizing, or presenting a certain way. Dr Berkowitz: All great pearls for how to think through this. Yeah - it's hard to think of hard and fast rules, and you can get to eight on the GCS in many different ways, as you said, some of which may not involve the respiratory mechanics at all. So, that's a helpful way of thinking about it that involves both the mental state, kind of the tracheal apparatus and how it's being managed by the neurologic system, and also the oxygen and carbon dioxide (sort of, respiratory parameters) – so, linking all those together; that's very helpful. And, related question – so, that's sort of for that patient with central nervous system pathology, who we're thinking about whether they need to be intubated for a primary neurologic indication. What about from the acute neuromuscular perspective (so, patients with Guillain-Barré syndrome or myasthenic crisis); how do you think about when to intubate those patients? Dr Wahlster: Yeah, absolutely - I think that's a really important one. And I think especially in a patient that is rapidly progressing, you always kind of think about that, and you want them in a supervised setting, either the ER or the ICU. I mean, there's some scores - I think there's the EGRIS score; there's some kind of models that predict it. I would say, the factors within that model, and based on my experience, often the pace of progression of reflex motor syndrome. I often see things like, kind of, changes in voice. You know, myasthenia, you look at things like head extension, flexion - those are the kind of factors. I would say there's this “20/30/40 rule” about various measures of, like, NIF and vital capacities, which is great. I would say in practice, I sometimes see that sometimes the participation in how the NIF is obtained is a little bit funky, so I wouldn't always blindly go by these numbers but sometimes it's helpful to track them. If you get a reliable kind of sixty and suddenly it drops to twenty, that makes me very concerned. But I would say, in general, it's really a little bit the work of breathing - looking at how the patient looks like. There's also (at some point) ABG abnormalities, but we always say, once those happen, you're kind of later in the game, so you should really - I think anyone that is in respiratory distress, you should think about it and have a low threshold to do it, and, at a minimum, monitor very closely. Dr Berkowitz: Yeah, we have those numbers, but so often, our patients who are weak, from a neuromuscular perspective, often have facial and other bulbar weakness and can't make a seal on the device that is used to check these numbers, and it can look very concerning when the patient may not, or can be a little bit difficult to interpret. So, I appreciate you giving us sort of the protocol and then the pearls of the caveats of how to interpret them and going sort of back to basics. So, just looking at the patient at the bedside and how hard they are working to breathe, or how difficult it is for them to clear their secretions from bulbar weakness. Moving on to another topic, you have a really wonderful section in your article on detecting clinical deterioration in patients in the neuro ICU. Many patients in the neuro ICU - for example, due to head trauma or large ischemic stroke or intracerebral hemorrhage, subarachnoid hemorrhage, or status epilepticus - they can't communicate with us to tell us something is getting worse, and they can't (in many cases) participate in the examination. They may be intubated, as you said, sedated or maybe even not sedated, and there's not necessarily much to follow on the exam to begin with if the GCS is very low. So, I'd love to hear your thoughts and your pearls, as someone who rounds in the neuro-ICU almost every day. What are you looking for at the bedside to try to detect sort of covert deterioration, if you will, in patients who already have major neurologic deficits, major neurologic injury or disease that we're aware of? I'm trying to see if there is some type of difference at the bedside that would lead you to be concerned for some underlying change and go back to the scanner or repeat EEG, LP, et cetera. Dr Wahlster: Yeah. I think that's an excellent question because that's a lot of what we do in the neuro ICU, right? And when you read your Clans, your residency, like, “Ah, QNR neuro checks, [IG1]  ” right? We often do that in many patients. But I think in the right patient, it can really be life or death a matter, and it is the exam that really then drives a whole cascade of changes in management and detects the need for lifesaving procedure. I would say it depends very much on the process and what you anticipate, right? If you have, for example, someone with a large ischemic stroke, large MCA stroke, especially, right, then there's sometimes conversations about doing a surgical procedure before they herniate. But let's say, kind of watch them and are worried that they will, you do worry about uncal herniation, and you pay attention to the pupil, because often, if the inferior division is infarcted, you know, you can see that kind of temporal tickling the uncus already. And so, I think those are patients that I torture with those NPi checks and checking the pupil very vigilantly. I would say, if it's a cerebellar stroke, for example, right, then you think about, you know, hydrocephalus. And often patients with cerebellar stroke - you know, the beauty of it is that if you detect it early, those patients can do so well, but they can die, and will die if they develop hydrocephalus start swelling. But I think, often something I always like to teach trainees is looking at the eye movements in upgaze and downgaze because, often, as the aqueduct, the third ventricle gets compressed and there's pressure on the colliculi – you kind of see vertical gaze get worse. But I would say I think it's always good to know what the process is and then what deterioration would look like. For example, in subarachnoid hemorrhage, where you talk about vasospasm - it's funny - I think a really good, experienced nurse is actually the best tool in this, but they will sometimes come to you and say, “I see this flavor,” and it's actually a constellation of symptoms, especially in the anterior ACA (ACom) aneurysms. You sometimes see patients suddenly, like, making funky jokes or saying really weird things. And then you see that in combination with, sometimes, a sodium drop, a little bit of subfebrile temperature; blood pressure shoot up sometimes, and that is a way the brain is sometimes regulating. But it's often a constellation of things, and I think it depends a little on the process that you're worried about. Dr Berkowitz: Yeah, that's very helpful. You just gave us some pearls for detecting deterioration related to vasospasm and subarachnoid hemorrhage; some pearls for detecting malignant edema in an MCA stroke or fourth ventricular compression in a large cerebellar stroke. Patients I find often very challenging to get a sense of what's going on and often get scanned over and over and back on EEG, not necessarily find something: patients with large intracerebral hemorrhage (particularly, in my experience, if the thalamus is involved) just can fluctuate a lot, and it's not clear to me actually what the fluctuation is. But you're looking for whether they're developing hydrocephalus from third ventricular compression with a thalamic hemorrhage (probably shouldn't be seizing from the thalamus, but if it's a large hemorrhage and cortical networks are disrupted and it's beyond sort of the subcortical gray matter, or has the hemorrhage expanded or ruptured it into the ventricular system?) And yet, you scan these patients over and over, sometimes, and just see it's the same thalamic hemorrhage and there's some, probably, just fluctuation level of arousal from the thalamic lesion. How do you, as someone who sees a lot of these patients, decide which patients with intracerebral hemorrhage - what are you looking for as far as deterioration? How do you decide who to keep scanning when you're seeing the same fluctuations? I find it so challenging - I'm curious to hear your perspective. Dr Wahlster: Yeah, no - that is a very tricky one. I mean, unfortunately, in patients with deeper hemorrhages or deeper lesions - you know, thalamic or then affecting brainstem - I think those are the ones that ultimately don't have good, consistent airway protection and do end up needing a trach, just because there's so much fluctuation. But I agree - it's so tricky, and I don't think I can give a perfect answer. I would say, a little bit I lean on the imaging. And for example - let's say there's a thalamic hemorrhage. We recently actually had a patient - I was on service last week - we had a thalamic hemorrhage with a fair amount of edema on it that was also kind of pressing on the aqueduct and didn't have a lot of IVH, right? But it was, like, from the outside pushing on it and where we ended up getting more scans. And I have to say, that patient actually just did fine and actually got the drain out and didn't need a shunt or anything, and actually never drained. We put an EVD and actually drained very little. So, I think we're still bad at gauging those. But I think, in general, my index of suspicion or threshold to scan would be lower if there was something, like, you know, a lot of IVH associated, if, you know, just kind of push on the aqueduct. It's very hard to say, I think. Sometimes, as you get to know your patients, you can get a little bit of a flavor of what is within normal fluctuation. I think it's probably true for every patient, right? - that there's always some fluctuation within the realm of like, “that's what he does,” and then there's something more profound. Yeah, sorry - I wish I could give a better answer, but I would say it's very tricky and requires experience and, ideally, you really taking the time to examine the patient yourself (ideally, several times). Sometimes, we see the patient - we get really worried. Or the typical thing we see the ICU is that the neurosurgeons walk around at 5 AM and say, like, “She's altered, she's different, she's changed.” And then the nurse will tell you at 8 AM, like, “No, they woke up and they ate their breakfast.” So, I think really working with your nurse and examining the patient yourself and just getting a flavor for what the realm of fluctuation is. Dr Berkowitz: Yeah - that's helpful to hear how challenging it is, even for a neurocritical care expert. I'm often taking care of these patients when they come out of the ICU and I'm thinking, “Am I scanning these patients too much?” Because I just don't sort of see the initial stage, and then, you know, you realize, “If I'm concerned and this is not fitting, then I should get a CT scan,” and sometimes you can't sort it out of the bedside. So, far from apologizing for your answer, it's reassuring, right, that sometimes you really can't tell at the bedside, as much as we value our exam. And the stakes are quite high if this patient's developed intraventricular hemorrhage or hydrocephalus, and these would change the management. Sometimes you have these patients the first few days in the ICU (for us, when they come out of the ICU) are getting scanned more often than you would like to. But then you get a sense of, “Oh, yeah - these times of day, they're hard to arouse,” or, “They're hard to arouse, but they are arousable this way,” and then, “When they are aroused, this is what they can do, and that's kind of what we saw yesterday.” And yet, as you said, if anyone on the team (the resident, the nurse, the student, our neurosurgery colleague) says, “I don't think this is how they were yesterday,” then, very low threshold to just go back and get a CT and make sure we're not missing something. Dr. Wahlster: Exactly. Yeah. I would say the other thing is also certain time intervals, right? If I'm seeing a patient that may be in vasospasm kind of around the days seven to ten, for the first fourteen day, I would be a little bit more nervous. Or with swelling - acute ischemic stroke says that could peak swelling, when knowing which [IG2]  , I would just be more anxious or have a lower threshold to scan. Yeah. Dr Berkowitz: Yeah - very helpful. Well, thank you so much for joining me today on Continuum Audio. Dr Wahlster: Thank you very much, Aaron. Dr Berkowitz: Again, today we've been interviewing Dr Sarah Wahlster, whose article, “Examination and Workup of the Neurocritical Care Patient” appears in the most recent issue of Continuum, on neurocritical care. Be sure to check out Continuum Audio episodes from this and other issues. And thank you so much to our listeners for joining us 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 practice. And right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024 or use the link in the episode notes to learn more and take advantage of this great discount. This offer ends June 30, 2024. AAN members: go to the link in the episode notes and complete the evaluation to get CME. Thank you for listening to Continuum Audio.

Episode 339: Neurology VMR – left facial numbness for 5 days We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Aye presents a case of left facial numbness for 5 days to Andrea and Sridhara. Neurology DDx Schema Aye Chan Moe Thant Aye graduated from University of Medicine, Mandalay, Myanmar,… Read More »Episode 339: Neurology VMR – left facial numbness for 5 days

