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Guillain-Barré syndrome is a neurologic emergency with a broad range of clinical presentations that can make diagnosis challenging. In this episode, Dr. Mamatha Pasnoor reviews the classic features of Guillain-Barré syndrome, highlights important clinical variants and diagnostic red flags, and discusses how to interpret cerebrospinal fluid findings in atypical cases. She also shares practical guidance on treatment decisions, including the management of treatment-related fluctuations and distinguishing Guillain-Barré syndrome from chronic inflammatory neuropathies. In this episode, Aaron L. Berkowitz, MD, PhD, FAAN, speaks with Mamatha Pasnoor, MD, FAAN, author of the article "Guillain-Barré Syndrome" in the Continuum® October 2026 Peripheral Nerve and Motor Neuron Disorders issue. Dr. Berkowitz is a Continuum® Audio interviewer and a professor of neurology in the Department of Neurology at the University of California, San Francisco, in San Francisco, California. Dr. Pasnoor is a professor of neurology, program director of the neurology residency, and associate program director of the neuromuscular fellowship at the University of Kansas Medical Center in Kansas City, Kansas. Additional Resources Read the article: Guillain-Barré Syndrome 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. Berkowitz: When we learned about Guillain-Barré in medical school, we learned the classic presentation of a post-infectious acute ascending paralysis with areflexia. But Guillain-Barré is a syndrome that can have a large number of clinical variants, and much of what we learn about the classic presentation and diagnostic findings also has a lot of variation in clinical practice. I'm very excited today to talk with Dr. Mamatha Pasnoor, an expert in Guillain-Barré syndrome, about some of the large spectrum of clinical findings, CSF findings, and some of the exciting updates in treatment of this condition.   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. Mamatha Pasnoor about her article on Guillain-Barré syndrome. This article appears in the October 2026 Continuum issue on peripheral nerve and motor neuron disorders. Welcome to the podcast, Dr. Pasnoor, and would you please introduce yourself to our audience?   Dr. Pasnoor: Thank you, Dr. Berkowitz. I'm Mamatha Pasnoor. I'm from Kansas University. I'm a professor of neurology here, and I am the program director for neurology residency program and also the associate program director for neuromuscular diseases and fellowship. I'm also the medical advisor for GBS/CIDP Foundation International, and that's my area of interest in research and is autoimmune neuromuscular diseases, including CIDP and neuropathies and various other neuromuscular diseases, including myasthenia gravis.   Dr. Berkowitz: Fantastic. Well, I'm very excited to talk with you today. I really enjoyed reading your article. Lots of clinical pearls, very comprehensive and detailed review. I encourage our listeners to go ahead and look up your article and read it. We won't have time to even scratch the surface of all of the topics related to Guillain-Barré that you discussed in the article, but we will talk about some highlights and some things I certainly learned reading this. So, I imagine when many of us learned about Guillain-Barré in medical school or in residency, we learned the classic illness script of a post-infectious ascending paralysis and sensory symptoms with areflexia, albuminocytologic dissociation on CSF analysis, and usually demyelinating, but sometimes axonal features on nerve conduction studies. But as you review in the article, the clinical spectrum of this disease is really quite varied. The CSF can actually be normal or can show up pleocytosis. The nerve conduction studies can be normal, and the only more specific biomarker, the ganglioside antibodies, are only really associated with some variants, and even those are not always present. And in any case, you'll be waiting a long time for the results while the patient is in front of you with their acute illness. So today, I really want to focus our interview amongst the many topics you discuss in your excellent article on the spectrum of Guillain-Barré syndrome to make sure we know when should we be considering it, what's sort of atypical but fair game, what are some red flags that should lead us away from this diagnosis. So, let's begin with the clinical presentation. Could you talk to us a little bit about the classical presentation, the typical textbook presentation, and then some of the broad range of variants that can be seen under the umbrella of what we call Guillain-Barré syndrome?   