New daily persistent headache is a syndrome characterized by the acute onset of a continuous headache in the absence of any alternative cause. Triggers are commonly reported by patients at headache onset and include an infection or stressful life event. In this episode, Aaron Berkowitz, MD, PhD, FAAN, speaks with Matthew Robbins, MD, FAAN, FAHS, author of the article “New Daily Persistent Headache,” in the Continuum® April 2024 Headache issue. Dr. Berkowitz is a Continuum® Audio interviewer and professor of neurology at the University of California San Francisco, Department of Neurology and a neurohospitalist, general neurologist, and a clinician educator at the San Francisco VA Medical Center and San Francisco General Hospital in San Francisco, California. Dr. Robbins is an associate professor of neurology and director of the Neurology Residency Program at New York-Presbyterian/Weill Cornell Medical Center in New York, New York. Additional Resources Read the article: New Daily Persistent Headache Subscribe to Continuum: continpub.com/Spring2024 Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @https://twitter.com/AaronLBerkowitz Guest: @ @mrobbinsmd Full Transcript Available: 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 can read the full article or listen to verbatim recordings of the article by visiting the link in the Show Notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the Show Notes. AAN members: stay tuned after the episode to hear how you can get CME for listening.   Dr Berkowitz: This is Dr Aaron Berkowitz, and today I'm interviewing Dr Matthew Robbins about his article on new daily persistent headache, from the April 2024 Continuum issue on headache. Dr Robbins is an Associate Professor of Neurology and Director of the Neurology Residency Program at New York-Presbyterian/Weill Cornell Medical Center, in New York. Welcome to the podcast. Dr Robbins: It's great to be with you, Dr Berkowitz. Dr Berkowitz: Well, thanks so much for joining us this morning. To start, what is new daily persistent headache? I think it's an entity maybe that might be new to some of our listeners. Dr Robbins: Yeah - it's an entity that also struck me when I was in training. I didn't hear much of it as a neurology trainee until I did a fellowship in headache, where, all of a sudden, we were seeing patients with this syndrome (and labeled as such) all the time. And that actually inspired me to begin a research project to better characterize it - a clinical project that ended up helping to broaden the diagnostic criteria. New daily persistent headache really is just defined by what it says - it's new; it's every day; it persists; it's a headache. It can't be from some other identifiable cause, which includes both secondary disorders (you know, something that, where headache is a symptom of) or a primary headache disorder; distinguishes itself from, say, migraine or tension-type headache because there's no real headache history and there's an abrupt onset of a daily and continuous headache that has to last for at least three months since onset. And the onset is typically remembered - it's usually acute or abrupt; there may or may not be some circumstances that surrounded the onset that might have some diagnostic or causal or associated implications that we can explore. Dr Berkowitz: Okay. So, I always find it challenging in headache medicine and some other areas where we don't have a biomarker, per se - an imaging finding, a lab finding; we have an eloquent and detailed clinical description - to know how comfortable to be making a diagnosis like this. In this case, particularly, right - you said it has to be going on for three months. What if I see a patient one month into something I think could be this, but I can't technically say, per the criteria, right (it's three months)? When do you start thinking about this diagnosis in patients, and what are some of the main considerations in confirming the diagnosis, and what needs to be ruled out or excluded for making the diagnosis?   Dr Robbins: I think traditionally, in headache, the term “chronic” has that three-month time period. The reasons are twofold: one is that, typically, if there's some secondary disorder that might have some distinguishing feature (something that really evokes the headache or some other neurological accompaniment that develops in addition to headache), it would pretty much be likely to declare itself by the three-month mark. Or if it was something that was very self-limited, it would probably go away before three months have elapsed. Or if it resolved after some days or weeks but then declared itself as a more episodic disorder, then we might say someone who begins with continuous headache that might, for example, resemble migraine (maybe it presented a status migrainosis but then it devolved into a more episodic disorder that might just be migraine overall). So, I think that's pretty much why the three-month mark has been so prevalent in the International Classification of Headache Disorders, including how new daily persistent headache is diagnosed. But at the same time, there's lots of disorders that might mimic (or might be misdiagnosed as) new daily persistent headache, and they really are a secondary disorder. Probably the most common one that we think about is a disorder of intracranial pressure or volume, mainly because routine MRI features could be normal or could be easily missed if they had subtle abnormalities. The defining symptom of those disorders are also continuous headache, often from onset, with an abrupt and remembered nature. So, that's often the main category of secondary headache that might be misdiagnosed as primary headache. I think, probably, idiopathic intracranial hypertension as the prototypical disorder of high pressure often declares itself with visual symptoms, pulsatile tinnitus, and other abnormalities. And nowadays, there's much more increasing recognition for MRI abnormalities or even MRV abnormalities with such patients. But spontaneous intracranial hypotension (despite increasing recognition of CSF leaks in the spine that lead to intracranial hypotension or hypovolemia) really remains an underdiagnosed entity. I think that's one disorder where - for example, if I'm seeing a patient with new daily persistent headache and there's no orthostatic or positional nature to their headache - I will still do an MRI, with and without contrast, to be sure. But that the chances of them having a spontaneous CSF leak are low if that scan is unremarkable. Dr Berkowitz: That's very helpful. Yeah. It's interesting; when you talked about the criteria for this condition - that it has an acute onset, which is a red flag, right, and it is persistent for months, which for a new headache would also be a red flag. So, this is a condition - correct me if I'm wrong – that, if you're considering it, there's no way that you're going to make this diagnosis without neuroimaging because there are two red flags, in a way, embedded in the criteria before we get to the other diagnoses being excluded. Is that right? So, this would only be a diagnosis made clinically but after neuroimaging is obtained, given that two red flags are part of the criteria – isn't that right? Dr Robbins That's absolutely right. So, I can't imagine there's anyone who has new daily persistent headache who hasn't had appropriate neuroimaging, and that typically should include an MRI, with and without contrast, unless there's some compelling reason to avoid that. There's some other workup that could be done that's not universal but - for example, in clinic-based studies of patients who have new daily persistent headache versus those who may have, say, chronic migraine or chronic tension-type headache, you may find more abnormalities. The biggest and more compelling example of that is hypothyroidism, which presumably would be somewhat subclinical if it hadn't been brought to someone's medical attention earlier. It doesn't mean that hypothyroidism is the cause of new daily persistent headache, but it could be some type of triggering or priming factor that leads to headache perpetuation in some patients. Sometimes, if that hasn't been done already, that would be a blood test I might think about sending. And, of course, the context of onset; if someone lived in a place where tick-borne illnesses are endemic, if there are other neurological symptoms, that might prompt looking for serological evidence of Lyme disease, as one example. Dr Berkowitz: We see a lot of headache. I'm a general neurologist; I know you're a headache specialist; we all see a lot of patients with headache. You and I both work closely with residents. Often, residents will come to present a headache patient to me and they'll say, “The patient seems to have a new daily persistent headache. They haven't been imaged yet. They have a completely normal exam. The history fits.” And I always ask them, “Okay, we have to get neuroimaging, right? There's at least one red flag of the chronicity, maybe the red flag of something beginning relatively abruptly. Even though you're looking at the patients - I'm pretty sure that imaging is going to be normal, but we've got to do it.” But I always encourage residents, “Try to predict - do you think the imaging is going to be normal (this is a rule out) or do you think you're going to see something (this is a rule in)? - just to sort of work on calibrating your clinical judgment.” I'd love to ask you - as a headache specialist, when you're looking at the patient and say, “I know I need to get neuroimaging here to fully make this diagnosis of exclusion,” or you've heard something that sounds like a red flag; you know you're obligated to image, but your clinical suspicion of finding anything more than something incidental is pretty low. How often are you surprised in practice in a sort of enriched tertiary headache population? Dr Robbins: That's a great way to frame such a presentation on how a resident would present to you the case and whether it's a rule in or rule out. I totally agree with your approach. I think much of it depends on the clinical story. I think if it was just a spontaneous onset of headache that kind of resembles migraine that just continued, then likely the MRI is being done to just be sure we're not missing anything else. However, if the headache started – really, say someone coughed vigorously or bent over and the headache started, and there was some clear change that you could perceive in - that was, say, the Valsalva or a transiently raised intracranial pressure, or some other maneuver; then you might really say, “Well, this really could be a spontaneous CSF leak,” for example. Even if the MRI of the brain, with and without contrast, is totally normal, I'm not really sure I'm convinced - that you might even take it further. For example, you might do an MRI of the total spine, with a CSF-leak-type protocol, to see if there's some sign of a spontaneous CSF leak or an extradural collection. So, I think in the cases where the preclinical suspicion is higher for a secondary headache, it might not stop at an MRI of the brain (with and without contrast) that's normal. Patients with spontaneous CSF leaks - about eighty percent of them have abnormal brain MRIs, but twenty percent don't. We found, from some observational studies, that a newer cause of intracranial hypotension, such as a CSF venous fistula in the spine, is more likely to present than other causes of CSF leak - with say, Valsalva-associated headache or cough-associated headache. That might prompt us to really take a workup more deeply into that territory, rather than someone where it really just sounds like chronic migraine that switched on. And maybe in those patients, when you dig around, they were carsick as a kid, or they were colicky babies, or they used to get stomachaches and missed school as a teenager here and there, and you think migraine biology is at play. Dr Berkowitz: So, if you're thinking of this diagnosis before you can make it, these patients are going to get an MRI, with and without contrast. And it sounds like the main things you're looking to make sure you're not missing are idiopathic intracranial hypertension or intracranial hypotension from some type of leak. Any other secondary headaches you worry about potentially missing in these patients or want to rule out with any particular testing? Dr Robbins: Yeah - I think sometimes we think of other vascular disorders, especially - when these patients come to medical attention, it's often a total change from what they're used to experiencing. They may present to the emergency room. So, it depends on the circumstance. You might need to rule out cerebral venous thrombosis. Or if there was a very abrupt onset or a relapsing nature of abrupt-onset headaches with sort of interictal persistent headache, we might think of other arteriopathies, such as reversible cerebral vasoconstriction syndrome. There's the more common things to rule out - or commonly identified conditions to rule out - like neoplasm and maybe a Chiari malformation in certain circumstances; those usually would declare themselves pretty easily and obviously on scan or even on clinical exam. Dr Berkowitz: Another question I'd love to ask you as a headache specialist, in your population - sometimes we see this type of new daily persistent headache presentation in older patients, and the teaching is always to rule out giant cell arteritis with an ESR and CRP, in the sense that older patients can present with just headache. Again, my clinical experience as a general neurologist - I wanted to ask you as a headache specialist – is, for the countless times I've done this (older patient has gotten their neuroimaging; we've gotten ESR and CRP), I've never made a diagnosis of giant cell arteritis based on a headache alone, without jaw claudication, scalp tenderness, visual symptoms or signs. Have you picked this up just based on a new headache, older person, ESR, CRP? I'm going to keep doing it either way, but just curious - your experience. Dr. Robbins: Yeah. We're taught in the textbooks (I'm sure we're taught by past Continuum issues and maybe even in this very issue) about that dictum that's classically in neurology teaching. But I agree - I've never really seen pure daily headache from onset, without any other accompaniments, to end up being giant cell arteritis. Then again, someone like that might walk in tomorrow, and the epidemiology of giant cell arteritis supports doing that in people over the age of fifty. But almost always, it's not the answer; I totally agree with you. Dr Berkowitz: Good to compare notes on that one. Okay - so let's say you're considering this diagnosis. You've gotten your neuroimaging, you've gotten (if the patient is over fifty) your ESR and CRP, and you ruled out any dangerous secondary causes here. You have a nice discussion in your article about the primary headache differential diagnosis here. So, now we're sort of really getting into pure clinical reasoning, right, where we're looking at descriptions (colleagues like yourself and your colleagues have come up with these descriptions in the International Classification of Headache Disorders). Here again, we're in a “biomarker-free zone,” right? We're really going on the history alone. What are some of the other primary headache disorders that would be management changing here, were you to make a diagnosis of a separate primary headache disorder, as compared to new daily persistent headache? Dr Robbins: I think the two main disorders really are chronic migraine and chronic tension-type headache. Now, what we're taught about chronic migraine and chronic tension-type headache is that they are disorders that begin in their episodic counterparts (episodic migraine, episodic tension-type headache) and then they evolve, over time, to reach or culminate in this daily and continuous headache pattern, typically in the presence of risk factors for that epidemiologic shift we know to exist but that may happen on the individual level, which does include things that we can't modify, like increasing age, women more than men, some social determinants of health (like low socioeconomic status), a head injury (even if it didn't cause a concussion or clear TBI), a stressful life event, medication overuse, having comorbid psychiatric or pain disorders in addition to the headache problem, having sleep apnea that's untreated, and so on. New daily persistent headache - by definition, it should really be kind of “switched on.” Many years ago, Dr Bill Young and Dr. Jerry Swanson wrote an editorial where they labeled new daily persistent headache as the “switched-on headache.” Then, we're taught in headache pathophysiology that this chronification process happens over time because of, perhaps, markers of central sensitization that might clinically express itself as allodynia in trigeminal or extratrigeminal distributions. So, we're not comfortable with this new daily persistent headache, where we think the biology is like chronic migraine that gets switched on abruptly, but in so many patients, it seems to be so - it behaves like chronic migraine otherwise; the comorbidities might be the same; the treatments might still work similarly for both disorders in parallel. So, I think those are the two that we think about. Obviously, if there's unilateral headache, we might think of a trigeminal autonomic cephalalgia that's continuous, even if it doesn't have associated autonomic signs like ptosis or rhinorrhea (which is hemicrania continua) - and in those patients, we would think about a trial of indomethacin. But otherwise, I think chronic migraine and chronic tension-type headache are the two that phenotypically can look like new daily persistent headache. In patients with new daily persistent headache, about half have migraine-type features and about half have tension-type features. When I was a fellow, the International Headache Society and the classification only allowed for those who have more tension-type features to be diagnosed as new daily persistent headache. But we (and many other groups) have found that migraine-type features are very common in people who fulfill rigorously the criteria for new daily persistent headache otherwise. And then the latest iteration of the classification has allowed for us to apply that diagnosis to those with migraine features. Dr Berkowitz: That's very helpful. So, we've ruled out secondary causes and now you're really trying to get into the nuances of the history to determine, did this truly have its abrupt onset or did it evolve from an episodic migraine or tension-type headache? But it could be described by the patient as migrainous, be described by the patient as having tension features The key characteristics (as you mentioned a few times) should be abrupt onset and a continuous nature. Let's say, now you (by history) zeroed in on this diagnosis of new daily persistent headache. You've ruled out potential secondary causes. You're pretty convinced, based on the history, that this is the appropriate primary headache designation. How do you treat these patients? Dr Robbins: Well, that's a great question, Dr Berkowitz, because there's this notoriety to the syndrome that suggests that patients just don't respond to treatments at all. In clinical practice, I can't dispute that to a degree. I think, in general, people who have this syndrome seem to not respond as well, to those who have clear established primary headache disorders. Part of that might be the biology of the disorder; maybe the disorder is turned on by mechanisms that are different to migraine (even though it resembles chronic migraine) and therefore, the medications we know to work for migraine may not be as effective. In some, it could be other factors. There's just a resistance to appreciating that you have this headache disorder that - one day you were normal, the next day you're afflicted by headache that's continuous. And there's almost this nihilism that, “Nothing will work for me, because it's not fair - there's this injustice that I have this continuous headache problem.” And often people with new daily persistent headache may be resistant to, say, behavioral therapies that often are really helpful for migraine or tension-type headache because of this sort of difficult with adjustment to it. But at least there's observational studies that suggest that most of the treatments that work for migraine work for new daily persistent headache. There's been studies that show that people can respond to triptans. In my clinical experience, CGRP antagonists that work for the acute treatment of migraine may work. There is evidence that many of the traditional, older medicines (like tricyclic antidepressants, topiramate, valproate, beta-blockers, probably candesartan) and others that we use for migraine may work. There's observational studies specifically for new daily persistent headache that show that anti-CGRP therapies in the form of monoclonal antibodies and botulinum toxin can work for the disorder. Are there anything specific for some of the new daily persistent headache that might work? Not that we really know. There's been some attempts to say, “Well, if you get these people in the hospital early and try to reduce the risk of headache persistence by giving them DHE, or dexamethasone, or lidocaine, or ketamine, will you reduce the chances of headache persistence at that three-month mark or longer?” We don't really know (there's some people who believe that, though). Maybe there's good reason to do some type of elective hospitalization for aggressive treatment because we know that, notoriously, the treatment response is very mixed. There's been specific treatments that people have looked at. There's been some anecdotes about doxycycline as a broad anti-inflammatory type of treatment that might be used in a variety of neurological disorders, but there's really nothing in the peer-reviewed literature that suggests that is effective or safe, necessarily. And I think a lot of people in new daily persistent headache do develop a profile that resembles chronic migraine (they can develop medication overuse very easily). Often, goal setting is really important in the counseling of such patients. You really have to suggest that the goal for them might be difficult to have them pain-free at zero and cured, but we want this to be treated so the peaks of severity flatten out a bit, and then the baseline level of pain diminishes so that it devolves into a much more episodic disorder over time that looks like regular migraine or regular tension-type headache. Dr Berkowitz: I see. So, in addition to starting a migraine-type prophylactic agent based on the patient's comorbidities and potential benefits of the medication (the same way we would choose a migraine prophylactic), do you do anything, typically, to try to, quote, “break the cycle” - a quick pulse of steroids as an outpatient or a triptan in the office - and see how they do, or do you typically start a prophylactic agent and go from there? Dr Robbins: I think, like all things, it kind of depends on the distress of the patient and how they are functioning. If it's someone who's just out of work, cannot function - and someone like that might be very amenable to an elective hospitalization or some parenteral therapy, or maybe an earlier threshold to use a preventative treatment than we would be doing otherwise in someone with migraine overall - I think that it really depends on that type of a disability that's apparent early. I think it's compelling that, with new daily persistent headache, about a third of people report some antecedent infection that was around at the time. When new daily persistent headache was first described by this Canadian neurologist, Dr Vanast, in the 1980s, it was described in the context of Epstein-Barr virus infection, or at least a higher rate of serologies that are positive for, perhaps, recent Epstein-Barr exposure. And we know that Epstein-Barr is obviously implicated in lots of neurological diseases, like multiple sclerosis. And I mean, I think about these things all the time, and especially with COVID now. So, it's compelling - as a postinfectious disorder, do we, as neurologists (who are so comfortable with using pulse-dose steroids, IVIG) - do we use these things for a new daily persistent headache? But there's no great evidence that enduring inflammation in the dura that would spill into CSF analyses is really present in such patients. There was one study that looked at markers, such as TNF-alpha, in the CSF, but the rates of seeing that were the same in new daily persistent headache and chronic migraine, so there isn't really a specificity to that. Many people we see with new persistent headaches since 2020 may have it as part of a long COVID syndrome (or postacute COVID syndrome), and in those cases, often it's more like “new daily persistent headache-plus.” They might have something that resembles POTS (postural orthostatic tachycardia syndrome); they might have something that resembles fibromyalgia, chronic fatigue. Often in those patients, it takes management of the whole collection of neurological syndromes to get them better, not just the headache alone. Dr Berkowitz: Well, this sounds like such a challenging condition to treat. How do you counsel patients when you've made this diagnosis - what to expect, what the goals are, what this condition is, and how you developed your certainty? It's often challenging (isn't it?) sometimes with patients with headache disorders, when we're not relying on an MRI or lab test to say, “This is the diagnosis”; telling them, it's just our opinion, based on their collection of symptoms and signs. So, how do you give the diagnosis and how do you counsel patients on what it means to them? Dr Robbins: Yeah, it's a great question because it's high stakes, because people will read online, or on social media, or on support groups that this is a dreadful condition - that no one gets better, that they're going to be afflicted with this forever, and the doctors don't know what they're doing, and, “Just don't bother seeing them.” And the truth is not that; there's so many people who can get substantially better. I tell people that it's common; in some epidemiologic studies, one in one thousand people in any given year develop new daily persistent headache, and most of those people get better (they don't seek medical care eventually, or they do, just in the beginning, and then they don't have follow-up because they got all better) - and I think that really happens. I think the people who we see in, say, a headache clinic (or even in general neurology practice) are typically the ones who are the worst of the worst. But even amongst those, we see so many stories of people who get better. So, I really try to reset expectations - like we mentioned before about assessing for treatment response and understanding that improvement will not just mean one day it switches off like it switched on (which seems unfair), but that the spikes will flatten out of pain (first), that the baseline level of intensity will then improve (second); that we turn it into a more manageable day-to-day disorder that really will have less of an impact on someone's quality of life. Sometimes people embrace that and sometimes people have a hard time. But it does require, like many conditions in neurology, incremental care to get people better. Dr Berkowitz: Fantastic. Well, Dr Robbins, thanks so much for taking the time to speak with us today. I've learned so much from your expertise in talking to you and getting to pick your brain about this and some broader concepts and challenges in headache medicine. And I encourage all our listeners to seek out your article on this condition that has even more clinical pearls on how to diagnose and treat patients with this disorder. Dr Robbins: Thanks Dr. Berkowitz - great to be with you. Dr Berkowitz: Again, for our listeners today, I've been interviewing Dr Matthew Robbins, whose article on new daily persistent headache appears in the most recent issue of Continuum, on headache. Be sure to check out other 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 practice. Right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024 or use the link in the episode notes to learn more and take advantage of this great discount. This offer ends June 30, 2024. AAN members: go to the link in the episode notes and complete the evaluation to get CME. Thank you for listening to Continuum Audio.