Dr. Pasnoor: Yeah, that's a very good question. I think the 1st thing is all of us should recognize GBS because it is a neurological emergency, and usually the diagnosis is clinical. You really don't need any LP or spinal tap, MRI, or any of these to diagnose. It's mainly the progressive course is important of the patients. It should be a progressive less than 4 weeks, and if it's beyond 4 weeks, we are considering other conditions. It's symmetric weakness, and absent reflexes is one of the classic finding in this. And some of the patients may present with significant autonomic features, and some of them may present with respiratory problems. So that's very important for us to recognize early, you know, treat them early. So, this is the most common presentation of the GBS is progressive limb weakness, areflexia, and symptom progression less than 4 weeks. Some patients may have distal paresthesias. We talked about it. Numbness, as you mentioned. Ascending paralysis may start in the legs and goes up into the arms. Cranial nerve involvement may be seen, autonomic dysfunction and respiratory dysfunction may be seen in some of them. On the variants, basically this is the classic form, but the GBS, we need to identify the variants. The variants are like they can be paraparetic, that is like just involves the legs and arms distally, or they can involve the face, the pharyngeal-cervical-brachial variant. We see bifacial weakness of both the face and the limbs and paresthesias, pure sensory. These are all variants that we see. And other than that, we all remember from our earlier reading is, or learning is Miller Fisher variant and the variants associated that look like Miller Fisher, and we call them as Miller Fisher syndromes, which includes the typical and incomplete forms as well as Bickerstaff encephalitis into this category of the Miller Fisher variant syndrome.   Dr. Berkowitz: Thank you. Yeah, there's such a broad spectrum of variants. On the East Coast, when we see facial palsy, I trained and spent many years on the East Coast, in the summer, we always think about Lyme disease. And some cases even of bifacial palsy, we would think of Lyme disease. And some of those cases would turn out to be variant you mentioned bifacial weakness with acroparesthesias that on the East Coast might get mistaken for Lyme facial palsy with polyradiculitis. Any other variants that you've encountered or encountered in your reading and have your eye out for that are very atypical part of the spectrum?   Dr. Pasnoor: I think the motor GBS would be another, like, you have to keep that in mind. Because when we talk about classic GBS, we are talking about motor sensory, but then there can be a purely motor variant, and they can mimic many other conditions. I mean, especially you talked about, like, when they have facial involvement, you're thinking of, like, myasthenia gravis, you know, motor neuron disease. So, you need to think of these other conditions when you have a variant like motor GBS can be a variant that you're thinking of.   Dr. Berkowitz: Yeah. So pure motor, pure sensory, pure cranial nerves, pure ocular, and then struck reading your article and other articles I've read as I've encountered atypical cases that we ultimately thought were Guillain-Barre. Sometimes the patients keep their reflexes.   Dr. Pasnoor: The hyperreflexia in some cases of, AMAN, the motor variants, you do see some, and obviously in Bickerstaff's you have to remember that too. So, there could be some variants may come in with... Although we talk about this being areflexia, there sometimes can see hyperreflexia. Very rare. I wouldn't take that. That would be actually one of our red flags to say that this may not be GBS, because I know you brought this up earlier, which is very important for people to know, is there are some red flags that you think of when the GBS, when you're trying to see if this is GBS or some other condition is, like, if they have prominent bowel, bladder dysfunction at onset. I know these patients do have, people with GBS do have autonomic symptoms, but if you have a significant bladder, bowel involvement earlier on, or if they have fever, they have altered consciousness, these are red flags you have to think about. And obviously, if it's progressing beyond the 4 weeks, you think of other conditions. And the other thing is pleocytosis. We talked about LP. Although most of the patients, most of the people with GBS may not have high CSF protein in the 1st week,   Dr. Pasnoor: but majority of them convert to having high CSF protein in the 2nd week. About 90% may show that what we discuss abo

Inflammatory and autoimmune axonal neuropathies can cause rapidly progressive weakness, sensory loss, and pain, but recognizing treatable cases can be challenging. In this episode, Dr. Qihua Fan discusses key clinical patterns, diagnostic strategies, and common mimics of inflammatory axonal neuropathies, emphasizing the importance of careful follow-up and realistic treatment goals. Learn how electrodiagnostic studies, biomarkers, pathology, and emerging imaging techniques can help guide diagnosis, monitor disease activity, and assess treatment response. In this episode, Teshamae Monteith, MD, FAAN, speaks with Qihua Fan, MD, author of the article "Inflammatory and Autoimmune Axonal Neuropathies" in the Continuum® October 2026 Peripheral Nerve and Motor Neuron Disorders issue. Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida. Dr. Fan is a neuromuscular specialist, neuromuscular medicine fellowship director, and director of the ALS Clinic at Virginia Commonwealth University in Richmond, Virginia. Additional Resources Read the article: Inflammatory and Autoimmune Axonal Neuropathies 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: @headacheMD Full episode transcript available here Dr. Monteith: A patient presents with rapidly progressive weakness, sensory loss, and severe neuropathic pain. Is this an inflammatory neuropathy requiring urgent treatment, or a mimic that could lead to a misdiagnosis? Today, we'll discuss how to recognize inflammatory and autoimmune axonal neuropathies, navigate the diagnostic workup, and apply emerging advances in biomarkers, imaging, and treatment.   Dr. Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum. This exclusive Continuum audio interview is available only to you, our subscribers. After listening, you can get CME by going to continpub.com/audiocme. We hope you enjoy the interview.   Dr. Monteith: This is Dr. Teshamae Monteith. Today, I'm interviewing Dr. Qihua Fan about her article on inflammatory and autoimmune axonal neuropathies. This article appears in the October 2026 Continuum issue on peripheral nerve and motor neuron disorders. Welcome to our podcast. How are you?   Dr. Fan: Good. Thank you so much for having me.   Dr. Monteith: Please introduce yourself to our audience.   Dr. Fan: My name is Qihua Fan. I'm an Assistant Professor in Neuromuscular Medicine at Virginia Commonwealth University in Richmond, Virginia. It's nice to be here.   Dr. Monteith: And what got you interested in this field?   Dr. Fan: I was very lucky to meet a lot of brilliant thinkers along the way and a lot of really great role models. I was really blown away by how they're able to take a lot of different pieces of data. So, for example, meeting somebody in the emergency room and then doing their exam and doing their electrodiagnostics, then their pathology, and putting it all together and kind of seeing them from end-to-end care. They taught me how to think about things in a different way, and I've been hooked ever since.   Dr. Monteith: Cool. And so, what were the goals of your article?   Dr. Fan: The goals of this article was to try and pull out a couple of pearls in kind of approaching inflammatory axonal neuropathies. I think one of the trickiest things in axonal neuropathy management is we don't want to miss the treatable, reversible etiologies. But when we get it, it takes so much patience to not rush into judging whether or not we're successful, just because nerve recovery and axonal processes take such a long time. And so, we have to be used to kind of sitting there and waiting for 3 to 6 months to see if we're even on the right track. So, the biggest takeaway that I want folks to get out of this, is that stability is the goal in axonal inflammatory axonal neuropathies, and to be patient and to be creative about the modalities that we're using to see if our treatments are working.   Dr. Monteith: Why don't you help our listeners understand, as a group, how do you describe autoimmune axonal neuropathies?   Dr. Fan: So, a couple of principles in diagnosing and recognizing immune and inflammatory-mediated axonal neuropathies. One is that the tempo typically tends to be subacute. Number two, is you need to be able to recognize the typical patterns in which they'll present. So, the most common textbook one is the mononeuritis multiplex, subacute stepwise progression. That will coalesce over time into another pattern, asymmetric axonal polyneuropathy. A third pattern is sensory ataxia or sensory neuropathy or neuronopathy. And a fourth pattern is, it's a mouthful, it's radiculoplexus or plexus syndromes. So that will be similar to your diabetic amyotrophy. And then your exam electrodiagnostics should be working together to confirm that pattern. So, once you have that pattern recognized, then you're looking for labs, electrodiagnostics, pathology, and then treatment responsiveness to help support that hypothesis every step along the way.   Dr. Monteith: Why don't you tell us a little bit about some of the areas that you're most excited about in terms of latest developments in the field?   Dr. Fan: Yeah. So, I think a lot of us are seeing the role of neurofilament light chain entering into our practice, and I think this has been a huge game changer in the area of inflammatory axonal neuropathies in particular. I'll give an example. So, if we see a new vasculitic neuropathy, right, somebody who is dropping nerves left, right, and center, and you see a very precipitous decline, you want to do everything you can to try and stabilize that. But the most satisfying short-term thing that we can achieve in the past was just stability, so that they stop losing nerves, they stop progressing in terms of their weakness, stop progressing in terms of their sensory loss, but they still have a lot of pain, and it's very challenging to manage. But with the development and commercialization of neurofilament, we're able to kind of demonstrate a normalization in a very quantifiable way to say, "Hey, look, we were burning through nerve very quickly before, and now this is a data point that can help support our treatment decision to say, yes, we're on the right track."   Dr. Monteith: Great. Maybe you can speak a little bit more about the approach to the evaluation. I read in your article that two key areas is determining the subtype and then the extent of nerve injury.   