Posttraumatic headache is an increasingly recognized secondary headache disorder. Posttraumatic headaches begin within 7 days of the causative injury and their characteristics most commonly resemble those of migraine or tension-type headache. In this episode, Aaron Berkowitz, MD, PhD, FAAN, speaks with Todd Schwedt, MD, FAAN, author of the article “Posttraumatic Headache,” in the Continuum April 2024 Headache issue. Dr. Berkowitz is a Continuum® Audio interviewer and professor of neurology at the University of California San Francisco, Department of Neurology and a neurohospitalist, general neurologist, and a clinician educator at the San Francisco VA Medical Center and San Francisco General Hospital in San Francisco, California. Dr. Schwedt is a professor of neurology at Mayo Clinic in Phoenix, Arizona. Additional Resources Read the article: Posttraumatic Headache Subscribe to Continuum: continpub.com/Spring2024 Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Guest: @schwedtt 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, 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 can read the full article or listen to verbatim recordings of the article by visiting the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the show notes. AAN members: stay tuned after the episode to hear how you can get CME for listening.      Dr Berkowitz: This is Dr Aaron Berkowitz, and today, I'm interviewing Dr. Todd Schwedt about his article on post-traumatic headache from the April 2024 Continuum issue on headache. Dr. Schwedt is a Professor of Neurology at Mayo Clinic in Phoenix, Arizona. Welcome to the podcast today, Dr. Schwedt.    Dr Schwedt: Well, thanks so much. It's a real pleasure to be here.    Dr Berkowitz: Thanks. We're very happy to have you. So, head trauma is common, and headache following head trauma is also very common. Let's say you're seeing an otherwise healthy young patient in your clinic who had a minor car accident a few weeks ago with some head strike and whiplash, presenting now for evaluation of headache again a few weeks out from the accident. Walk us through your approach to the history and exam here when you're seeing one of these patients. Dr Schwedt: Yeah, absolutely. I'd be happy to do so. I'll start by saying, as you mentioned, this is such a common problem - patients that are coming in with post-traumatic headache). Of course, like almost everything in neurology, it's super important to get a detailed history to start with (so, doing the appropriate interview), and I usually like to start by getting some information about the injury itself - the mechanism of the injury, and the severity, and, of course, the symptoms that went along with the potential traumatic brain injury – so things we all know about. Then, of course, it's very important to understand how the patient felt prior to the injury because we know that, amongst people presenting with post-traumatic headache, oftentimes they might have had headaches even prior to their injury, and that's because having preinjury headaches is a risk factor for developing post-traumatic headache, as well as the persistence of that post-traumatic headache. If someone had headaches prior to their injury, then of course we want to know if that actually changed or not - is there a difference in the severity, or the frequency, or in the characteristics of the headaches they've been experiencing since their injury? Then, of course, you're going to ask about exactly what the symptoms are they're having now and what's concerning them the most, realizing that for a diagnosis of post-traumatic headache, it's very important to understand the timing of the onset of these headaches in relation to the injury. By definition, post-traumatic headache should have onset within seven days of the inciting traumatic brain injury - so the diagnosis of PTH, I mean, really is dependent upon that timing -  so, using ICHD (which is International Classification of Headache Disorders) criteria, it's got to start (or be reported to have started) within seven days. It's important to realize there are no specific headache characteristics that help to actually rule in or rule out post-traumatic headaches; the criteria themselves just say “any headache,” as long as it was within that seven-day period. Having said that, though, the vast majority of people who come into the clinic for evaluation - their post-traumatic headache is going to be very similar to migraine. So, like, in other words, if they didn't tell you and you didn't ask about when the headache started and you just asked about symptoms, it would seem a lot like migraines – so, very common for the headache to be moderate and severe in intensity, be associated with light sensitivity and sound sensitivity and nausea, be worse with physical and mental exertion (very much the migraine-type characteristics). As far as diagnosis, it's also, of course, important to think about other sequelae of traumatic brain injury that could be causing the headache. For example, if you're under the impression it's a mild traumatic brain injury, but in fact, there's an intracranial hemorrhage - it wouldn't necessarily be mild any longer, but of course, that could cause headaches. We should be thinking about whether there could have been injuries to the cervical spine or the musculature of the neck that could be causing more of a muscular, cervicogenic-type headache. Think about rare possibilities, like if there was a cervical artery dissection, or if there's actually a spinal fluid leak, or, again, other things that after an injury could be causing headache. Most of the time, that's not going to be the case and you would move forward with your diagnosis of post-traumatic headache.  Dr Berkowitz: Fantastic. That's very helpful to hear your approach. You just mentioned, as you said, most patients who've had minor head trauma and are presenting with headache, fortunately, have not suffered a cervical artery dissection or CSF leak or have an evolving subdural. But when you're in this early stage (just a few weeks after the initial injury) and there is headache, what features of the history or exam would clue you into thinking that this patient does need neuroimaging to look for some of these less common, but obviously very serious, sequelae of head trauma?  Dr Schwedt: So, it's things that, as neurologists, we all know about, right? But certainly, if you're concerned about a spinal fluid leak, then really someone who has a prominent orthostatic component to their headache (so, you know, much worse when they sit up or stand up, compared to lying down) could be concerning. With a cervical artery dissection, almost always you're going to have focal neurologic deficits in addition to the headaches. With intracranial hemorrhage - again, usually it's going to be fairly obvious, in that the symptoms that someone's presenting with are much more diffuse and more severe, and maybe they're actually having progression of symptoms over time rather than stability or even early improvement. Then, as we would always say, the exam is essential, right? I mean, certainly someone who's had a mild traumatic brain injury might have very subtle deficits in things like their cognition and memory of events around the injury itself - and perhaps some ocular motor deficits and some vestibular dysfunction - but they should be relatively minor compared to somebody who has one of these other etiologies for a postinjury headache. We'll point out, of course, not everyone requires imaging, again, as there's all these decision rules out there about who needs CT, for example, after an injury (and certainly not everyone does). But, you know, if people have red flags, then of course it makes sense to initially get a CT of the head, and then if symptoms persist, perhaps an MRI. Dr Berkowitz: So, once you're confident that this is a primary headache disorder - and presuming again (as in the example I gave to start us off here) that we're just a few weeks out from the initial trauma - and the patient's presenting to you for evaluation of their headache, how do you approach treatment in these patients? Dr Schwedt: Yeah, so the specificity of your question, I think, is actually quite important - so considering the timing of when you're seeing that patient really is essential. So, if we're a couple weeks out or a few weeks out and the person is still having symptoms, that tells us something to start. The majority of people who have postconcussion symptoms are going to have resolution within a few days, or a week or two, so if someone's still having symptoms at, let's say, two weeks, three weeks, four weeks, well, then that's an indicator that, unfortunately, they're likely to continue to have symptoms for some time - when we want to be a little more aggressive, if you will, with the diagnostics and management of that patient. So, like, very early on - let's say within the first few days, or even the first week or two - some patients won't require any treatment. So, if they're having mild headaches, and maybe they take something over the counter every once in a while as it gets a little more severe, that's oftentimes fine, actually. If someone's having much more severe problems with headache (even in that very acute setting), then maybe we would give them a prescription medicine just to take for their more severe headaches. But then as symptoms progress and persist, then we should of course be thinking about other ways to - in more of a preventive approach of how to - help the patient, because, unfortunately, we don't have high-quality evidence for how to treat both acute and persistent post-traumatic headaches. The recommendation for many years (and it continues to be) is that you determine the other headache type that the PTH most resembles and you treat it like that. For example, if someone has PTH and a lot of migraine symptoms, well, then you would treat it like migraine. That might mean actually giving people specific acute migraine medications. It might mean, perhaps, putting them on migraine-preventive medications. Certainly, using other forms of therapy besides medications - maybe physical therapy is needed if someone has a lot of muscular involvement of the neck. And if they're having vestibular dysfunction from the injury, maybe they need vestibular rehab. Cognitive behavioral therapies - there's some evidence, at least, to suggest that can be helpful after an injury - so, kind of the multimodal approach. We need to make sure that people are getting good sleep, or doing what we can for that to occur (we know that sleep problems, including insomnia, are quite common after a concussion, for example), and really making sure that we're treating the whole patient. The person who is still having headaches at multiple weeks after their injury - likely they're still having other symptoms, too (some of which I just named, but other symptoms as well), like symptoms of autonomic dysfunction are quite common (like orthostatic problems; autonomic type of orthostatic problems) after an injury, cognitive problems, emotional issues - people probably are anxious and not feeling well. A lot of these folks are quite healthy prior to their injury, and all of a sudden, they have, really, a significant problem, and maybe they're missing work and missing school, and so we really have to treat the patient as a whole, of course. Dr Berkowitz: Along those same lines, I was wondering - at this early stage - the patient has had still relatively recent head trauma (they are a few weeks out from this initial injury) but still having symptoms which, as you importantly highlighted, can go well beyond headache and a number of other neurologic symptoms they might have. Very common for the patient to ask, “How long is this going to last? How long am I going to feel like this?” How do you counsel patients? Obviously, the outcomes are very variable. How do you counsel patients as an expert here,  based on seeing so many of these patients a few weeks out - as you said, an otherwise healthy patient, minor head trauma, having headache, and potentially even other concussion symptoms as you mentioned - how do you counsel them on what to expect?  Dr Schwedt: I'll start by saying that this is an area of really high interest to me and my research team, as well as my clinical team - so we're not good enough yet in being able to actually predict recovery and the timing of that recovery - but this is an absolutely essential point, and for multiple reasons. The main reason is based on the question you just asked. Of course, our patients want to know, “When am I going to get better? How long is it going to take? When can I get back to my normal life (whether that be work, or playing sports, or military, or other scenarios)?” – so, that's the most important reason. And it's important as well, because from the clinician's standpoint, if you know (or if you think you know) based on prediction that someone's highly likely to continue to have symptoms – well, again, that might help you make the decision about how (you know, I'll use the word aggressive) to be with their treatment and how closely to have them follow up, and this type of thing. It's also important for research. I already mentioned that, unfortunately, there really isn't decent quality evidence (for example, for what treatments to use for post-traumatic headache), and part of that reason for that is that there have been attempts at large clinical trials, and they've failed in a sense, and I think part of the reason for that is because there is, fortunately, such a high rate of natural resolution of symptoms that if you end up enrolling those patients into these prospective clinical trials, it makes it difficult to actually study any difference you might see between a treatment and your placebo. So, if we can have and develop good, clinically useful predictive models, that would really help in each of those domains. So what do I do now? I mean, basically, it's a little bit of a cop-out answer, but what I do is, I try to look at the trajectory that the patient has had thus far (and so, you know, this is all just logical and obvious), but if a patient is already having some degree of improvement - even if they still have symptoms, but they're having some improvement over those first three weeks - well, you would more or less consider the slope of that recovery to persist more or less at the same level. On the flip side, though, if someone's there and it's been multiple weeks - and they've just had absolutely no recovery and maybe they're even feeling worse - then I'm more concerned that this might be a longer-term issue. Dr Berkowitz: That's helpful to understand both your approach and the challenges in making a firm statement on counseling our patients and using (as has been a theme in many of your helpful responses today) just, sort of, the clinical trajectory and what information that patient's giving you to try to help with the prognosis (however ambiguous it may be) and just needing time to see how the patient does. Dr Schwedt: I might just add as well, though, that there are studies that have suggested there are certain risk factors for prolonged recovery from post-traumatic headache (and there's some limitations to these studies, so, really, validation is needed), but for post-traumatic headaches specifically, I mean, probably the biggest risk factor for persistence of the post-traumatic headache is having headaches prior to the injury. So, for example, people who have migraine before TBI that then are having an exacerbation or a new headache after the injury - unfortunately, they're less likely to have resolution during the acute phase. Other factors include the severity of the injury itself - so there are certain features of the injury that if, you know, it is seemingly more severe, maybe their likelihood for resolution in the acute phase is lower. And then there are multiple other factors that have been suggested as well, including the patient's own expectations for recovery, which I find to be quite an interesting one.  Dr Berkowitz: Yeah - very important points. So, let's say that, unfortunately, the patient does continue to have headache now several months out after the trauma; how do you approach these patients with respect to treatment? Dr Schwedt: Yeah. Once someone's gotten to that point, they probably really are going to need more in the way of preventive measures (and, you know, I did mention some of these). So, if someone's having migraine-like PTH, well, then I'm probably going to end up putting them on medicines that I would use for prevention of migraine. You know, you do have to be especially careful, though, in these individuals who have had TBIs, because you want to make sure that the treatments you're starting aren't going to actually exacerbate their other symptoms, right? So, of course we know some of our migraine preventives can cause things like hypotension, or, you know, cause things like insomnia or cognitive problems, as side effects, and if people are already having those issues from their TBI, then we could actually make them overall feel worse even if we make some progress for their headaches. So, you know of course, we're always careful when thinking about side effects from these medications, but especially so, perhaps, in the patient with a concussion who's having some of these symptoms anyway. And then again - just to highlight, it's not all about medication - that's one small aspect here (one important, but perhaps small, aspect here). So, really, trying to get at lifestyle measures that can be helpful - so, again, sleep, and trying to help people to moderate their stress levels, and making sure that they have an environment that's going to facilitate the recovery (meaning, if they're having a lot of light sensitivity and sound sensitivity and these types of things, you know, doing what we can to help these individuals to be in environments that will allow them to recover). Dr Berkowitz: Yeah, all very important points - medication being just one part of treatment for these patients, as you said. But to just ask another question about medication so our listeners can learn from your expertise - I'm a general neurologist, and my experience with patients with post-traumatic headache and migraine and otherwise is that it's hard to predict who will respond to which medication (and some patients who failed many pharmaceutical medications will have an amazing response to riboflavin and vice versa) - in your experience (acknowledging that we are very limited in terms of data here), are there any migraine prophylactic agents that you feel, anecdotally, have been particularly helpful in patients with post-traumatic headaches or similar to the general migraine/tension headache population? It's very hard to predict, and it's trial and error and picking the right medication and finding the right dose (just depends on the patient). It requires the patient's patience - and our patience as well - as we sort of go through some trial and error. Dr Schwedt: Yeah, I guess. You can hardly even imagine how much I want to answer this question by saying, "Yes, with my experience, I've found that it's these two classes of medications that really work the best for folks with acute or persistent post-traumatic headache,” - but that would be disingenuous. It's so much like it is in migraine, where there is some trial and error, and, you know, again, as you say, it's so difficult to predict exactly which one is going to be the right pharmacologic agent for which patient. If access was no issue, I would go to medications that have the least side effects (which tend to be some of the newer medicines that we have for migraine), but we all know the realities of practice, and oftentimes, that's not a possibility due to access issues. Almost all of our patients that have significant postconcussion symptoms are also being managed by our neuropsychologists - and so, again, they're getting things like cognitive behavioral therapy and getting things like cognitive rehab, and they also are very helpful when it comes to workplace or school-place recommendations and accommodations. Many of our patients are being seen by our vestibular audiologists, as well, to work on their vestibular dysfunction, and vestibular rehab with physical therapy and occupational therapy. And so, you know, as you say, once you get out to multiple months, this is really a multidisciplinary, comprehensive type of treatment approach.  Dr Berkowitz: Let's say the patient has now gone one to two years out from their initial injury and you had started them on a prophylactic agent (or found the one that works for them maybe after a few trials), and they're doing great (no headaches for several months; otherwise young, healthy person), and they ask you, “Well, do you think I can just go ahead and try coming off these medications now? My injury is a long time ago. While those first few months were awful - thank you for helping me to get these headaches under control - do you think if I go off this medicine, that my headaches will come back, or am I sort of in the clear now?” How do you think about tapering patients off of preventive medications when they've had a good response at a year or so out? Dr Schwedt: That's so important, right? I mean, I think we all see patients that we inherit that end up kind of being left on medications that perhaps aren't even needed anymore, and it's certainly a mistake we wouldn't want to make. Post-traumatic headache - unlike primary headaches like migraine that tend to be present for decades - they can go away; they can resolve, and they usually do. I mean, we can't lose sight of that, right? Usually, it's going to go away on its own (as I mentioned, you know, within the first few days or weeks), and even after it's become persistent, if you can get a good treatment response, then, absolutely, after several months of that good treatment response, we should be tapering people off. Just like with any headache patient who's on a preventive, I would recommend tapering off of the effective treatment slowly, so if that's a medication, I'm usually very slowly just reducing the dose over several weeks or months (depends on how long they've been on it), usually not because I'm concerned about side effects of withdrawing the medication, but you're just testing it to make sure that the headaches aren't starting to creep back as you reduce the dose of that medication. So, it's a test, and if headaches do start to come back as you're lowering the dose, well, then, presumably you can more quickly get control of it again by elevating the dose back to where it was previously effective. For medications and treatments that don't really have dosing, the other way of doing it - so, you know, some of our medicines, of course, are given at one dose but given at intervals (like, let's say, each month or every three months) where you can't really reduce the dose - you can increase the interval between treatments. So, if you're supposed to have a treatment every month, well, if someone's doing really well, then maybe you say, “You know what? Give it an extra week.” Maybe do it in five weeks instead of four or six weeks. In that same way, you're kind of testing whether or not the medication is still really needed. Dr Berkowitz: Yeah, that makes sense as an approach here. In addition to your clinical expertise, Dr Schwedt, you're also a researcher in this area. Tell us, what's on the horizon for the future of diagnosis and treatment of patients with post-traumatic headache?  Dr Schwedt: There's a lot of exciting things on the horizon. It's really encouraging that despite, for example, the lack of evidence currently that we have for treatment, and perhaps not as much preclinical and clinical research into post-traumatic headache as we need, the exciting part is that there's a lot going on. Fortunately, the funding environment for such research has been decent over the past so many years, and so, again, there's almost certainly going to be meaningful breakthroughs here in the near future. Some of our own work - for example, we do a lot of neuroimaging research of post-traumatic headache. One of the main areas of controversy in the headache field is whether or not post-traumatic headache and migraine are really the same thing or are they truly distinct headache disorders? And so, like, a lot of our work has gone towards addressing that - both through neuroimaging, as well as just examining outcomes and symptoms and whatnot - to see where there are similarities and differences. And I'm absolutely biased when it comes to addressing this, but I feel strongly that they really are distinct headache disorders. And that's important, because that means that we need to continue to study them as distinct disorders and we can't just fall back to the idea of saying, “Well, PTH of a migraine phenotype is migraine, and we already have migraine therapy, so let's just use those,” because I think all of us that see patients with PTH in clinical practice realize that our migraine treatments don't work as well for PTH as they do for migraine. So, we really need to continue down the path of understanding the mechanisms underlying PTH, the mechanisms of what makes PTH persist (you know, why it persists in some people and not others), and then what we can do to intervene. I think a major topic, I believe, in determining best treatment approaches is also kind of related to the way you were asking me these questions - it's related to the timing of the intervention. Much of what's been done in studying treatment of PTH is done after it's already persistent, and so in some of these studies, including ours (I mean, it's not a criticism; including ours) - sometimes, these people have had post-traumatic headache for five years or ten years at the time that you enroll them into a study. And, you know, at that point, that's probably a very different population as far as mechanisms and who might respond to which treatments (compared to if you were studying those folks, let's say, in the first few weeks or in the first couple months). There's preclinical evidence (from rodent models of mild traumatic brain injury and post-traumatic headache) that the earlier you intervene, the more effective that intervention is going to be in treating that headache and preventing its persistence, and I would think we could logically presume that's probably the case in people as well. But, of course, we don't want to expose everybody early on to treatments if they don't need it (I mean, if they're going to have natural resolution, then that would actually be inappropriate [to expose them to treatments]). And that's where the prediction comes in. If we had good predictive models of - oh, you know, even though they're only a week into their headache, based on their pre-TBI factors and other characteristics, that they're very likely to have persistence - well, maybe that's the patient where they should have an earlier intervention, and, you know, in another patient, maybe not.  Dr Berkowitz: It's great to hear about your work and the work of others to help us understand this very, very common condition (and that's been a theme in many of our questions), one in which we do our best, but are often limited by, our scientific understanding and the data on how to best manage these patients' headaches. I've learned a lot from our discussion - both clinically, and I'm excited to have learned more about your work and what's on the horizon to help us take care of these patients. Thank you very much, Dr Schwedt, for joining me on Continuum Audio today. Again, for our listeners, I've been interviewing Dr Todd Schwedt, whose article on posttraumatic headache appears in the most recent issue of Continuum on headache. Be sure to check out other Continuum Audio podcasts from this and other issues. Thank you so much 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 practice. And right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024, or use the link in the episode notes, to learn more and take advantage of this great discount. This offer ends June 30, 2024. AAN members: go to the link in the episode notes and complete the evaluation to get CME. Thank you for listening to Continuum Audio.    

Episode 331: Neurology VMR – Headaches and loss of sensation in the left leg We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Hans presents a case of headaches and loss of sensation in the left leg to Andrew and Maria. Neurology DDx Schema  Hans Kaus  Hans Kaus received his… Read More »Episode 331: Neurology VMR – Headaches and loss of sensation in the left leg

  Episode title: Episode 323: Neurology VMR – Visual hallucinations Episode description: We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Valeria presents a case of visual hallucinations to Greg and Umbish. Neurology DDx Schema   Valeria Roldan @valeroldan23   Valeria Roldan was born and raised in Lima, Peru. She… Read More »Episode 323: Neurology VMR – Visual Hallucinations

Traumatic spinal cord injury is a potentially devastating disorder. Best practices in clinical care for these patients has evolved, with implications for long term outcomes. In this episode, Aaron Berkowitz, MD, PhD, FAAN, speaks with Saef Izzy, MD, author of the article “Traumatic Spinal Cord Injury,” in the Continuum February 2024 Spinal Cord Disorders issue. Dr. Berkowitz is a Continuum® Audio interviewer and professor of neurology at the University of California San Francisco, Department of Neurology, a neurohospitalist, general neurologist, and clinician educator at the San Francisco VA Medical Center and San Francisco General Hospital in San Francisco, California. Dr. Izzy is an assistant professor of neurology at Harvard Medical School and an associate neurologist in the Department of Neurology, Divisions of Neurocritical Care and Cerebrovascular Diseases at Brigham and Women's Hospital in Boston, Massachusetts. Additional Resources Read the article: Traumatic Spinal Cord Injury Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud American Academy of Neurology website: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Guest: @SaefIzzy Full 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, a companion podcast of 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 can read the full article or listen to verbatim recordings of the article by clicking on the link in the show notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the episode notes. AAN members, stay tuned after the episode to hear how you can get CME for listening. Dr Berkowitz: This is Dr. Aaron Berkowitz. Today, I'm interviewing Dr. Saef Izzy about his article on traumatic spinal cord disorders from the February 2024 Continuum issue on spinal cord disorders. Dr. Izzy is an Assistant Professor of Neurology at Harvard Medical School and an associate neurologist at Brigham and Women's Hospital in Boston, Massachusetts. Welcome to the podcast, Dr. Izzy. So, let's say a patient comes to the emergency room with an acute spinal cord injury due to a car accident. Walk us through your approach. What's going through your mind when you hear this pager go off and you're walking down to the emergency room; what are you thinking? Dr Izzy: Yeah, great question. So, one of the first question is, what's the medical status of the patient? And, starting from, “How sick is the patient? (looking at the ABCD - basically, airway, breathing, circulation), make sure the patient is stable from that perspective, with the specific focus then going to be the injury level and the injury severity. And with that, once the patient is clinically stable, we try to pay very close attention to that aspect, especially since we know the patient is coming with a spinal cord injury from the prefield assessment. So, having a very close assessment to the spinal cord using a standardized tool (such as the ASIA, which is the American Spinal Injury Association Impairment Scale) will be very helpful to communicate the level of injury to the rest of the team, which usually is going to be a multidisciplinary team approach from the emergency room into neurosurgery, neurology and other disciplines where we'll be involved. So, having a standardized tool will be a key. ASIA, as a scale - it starts with a letter “A” - and to be A when there is a complete injury, with loss of motor and sensory, and E is basically normal exam (a neuro exam with normal motor and sensory examination). And between B to D, they have some preserved voluntary anal contraction and some of the reflexes, such as the bulbocavernosus reflexes, with a various degree of motor and sensory. Having an early introduction into this scale will be super helpful to communicate with other services. Then will be the decision about who I should image, and also, whether I should clear the C-collar or not. And this is also another sort of decision making, comes into the patient mental status, the injury severity, the level of injury, as well as ability to perform a reliable neurological examination - all plays a role into this decision. In this article, we have elaborated on the clinical decision making - an approach in the acute setting - and we provided, in Figure 1, a comprehensive approach about patient we should think about imaging and what modality of imaging, as well. Dr Berkowitz: Perfect, that's so helpful. So, you're thinking through the ABCDs, as you mentioned. And then a detailed neurologic exam to get a sense of the degree of injury. And then you mentioned the decisions about imaging. Tell us a little bit about how you think about who to image, what to image, how to image, after you've done your neurologic exam. Dr Izzy: So, the imaging in general, as we know, that previously used to be an x-ray. But the recent literature really focus on utilizing the utility of high-quality CAT scans as it's provide more comprehensive characterization of vertebral fractures. And that will be very helpful to identify the level and severity of radiographic injury. However, MRI will always be superior, as it also provides the extent of the cord compression, signs of cord injury, as well as could help us rule out ligamentous injury within, especially, the first 48 hours post the event. In addition to that, we have to pay attention to a patient at risk of having vascular injuries, as many spinal cord, especially the cervical and skull-based injuries, can associate with blunt cerebrovascular injuries, which often missed in the emergency room, and even in the acute stay, as no one would have thought about that aspect. That's why, in this article, we have highlighted the role of Memphis criteria, which is a very valuable tool to identify patients at risk to be scanned. And also the Biffl Scale, which used to be known at the Denver, and modified Denver Scale, to assist classifying the level of vascular injury. Dr Berkowitz: Great. So, I want to pick up on a number of the things you mentioned there. So, let's talk about injury to the bony structures that could result in impingement on neurologic structures, such as the nerve roots or cord or cauda equina. So, Often, neurology and neurosurgery are consulted together in these patients, right? And both arrive at the bedside in the emergency room. Tell us a little bit about working with our neurosurgical colleagues to figure out who should go for surgery, what type of surgery they should go for, and the neurologist's role in helping in that decision making. Dr Izzy: I believe the neurologists have a significant role in the acute setting, especially with performing a very thorough, refined neurological examination when it comes into assessing the cranial nerve, because often traumatic spinal cord injury could associate with traumatic head injury. In addition to that, perform a very thorough motor and sensory exam, with a specific look into reflexes, as well as anal reflexes. And documenting that, in conjuncture with the neurosurgery colleague, will be super helpful. We have to know that doing neurological assessment, or also relying on them, the ASIA scale is a key, but also could be confounded in the acute setting with other multisystemic events, including respiratory failure, using some pain medication, traumatic brain injury, hypotension, which all could confound the initial exam. That's why having a repeated exam for this patient throughout the hospital stay will be a key, especially when we are using some of these examination in the acute setting to guide our prognostication. Also, when it comes into the neurological assessment, looking into, not only the level of injury, but paying attention into the levels below. And documenting this exam is also a very critical aspect of assessment. One of the early decisions we share - many times when we, as neurologists, get consulted on these patients who should go to surgery, and that's a whole topic by itself discussed thoroughly in this article about the literature on a patient who should basically pursue surgery. And, one of the main highlight of the literature that, pursuing surgery in less than 24 hours has been associated with improved outcomes. Yet the literature on that still need further evaluation, especially now the most common practice that patients with worsening exam, mass effect, and epidural mass takes priority. But further studies on this area definitely require further exploration. Dr Berkowitz: Another aspect you mentioned is blunt cerebrovascular injury - so, injury to the carotid or vertebral arteries in the neck or in the skull base. So, are CT angiograms part of the standard neuroimaging now for patients with spine injury, or on a case-by-case basis, or perhaps should they be? Dr Izzy: Great question. It's not. That's why paying specific attention for a patient at risk, and that's where the Memphis screening protocol takes place. And we encourage our colleagues from neurology and neurosurgery, as well as emergency department, to try to keep this sort of screening, helpful protocol handy when approach traumatic spinal cord injury. More specifically patients, who have basilar skull fracture with involvement of the carotid canal; the one with a basilar fracture with involvement of the petrous bone; the cervical spine fracture with neurological exam that doesn't necessarily explained by imaging; having a Horner syndrome on neurological exam; fractures pattern involve LeFort II or III fractures; as well as neck soft injury; the seatbelt sign - these are all signs that could really raise the red flag that there is a possible underlying vascular injury that require evaluation by CT angiogram in the emergency room to further identify. Once we identify the vascular injury, there is another helpful and valuable score, which is the Biffl Scale, or the - what also well known to be Denver or the modified Denver. And that one will further characterize the injury from level 1 to 5, 1 involving the luminal irregularity and dissection with less than 25% luminal narrowing - that's the 1. And 2, more than 25% narrowing. The 1 and 2 carries different prognostication and management, because these two we can always think about starting antiplatelet or anticoagulation on the first two, while 3 is aneurysm or pseudoaneurysm in the artery, while 4 is occlusion or thrombosis, and 5, usually transection of the vessel, the free extravasation. Grade 3 and above, usually, medical treatment has not much of a big role and discussion with the vascular neurosurgery or neuroendovascular colleague will be super helpful. Dr Berkowitz: You started alluding to the next question I was going to ask you related to these. As neurologists are often consulted when there's vascular injury, traumatic vascular injury, about the questions of the risks and benefits of starting antiplatelets or anticoagulation. You mentioned that, in extreme cases - obviously if the vessel is transected or there's extravasation - there'll probably be great danger in starting those types of agents. But often we're consulted for the lower grades, such as a dissection or a luminal irregularity. And the question comes up, what is the extent of the benefit of antiplatelet and anticoagulation when balanced with the risk? – that these are often patients with polytrauma, not just affecting the nervous system, but often systemic organs as well. How do you balance the risk and benefit of treating these traumatic vascular injuries with antiplatelets or anticoagulation, to wanting to reduce the stroke risk related to these, on the one hand, and taking into account the extensive injuries that often accompany these? Dr Izzy: Yeah, absolutely. Very clinical relevant question. The short answer: there is no randomized clinical trials that compared antiplatelet therapy with anticoagulation, whether it's unfractionated or low-molecular-weight heparin, for the treatment of blunt cerebrovascular injury- not even compare the timing to start. That's why it comes into the clinical judgment when it comes to answer this question. As far as level of injury defined by Biffl Scale, Grade 1 and 2, when there is a dissection less than or more than 25%, it's reasonable to start either or. And that comes into the context of the patient. In general, most of these patient comes with other multisystemic event. Could be having a traumatic brain injury with contusion, and the size of the contusion maybe also play a role in this decision where there is risk of contusion expansion or bleeding in other parts of the body, which makes anticoagulation very critical and dangerous with these patients. Maybe starting aspirin could be reasonable and safe, as that comes into a multidisciplinary discussion with our colleague from neurosurgery, ortho (if they are involved), as well as the primary ICU team. Having a thorough discussion about the pros and cons of this decision is a key. Most specifically, it's about balancing the risks and benefits in management. When it comes into high grade (3 and above) involving pseudoaneurysm, we know that antiplatelet or anticoagulation might play a lesser role; might be beneficial to some extent (not very well studied in this cohort of patients). But having a discussion when it comes into vascular malformation involving arteriovenous fistula or near occlusion of a vessel with our neuroendovascular colleague and vascular neurosurgeon will be always a key. Just one more point to make - that if it's too risky to start in the acute setting because of other multisystemic involvement, having a repeat imaging in a few days might be also helpful in assessing the progression of the vascular injury - could also be helpful from that setting. If the patient start developing new neurological symptoms, rather than just blaming it on the cervical or thoracic spine, thinking about new-onset strokes that happen would be a key to elaborate there, as we know the duration - for how long. If we end up starting patients on anticoagulation, or antiplatelets such as aspirin, for how long we should keep it for? It's still controversial, but the common approach is to start when it's safe from clinical standpoint and consider keeping it for three to six months. And repeat follow up imaging in the outpatient setting to assess that vascular injury and determine the duration of treatment will also be a key. Dr Berkowitz: Shifting gears again here - you're involved in the acute setting here, diagnosing and managing these patients, often otherwise healthy patients who've suffered a devastating accident. How do you begin the conversation about communicating the prognosis, often probably the first question from the patient's family, “Are they going to walk again?” Obviously, a lot of factors go into this and it can be hard to prognosticate from the first moments of injury. But how do you begin to have that conversation when that question is asked for the first time, often in the emergency room? Dr Izzy: As a neural intensivist, commonly involved in the acute management of traumatic spinal cord injury patients, we try to focus on the acute management of patient, try to inform families that it's too early to provide an accurate prognostication of the long-term outcome. Especially, that the acute course of the disease could associate with so many other clinically relevant variables that could have an impact on the long-term outcome, such as respiratory failure, hypotension, in terms of neurogenic or spinal shock, in addition to rate of infections. In such acute, early, or superacute stage of the disease, there's still not much known about the correlation with the very-long-term outcomes. As I mentioned earlier, even the very first ASIA scale, the first neurological assessment could be easily confounded by many of these factors. Once we address the hypotension, treat the infection, or even try to control the respiratory failure, we have seen that might improve the neurological assessment - could be in the acute setting. That's why we try to provide the families with the clinical status of the patient and postpone any discussion on neuroprognostication until the patient in a stable clinical state and when we have a better assessment of the neurological and hemodynamic state. Dr Berkowitz: Tell us now, in closing, what does the future hold for the treatment of these patients with acute spinal cord injury? Dr Izzy: Despite all the unknowns about the course of the disease, when it comes into the long-term outcomes and the increasing rate of early and delayed mortality in this disease and poor outcome, there are many ongoing attempts to test various pharmacological and nonpharmacological interventions to achieve neuroprotection and enhanced functional outcome after traumatic spinal cord injury. There are many promising attempts for transplantation of neuronal embryonic mesenteric stem cells, as well as oligodendrocyte precursor cells. Two or three clinical trials now ongoing, trying to assess the benefit for long-term outcome. The future is still optimistic that some of these initiatives might eventually transition to the bedside application and potentially leading to significant improvement in the long-term outcomes of our patient. However, many of these initiatives are still investigational but carries the hope. Our role as a clinical team - always satisfying taking care of traumatic spinal cord injury patients and their family and guide them through the journey to recovery. Dr Berkowitz: Dr. Izzy, thanks so much for taking the time to speak with us today. I encourage all of our listeners to read your phenomenal article. We could only scratch the surface today in our discussion on this very complicated, challenging area of neurologic practice, but your article lays out a lot of very helpful, practical clinical elements in the diagnosis, treatment, and prognostication in patients with spinal cord injury. Dr Izzy: Absolutely. My pleasure. Dr Berkowitz:  Again, for our listeners, I've been interviewing Dr. Saef Izzy, whose article on traumatic spinal cord disorders appears in the most recent issue of Continuum on spinal cord disorders. Be sure to check out other 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, please consider subscribing to the journal. There's a link in the episode notes. We'd also appreciate you following the podcast and rating or reviewing it. AAN members, go to the link in the episode notes and  complete the evaluation to get CME for this article. Thank you for listening to Continuum Audio.

Happy New Year, Neurophiliacs! We are thrilled to start 2024 interviewing the one and only, Dr. Aaron Berkowitz. Throughout the hour we covered Aaron's incredible journey into neurology, his work abroad and the process behind creating "One By One By One: Making A Small Difference Amid A Billion Problems," and the supply-demand mismatch of global neurology in developing countries. Dr. Aaron Berkowitz is a professor of clinical neurology at UCSF where he serves as a neurohospitalist, general neurologist, and clinician-educator at the San Francisco VA and San Francisco General Hospital.  He previously served as director of global neurology at Brigham and Women's Hospital and associate professor of neurology at Harvard Medical School. As Health and Policy Advisor to Partners In Health, Senior Specialist Consultant to Doctors Without Borders,  prior Chair of the AAN Global Health Section, and prior Co-Chair of the ANA Global Health Section, he has worked tirelessly to improve access to neurologic care and education worldwide. This work has been recognized by the Mridha Humanitarian Award from the American Brain Foundation in 2018 and the Viste Patient Advocate of the Year Award from the AAN in 2019. His work as a neurology educator has been recognized by the Residency Teacher of the Year Award from the MGH/Brigham Neurology Residency program in both 2018 and 2020, the O'Hara Excellence in Preclinical Teaching award from Harvard Medical School in 2016, appointment to the editorial board of Continuum, and frequent invitations to discuss neurology topics on the popular Clinical Problem Solvers podcast. He has published over 80 peer-reviewed articles, several book chapters including the neurology chapter for the Oxford Manual of Humanitarian Medicine, and four books including the neurology textbook Clinical Neurology and Neuroanatomy: A Localization-Based Approach and One by One by One: Making a Small Difference Amid a Billion Problems about his work caring for patients with brain tumors in rural Haiti.Follow Dr. Aaron Berkowitz on Twitter @aaronlberkowitz Follow the Neurophilia Podcast on Twitter and Instagram @NeurophiliaPodFollow Dr. Nupur Goel on Twitter @mdgoelsFollow Dr. Blake Buletko on Twitter @blakebuletkoSupport the show

Episode title: Episode 317: Neurology VMR – Generalized weakness Episode description: We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Kirtan presents a case of generalized weakness to Vivek and Hannah. Neurology DDx Schema   Kirtan Patolia @KirtanPatolia   Kirtan Patolia is a second-year Internal Medicine resident from John H.… Read More »Episode 317: Neurology VMR – Generalized Weakness

Episode title: Episode 312: Neurology VMR – Frequent stumbling Episode description: We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Valeria presents a case of frequent stumbling to Nilayan and Subhangi. Neurology DDx Schema Valeria Roldan Valeria is a medical student at Universidad Peruana Cayetano Heredia. She was born and… Read More »Episode 312: Neurology VMR – Frequent Stumbling

Episode 305: Neurology VMR – Shallow breathing Episode description: We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Vaness presents a case of shallow breathing to Maria and Sridhara. Neurology DDx Schema   Vanessa Roque   Vanessa, a proud Filipino through and through, has dedicated herself to medicine. She has… Read More »Episode 305: Neurology VMR – Shallow Breathing

Episode 299: Neurology VMR – Clumsiness Episode description: We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, María presents a case of clumsiness to Andrea and Sridhara. Neurology DDx Schema   Andrea Mendez Colmenares @andreamendez92 Andrea is a Venezuelan medical doctor and cognitive neuroscientist specializing in advanced white matter imaging.… Read More »Episode 299 – Neurology VMR – Clumsiness

We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Dr. Gabriela Pucci presents a case of right arm weakness to Promise and Ravi.  Promise Lee @promiseflee Promise Lee is currently a 3rd year medical student at Loyola University Chicago Stritch School of Medicine. She is an aspiring internal medicine… Read More »Episode 290 – Neurology VMR – Vertigo

A conversation between ⁠⁠JLJ⁠⁠ EiC, Aaron Berkowitz, and author, Jill Santopolo⁠, on her newest book, "Stars in an Italian Sky." ⁠⁠Youtube⁠⁠ ⁠⁠Patreon⁠⁠ ⁠⁠Paypal Donations

A conversation between ⁠⁠JLJ⁠⁠ EiC, Aaron Berkowitz, and author, Elinor Lipman, on her newest book, "Ms. Demeanor." Youtube ⁠⁠Patreon⁠⁠ ⁠⁠Paypal Donations

A conversation between ⁠JLJ⁠ EiC, Aaron Berkowitz, and author, ⁠Josh Weiss, on his newest book, "⁠Sunset Empire⁠." ⁠Youtube⁠ ⁠Patreon⁠ ⁠Paypal Donations

We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Dr. Ravi Singh presents a case of right arm weakness to Yazmin and Sridhara. Neurology DDx Schema Yazmin Heredia @minheredia Yazmin is a Mexican Graduate from the Universidad Autonoma de Yucatan. During her medical training, she developed a strong interest… Read More »Episode 283 – Neurology VMR – Right arm weakness

A conversation between JLJ EiC, Aaron Berkowitz, and author, Jennifer Steil, on her newest book, "Exile Music." Youtube Patreon Paypal Donations --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app

We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Yazmin presents a case of lethargy and myoclonus to Kiara and Maria. Neurology DDx Schema Maria Jimena Aleman @MariaMjaleman María Jimena Alemán was born and raised in Guatemala where she currently works in community and rural health care. After suffering from… Read More »Episode 276: Neurology VMR – Lethargy and Myoclonus

A conversation between JLJ EiC, Aaron Berkowitz, and author, Peter Orner, on his newest book, "Still No Word From You; Notes in the Margin." Youtube Patreon Paypal Donations --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app

We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time,Valeria presents a case of headache and altered mental status to Joy and Mattia. Neurology DDx Schema Valeria Roldán @valeroldan23 Valeria is a medical student at Universidad Peruana Cayetano Heredia. She was born and lives in Lima, Perú. She hopes to… Read More »Episode 269: Neurology VMR – Headache and altered mental status

We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, John presents a case of diplopia to Valeria and Madellena. Neurology DDx Schema   John Acquaviva @DrJAStrange John Acquaviva is a fourth-year medical student attending Lake Erie College of Osteopathic Medicine in Erie, Pennsylvania. He has a passion for both clinical… Read More »Episode 263: Neurology VMR – Diplopia

We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, CPSolvers team member Rafael Medina presents a case of frequent falls for CPSolvers team member Yazmin and Alice. Neurology DDx Schema Rafael Medina dos Santos @Rafameed Rafael Medina dos Santos is a Brazilian medical graduate. Before medicine, Rafael wanted to be… Read More »Episode 255: Neurology VMR – Frequent Falls

We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Valeria Roldan presents a case of tremors and myoclonus to Dr. Aaron Berkowitz. Neurology DDx Schema   Valeria Roldán @valeroldan23 Valeria is a medical student at Universidad Peruana Cayetano Heredia. She was born and lives in Lima, Perú. She hopes to pursue… Read More »Episode 247: Neurology VMR – Tremors & Myoclonus

Sara Schaefer interviews author neurologists Elie Sternberg, author of NeuroLogic and other books, and Aaron Berkowitz, author of One by One by One, about how they got started with writing, their writing and publication process, what they find fulfilling, and how it influences their neurology practices.

 We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time Dr. Doug Pet presents a case of slurred speech to Angelita and Diane.  Neurology DDx Schema Doug Pet @doug_pet Doug is a resident in neurology at UCSF. He grew up surrounded by cow farms and crab-apple trees in New Milford,… Read More »Episode 237: Neurology VMR – Slurred Speech

We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Vijay presents a case of left upper extremity weakness to Vale and John.   Neurology DDx Schema   Download CPSolvers App here Patreon website  

JLJ Editor-in-Chief, Aaron Berkowitz continues to explain what the JLJ is looking for in submissions. https://www.youtube.com/channel/UCHOXkjLpr6SKsYHwZYMTGMg https://www.patreon.com/thejlj Paypal Donations

We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Maria presents a case of increased drowsiness to Dr. Mathieu Brunet and Dr. Mattia Rosso. Neurology DDx Schema Maria Jimena Aleman Maria Jimena Aleman María Jimena Alemán was born and raised in Guatemala where she currently works in community and rural health care.… Read More »Episode 220: Neurology VMR – Drowsiness

JLJ Editor-in-Chief, Aaron Berkowitz explains what how the JLJ thinks about genre. https://www.youtube.com/channel/UCHOXkjLpr6SKsYHwZYMTGMg https://www.patreon.com/thejlj Paypal Donations

JLJ Editor-in-Chief, Aaron Berkowitz explains what the JLJ is looking for in submissions. https://www.youtube.com/channel/UCHOXkjLpr6SKsYHwZYMTGMg https://www.patreon.com/thejlj Paypal Donations

We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Maria presents a case of episodic transient loss of consciousness to Gabriel and Ravi. Schema 1 Schema 2 Neurology DDx Schema Maria Jimena Aleman Maria Jimena Aleman was born and raised in Guatemala where she currently is a medical student in Universidad Francisco… Read More »Episode 211: Neuro VMR – Episodic transient loss of consciousness

We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Gabriela presents a case of impairment of speech to Gabriel and Valeria. Neurology DDx Schema Want to test your learning? Take our Episode Quiz Gabriela Pucci Gabriela has graduated from Medical School at Unicamp and recently finished her neurology residency at Unesp, both… Read More »Episode 199: Neurology VMR – Diplopia

We continue our campaign to #EndNeurophobia, with the help of Dr. Aaron Berkowitz. This time, Gabriela presents a case of impairment of speech to Maria and Kirtan. Neurology DDx Schema Want to test your learning? Take our Episode Quiz Gabriela Pucci Gabriela has graduated from Medical School at Unicamp and recently finished her neurology residency at Unesp,… Read More »Episode 193: Neurology VMR – Impairment of Speech

Dr. Aaron Berkowitz is a leading voice in neurology, global health and medical education. He's also concerned and involved with issues of social justice. Aaron has written a book called One by One by One: Making a Small Difference Amid a Billion Problems, to inspire others to see the world differently and get involved in … Continue reading "152. Aaron Berkowitz – One by One by One: Making A Small Difference Amid a Billion Problems" The post 152. Aaron Berkowitz – One by One by One: Making A Small Difference Amid a Billion Problems first appeared on School for Good Living Podcasts.

SUMMARY In his memoir ONE BY ONE BY ONE, Dr. Aaron Berkowitz traces his journey as a young doctor grappling to bridge the gap between one of the world's richest countries and one of the world's poorest. On assignment in Haiti with Partners in Health, he meets Janel, a 23-year-old man with the largest brain tumor he or any of his colleagues at Harvard Medical School have ever seen. Trying to make the first big save of his medical career as a neurosurgeon, and determined to “to bring the benefits of modern medical science to those most in need” and work toward “solidarity rather than charity alone,” Dr. Berkowitz aims to save Janel's life by bringing him back to Boston for a 12-hour brain surgery.  With heart-wrenching twists and turns, the story of Janel's uncertain medical future parallels Dr. Berkowitz's own uncertainties as a doctor. Berkowitz brings the reader to the front lines of global humanitarian work as he struggles to overcome the challenges that arise when well-meaning intentions give rise to unintended consequences, when cultures and belief systems clash, and when it's not clear what the right thing to do is, let alone the right way to do it. KEY FACTS About 4 billion people lack access to basic healthcare. Haiti is the poorest country in the Western Hemisphere. More than 10,000 non-governmental organizations (NGOs) work in Haiti (one for every 1,000 people), yet Haiti remains one of the poorest countries, with some of the worst health, education, and sanitation statistics in the world. QUOTES FROM BERKOWITZ "I learned how a few individuals working together might just be able to make a small difference in those big billions, one by one by one.” “From illiteracy to entitlement and corruption, from going to the bathroom with the door open to refusing to sit near the bathroom, Haiti's inequities and their juxtaposition are in plain view before even arriving there.” “PIH [Partners in Health] describes its work as being based on solidarity rather than charity alone. Charity is necessary, of course: those who have more should help those who have less. But charity means us giving to them, to some abstract all. Solidarity redefines this relationship. It invites all of us to share with each other because we are each part of the same all.” “PIH recognized early on that health is not only about medicine but also about combating poverty.” “If we frame problems in terms of their constraints rather than their possibilities, prioritizing risk avoidance above all else, we are less motivated to find solutions.” BUY One by One by One: Making a Small Difference Amid a Billion Problems RECOMMENDATION Learn more about Partners in Health and their mission by visiting their website. Connect with us! Facebook Instagram Twitter YouTube  Website Special thanks… Music Credit Sound Editing Credit

Description: We continue our campaign to #EndNeurophobia led by Aaron Berkowitz! This time, Doug presents a case of headache and blurry vision to Hannah and Dhruv. Neurology DDx Schema Dhruv Srinivasachar Dhruv Srinivasachar is a soon-to-be 1st year Medicine-Pediatrics resident at Western Michigan University and a graduate of Virginia Commonwealth University School of Medicine (the Medical College of Virginia for all… Read More »Episode 179: Neurology VMR – Headache and blurry vision

Thank you for your continued support and please give us feedback here! Dan, Doug, and Lindsey are joined by expert neurologist Dr. Aaron Berkowitz to help break down a consult question about back pain and double vision Schema Download CPSolvers App here Patreon website

We continue our campaign to #EndNeurophobia by tackling this neurology clinical unknown, with the guidance of Aaron Berkowitz. Episode Quiz Download CPSolvers App here Patreon website Maria Jimena Aleman Maria Jimena Aleman was born and raised in Guatemala where she currently is a medical student in Universidad Francisco Marroquin. After suffering from long standing neurophobia,… Read More »Episode 167: Unilateral sensory changes

We continue our mission to #EndNeurophobia with an episode of Neurology VMR with Dr. Aaron Berkowitz  Download CPSolvers App here Patreon website Episode Quiz Dhruv Srinivasachar Dhruv Srinivasachar is a 4th year medical student at Virginia Commonwealth University School of Medicine (the Medical College of Virginia for all the veteran attendings out there). Introduced to… Read More »Episode 160: Neurology VMR: Hiccups + vertigo

Aaron Berkowitz, MD PhD, is the founding Director of Global Health at Kaiser Permanente Medical School and was the founding Director of the Global Neurology Program at Brigham and Women's Hospital in Boston and directed the first-year Mind-Brain-Behavior course at Harvard Medical School. As a consultant for Partners In Health and advisor to Doctors Without Borders, Dr. Berkowitz has worked in Haiti, Malawi, Vietnam, and on the Navajo reservation in New Mexico. Dr. Aaron Berkowitz will discuss his new book, One by One by One which offers invaluable and inspiring lessons for anyone who hopes to make a small difference in the world's billions of problems, one step at a time.

Aaron Berkowitz, MD PhD, is the founding Director of Global Health at Kaiser Permanente Medical School and was the founding Director of the Global Neurology Program at Brigham and Women's Hospital in Boston and directed the first-year Mind-Brain-Behavior course at Harvard Medical School. As a consultant for Partners In Health and advisor to Doctors Without Borders, Dr. Berkowitz has worked in Haiti, Malawi, Vietnam, and on the Navajo reservation in New Mexico. Dr. Aaron Berkowitz will discuss his new book, One by One by One which offers invaluable and inspiring lessons for anyone who hopes to make a small difference in the world's billions of problems, one step at a time.

Originally aired on WYTX-FM 6/13/20. Guests: Harvard Neurosurgeon Dr. Aaron Berkowitz, "One by One by One"; Child psychologist Dr. Abigail Gewertz on how to talk to your kids about scary times; Author Stephen Haff, "Kid Quixotes"; Author Katherine Snow Smith "Rules of the Southern Rulebreaker"; Going to the doctor during the pandemic.

Originally aired on WYTX-FM 6/13/20. Guests: Harvard Neurosurgeon Dr. Aaron Berkowitz, "One by One by One"; Child psychologist Dr. Abigail Gewertz on how to talk to your kids about scary times; Author Stephen Haff, "Kid Quixotes"; Author Katherine Snow Smith "Rules of the Southern Rulebreaker"; Going to the doctor during the pandemic.

Originally aired on WYTX-FM 6/13/20. Guests: Harvard Neurosurgeon Dr. Aaron Berkowitz, "One by One by One"; Child psychologist Dr. Abigail Gewertz on how to talk to your kids about scary times; Author Stephen Haff, "Kid Quixotes"; Author Katherine Snow Smith "Rules of the Southern Rulebreaker"; Going to the doctor during the pandemic.

In One by One by One, Berkowitz traces what he learns and grapples with as a young doctor trying to bridge the gap between one of the world's richest countries and one of the world's poorest to make the first big save of his medical career.

In One by One by One, Berkowitz traces what he learns and grapples with as a young doctor trying to bridge the gap between one of the world's richest countries and one of the world's poorest to make the first big save of his medical career.

In One by One by One, Berkowitz traces what he learns and grapples with as a young doctor trying to bridge the gap between one of the world’s richest countries and one of the world’s poorest to make the first big save of his medical career.

With Covid-19 surging in so many states and a president who tells us the lethal virus is “fading away,” and Trump's former National Security Advisor confirming what we already know, that the POTUS is not “fit for the job,” things are looking pretty bleak in the U.S.. But don't despair. Just when you need it, The Halli Casser-Jayne Show brings you an inspiring story, the tale of a true American hero, Dr. Aaron Berkowitz, his story told in his new book ONE BY ONE BY ONE, MAKING A SMALL DIFFERENCE AMID A BILLION PROBLEMS. Welcome to The Halli Casser-Jayne Show always available at Halli Casser-Jayne dot com, on whichever is your favorite app, and on your Alexa device too.Up first, Halli and her partner in politics, former White House correspondent and Newsweek and Time veteran Matthew Cooper slice and dice all things politics. This week we talk Bat Fever (aka Covid-19), Blabbermouth John Bolton, Election2020, police reform, and the passing of an American icon, the end of an era, Jean Kennedy Smith, the last surviving sibling of President John F. Kennedy, and so much more. Then in our second half-hour: The name Dr. Aaron Berkowitz may not be familiar to you, but he's someone you want to meet. His story is powerful, and in these wretched times, it's an inspiring story. It begins here: Dr. Aaron Berkowitz has just finished his medical training when he was sent to Haiti on his first assignment with Partners In Health, a global health organization that brings health care to the most vulnerable around the world. There, he meets Janel, a 23-year-old man with the largest brain tumor Berkowitz or any of his neurosurgeon colleagues at Harvard Medical School have ever seen. Determined to live up to PIH's mission statement, Berkowitz tries to save Janel's life. And that's just the beginning, the whole story told by Dr. Berkowitz in his inspiring new book ONE BY ONE BY ONE: MAKING A SMALL DIFFERENCE AMID A BILLION PROBLEMS.It's a jam-packed hour. Covid-19, John Bolton, Election2020, the Montana Senate race, John F. Kennedy, Black Lives Matter, Election 2020, Haiti, an inspirational story, Jean Kennedy Smith -- all this week on The Halli Casser-Jayne Show Podcast, always available at Halli Casser-Jayne dot com and on whichever is your favorite app and on your Alexa device too.

#therichsolution #onebyonebyone #globalhealthJoin me with my guest Aaron Berkowitz, MD author of "#One By One By One". Dr. Berkowitz brings us into the lives of the poor and suffering, revealing their extraordinary faith and courage in the direst of circumstances, and the tireless commitment of the doctors who work to address inequity one patient at a time. Listen on:www.mojo50.comiHeart RadioiTunesStreaming live via Youtube and Facebook:https://www.facebook.com/Therichsolution/

Neurosurgeon Dr. Aaron Berkowitz joins Lynn and Pete on The Mountain Life. Berkowitz takes it to heart that four billion people lack access to healthcare worldwide. He has written a book about his experiences including helping one man from Haiti with the largest brain tumor any of his medical colleagues had ever seen and the story that evolves from there. His new book is called ONE BY ONE BY ONE: Making a Small Difference Amid a Billion Problems .

Mike Chmielewski interviews neurologist Aaron Berkowitz about his new book One by One by One – Making a Small Difference Amid a Billion Problems https://www.radiofreepalmer.org/2020/06/11/author-interview-one-by-one-by-one-2020-6-11/feed/ 0

  Aaron Berkowitz has an outstanding history and experience as an entrepreneur. He has worked on his own - off and on - since he was 8 years old. His entrepreneurial and vagabond spirit, coupled with his childhood experiences, has been the driving force that makes him such a successful independent adjuster.   Aaron joins me today to share how his adjusting business has evolved since 2017 and why he’s now focused on improving his life and taking advantage of the time off between deployments. He shares how his childhood upbringing has impacted his career as an entrepreneur and the driving force that keeps him moving toward his goals. He also shares why he decided to stop using social media and explains why it’s critical for adjusters to identify what they want and take the necessary steps to achieve your goals.       “Define what you want. Until then, you will not go anywhere but in circles.” - Aaron Berkowitz       This week on Adjuster Talk:   How Aaron’s business has evolved since 2017 Why he is taking advantage of the slow periods between deployments How he maintains his health and fitness throughout his travels How his entrepreneurial spirit was sparked at such a young age The driving force that keeps him moving forward How he determines if he’s made successful strides toward his goals Why he decided to stop using social media and how it has impacted his personal and professional life The importance of identifying what you want and taking the necessary actions to achieve your goals     Resources Mentioned:   Living with the Monks: What Turning Off My Phone Taught Me about Happiness, Gratitude, and Focus by Jesse Itzler       Connect. Share. Inspire.   Thanks for tuning in to the Adjuster Talk podcast with your host, Jason Heenan! If you enjoyed today’s episode, please head over to iTunes to subscribe to the show and leave an honest review. You can also connect with us on Facebook, Twitter, Instagram, LinkedIn, and YouTube.

Aaron Berkowitz joins me once again on today’s episode of Adjuster Talk to share his insight, knowledge, and experience of working as an independent claims adjuster. On today’s episode, he shares tips on working with claims managers and what your goals as an adjuster should be – beyond the money. He also shares one of his earliest, and worst experiences as a claims adjuster just starting in the field and the lessons he has learned along the way to make his business successful and profitable.   “The smart adjuster doesn’t put pressure on their claims manager.” – Aaron Berkowitz   In This Episode of Adjuster Talk: Working with claims managers Evaluating expenses The pros and cons of being a firm owner What your “end-game” goals should really be as an adjuster Aaron’s definition of “hard work”   Resources: Weather Nation The Weather Channel Reed Timmer     Connect. Share. Inspire.             Thanks for tuning in to the Adjuster Talk podcast with your host, Jason Heenan! If you enjoyed today’s episode, please head over to iTunes to subscribe to the show and leave an honest review. You can also connect with us on Facebook, Twitter, Instagram, and YouTube.              If you’re interested in working with us, please feel free to email Jason at jheenan@royaladjustingservices.com or Mindy at mindy@royaladjustingservices.com with your resume to apply to be on our approved adjuster roster today!

Aaron Berkowitz is an independent catastrophe adjuster from Salinas, California. Aaron has been in the adjusting business since 2009 and he joins me on the show today to share his story on how he got started in the business, what keeps him motivated, and the secret to his success. We also discuss how social media and today’s technology has impacted the way property insurance adjusters work from day to day, how it differs from the way our older mentors ran their businesses, and the importance of staying prepared for inevitable weather related catastrophes nationwide.   “The preparedness doesn’t stop on any level.” – Aaron Berkowitz   In This Episode of Adjuster Talk: Staying excited about the job and how it helps keep you motivated Aaron’s scoping and claims writing strategy to help him make the most of his time How to develop a scoping and claims writing strategy that works for you at any skill or experience level How to get your first two claims when you’re just starting out Why being disciplined is critical in the adjusting industry How to be prepared for inevitable, weather-related catastrophes     Connect. Share. Inspire.           Thanks for tuning in to the Adjuster Talk podcast with your host, Jason Heenan! If you enjoyed today’s episode, please head over to iTunes to subscribe to the show and leave an honest review. You can also connect with us on Facebook, Twitter, Instagram, and YouTube.            If you’re interested in working with us, please feel free to email Jason at jheenan@royaladjustingservices.com or Mindy at mindy@royaladjustingservices.com with your resume to apply to be on our approved adjuster roster today!

In a return to a classic sports format, Jack Ulrich and I discuss this year's NBA-All Star Weekend and share our playoff predictions for the Eastern Conference. Later in the show Aaron Berkowitz and I talk about how the 2018 Olympics have gone so far, both in terms of the USA specifically and for the event as a whole.

Anne McElvoy and Lane Greene look at the current debate around creativity, and its value to our society. In this first episode, Anne tackles a Bach prelude with the help of pianist James Rhodes who believes that keyboard mastery is “just a physics problem”. Lane assesses how the brain behaves during periods of extreme creativity, and with the help of neuroscientist Aaron Berkowitz, considers how great creatives can de-activate parts of the brain to enhance performance. Concert pianist Di Wu considers the differing experiences of music teaching in China and the United States, and describes how she moved from conquering concertos to tackling business problems whilst studying for an MBA at Columbia University​ See acast.com/privacy for privacy and opt-out information.

Anne McElvoy and Lane Greene look at the current debate around creativity, and its value to our society. In this first episode, Anne tackles a Bach prelude with the help of pianist James Rhodes who believes that keyboard mastery is “just a physics problem”. Lane assesses how the brain behaves during periods of extreme creativity, and with the help of neuroscientist Aaron Berkowitz, considers how great creatives can de-activate parts of the brain to enhance performance. Concert pianist Di Wu considers the differing experiences of music teaching in China and the United States, and describes how she moved from conquering concertos to tackling business problems whilst studying for an MBA at Columbia University​ See acast.com/privacy for privacy and opt-out information.

Here is the 2nd Summer Special Podcast heading your way even though school isn't in session. This week Aaron Berkowitz and Isaac Weinberg joined me to have a lengthy discussion regarding the NBA and NFL. Hope you enjoy!

In the penultimate radio show of my junior year, Aaron Berkowitz joins me to discuss the biggest moves of the NFL Offseason, along with MLB predictions that are particularly targeted towards what's been going on with our slumping hometown Chicago Cubs! P.S. Our recording device briefly stopped working at around the 23 minute mark on the show, so my apologies for the random jump from Running Back to Wide Receiver talk.

1) Zika virus-associated Guillain-Barre Syndrome Variant in Haiti2 e-Pearl topic: Juvenile Huntington Disease3) Topic of the month: Clinical Trials Plenary Session at the AAN meeting about 5-HT6 antagonist as adjunctive therapy to cholinesterase inhibitors in patients with mild-to-moderate Alzheimer diseaseThis podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Stephen Donahue interviews Dr. Aaron Berkowitz about his paper on Zika virus-associated Guillain-Barre syndrome variant in Haiti. Dr. Ilena George is reading our e-Pearl of the week about juvenile Huntington disease. Dr. Alberto Espay interviews Dr. Alireza Atri about his Clinical Trials Plenary Session at the AAN meeting about 5-HT6 antagonist as adjunctive therapy to cholinesterase inhibitors in patients with mild-to-moderate Alzheimer disease.DISCLOSURES: Dr. Berkowitz receives royalties from the publication of the book: Clinical Pathophysiology Made Ridiculously Simple and the book: The Improvising Mind; received funding for travel from Stevens Institute of Technology; received speaker honorarium from Audio Digest; and received honorarium for recorded CME lecture.Dr. George serves on the editorial team for the Neurology® Resident and Fellow Section.Dr. Espay serves as Associate Editor for the Journal of Clinical Movement Disorders; serves as an editorial board member of Parkinsonism and Related Disorders and The European Neurological Journal; serves on the scientific advisory board for Solvay Pharmaceuticals, Inc. (now Abbvie), Chelsea Therapeutics International, Ltd., Teva Pharmaceutical Industries Ltd., Impax, Merz Pharmaceuticals, Inc., Pfizer Inc, Solstice Neurosciences, Eli Lilly and Company, ACADIA Pharmaceuticals, Inc. and USWorldMeds; is a consultant for Chelsea Therapeutics International, Ltd., Solvay Pharmaceuticals, Inc. (now Abbvie), ACADIA Pharmaceuticals, Inc., Cynapsus and Lundbeck, Inc; receives royalties for publications of books from Lippincott, Williams & Wilkins and Cambridge University Press; serves on the speakers' bureau of UCB, Teva Pharmaceutical Industries Ltd., American Academy of Neurology and Movement Disorders Society; receives research support from the CleveMed/Great Lake Neurotechnilogies, Michael J. Fox Foundation and the NIH.

Cerebral amyloid angiopathy-related inflammation and 2) Topic of the month: Neuro-infectious diseases. This podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Prachi Mehndiratta interviews Dr. Aaron Berkowitz about his paper on cerebral amyloid angiopathy-related inflammation. Dr. Adam Numis is reading our e-Pearl of the week about nasociliary reflex. In the next part of the podcast Dr. Chenjie Xia interviews Dr. Karen Roos about neurocysticercosis, its common manifestations, investigations and treatment. The participants had nothing to disclose except Drs. Numis and Roos.Dr. Berkowitz received speaker honoraria from Stevens Institute of Technology and receives royalties from the publications of the books Clinical Pathophysiology Made Ridiculously Simple, MedMaster and The Improvising Mind, Oxford.Dr. Numis serves on the editorial team for the Neurology® Resident and Fellow Section. Dr. Roos receives royalties for five published books.

Neurological symptoms occur in approximately 20% of patients with Sjögren's syndrome, and may be the presenting manifestations of the disease. In this podcast, PN co-editor Phil Smith asks Aaron Berkowitz, Department of Neurology, Brigham and Women's Hospital, Boston, about several neurological conditions that can occur in Sjögren's syndrome: sensory ganglionopathy, painful small fibre neuropathy, and transverse myelitis (independently or as part of neuromyelitis optica).Dr Berkowitz describes the symptoms, signs, differential diagnoses, recommended diagnostic evaluation, and treatment of each of these, highlighting the features that should alert neurologists to consider Sjögren's syndrome.Read the full review here: bit.ly/1fF2lev