Dr. Fan: Right. So, it's a little bit of pattern recognition, and we talk about four different common presentation patterns. The classic one that we get taught is the mononeuritis multiplex subacute stepwise progression. But a lot of times, once the inflammation has been there for long enough, we've picked off enough nerves that the pattern has coalesced into a more length-dependent pattern. Typically, there's a little bit of asymmetry, and so that's the second pattern, is an asymmetric sensory motor polyneuropathy. The third type is a sensory ataxia. Somebody's coming in, their balance is way off, they can't do fine motor tasks, but there's not much other cerebellar findings, but their sensory examination is shot. And then the fourth type is an LRPN. So, this is much more like your diabetic amyotrophy phenotype is, is one example, and a lot of times that will be monophasic. So those are kind of the four patterns that can commonly present as inflammatory axonal neuropathies.   Dr. Fan: Once you think that this might be inflammatory or axonal in etiology, you want to kind of gather data points and see if it's treatment responsive. And so, when you're thinking about autoimmune or inflammatory etiologies, you want to look for biomarkers, for example, pathology to say, "Yes, there are inflammatory infiltrates that are attacking the nerve." One of the most surprising and clinically important findings that I learned about this when I was a fellow, is that you can see inflammation on pathology in conditions that are not immune-mediated neuropathies. So, for example, even in diabetic neuropathy, you can find a dusting of perivascular inflammation on pathology, and that creates a very confusing interpretive picture because inflammation on biopsy doesn't automatically establish that this is an immune-driven problem or that immunotherapy will be helpful. So, the key takeaway is that the pathology alone is not enough. You still have to demonstrate that the disease is biologically active and that it's treatment responsive over time. So, you can confirm inflammatory neuropathy on pathology, but you need to show that you can alter the disease course, that it's treatment responsive, and you can't just go off of seeing inflammatory cells under a microscope.   Dr. Monteith: So how do you pivot away from that?   Dr. Fan: So that's why you have to build in multiple levels of confirmation. So, you have the pattern recognition to say, "Hey, I think this is, this might be an inflammatory neuropathy." Number two, I still look for the pathology for confirmation. I find it and then say, "Okay, if this is true inflammatory neuropathy, it should respond to treatment over time on exam, on biomarkers, on functional assessments, in the way that axonal neuropathy is expected to respond." So, you have to follow the exam over time, follow your biomarkers, and see if things are mapping out the way that you expect it to.   Dr. Monteith: Great. So, you gave some nice pearls in the article about ways to elicit temporal progression, and the extent of the disease. Can you talk a little bit about that so that someone who's in

Diabetic neuropathy is more than a disorder of numbness and pain in the feet. In this episode, Dr. Vera Fridman discusses diabetic neuropathy as a complex, multisystem condition, highlighting the importance of recognizing autonomic involvement, identifying high-risk patients early, and addressing factors that influence progression. Learn practical strategies for screening, prevention, symptom management, and recognizing when symptoms may suggest an alternative diagnosis. In this episode, Kait Nevel, MD, speaks with Vera Fridman, MD, author of the article "Diabetic Neuropathies" in the Continuum® October 2026 Peripheral Nerve and Motor Neuron Disorders issue. Dr. Nevel is a Continuum® Audio interviewer and a neurologist and neuro-oncologist at Indiana University School of Medicine in Indianapolis, Indiana. Dr. Fridman is an Associate Professor of Neurology and Neuromuscular Medicine Fellowship Director at the University of Colorado in Aurora, Colorado. Additional Resources Read the article: Diabetic Neuropathies 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: @IUneurodocmom Full episode transcript available here Dr. Nevel: Diabetic neuropathy affects millions of people, but in our neurology clinics, are we thinking about it too narrowly? In this clinic, Dr. Vera Fridman emphasizes that diabetic neuropathy is not simply a disease of the feet, revealing it instead as a complex neurologic syndrome with consequences that reach far beyond numbness and pain.   Dr. Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast.   Dr. Nevel: Hello, this is Dr. Kate Nevel. Today, I'm interviewing Dr. Vera Fridman about her article on diabetic neuropathies. This article appears in the October 2026 Continuum issue on peripheral nerve and motor neuron disorders. Vera, welcome to the podcast, and please introduce yourself to the audience.   Dr. Fridman: Hello, it's great to be here. I'm Vera Fridman, and I'm located at the University of Colorado Medical Center. I'm a neuromuscular neurologist with focus on neuropathy clinically and in my research, and it's great to join you.   Dr. Nevel: Wonderful. Looking forward to talking to you about your article and learning more. So, I always like to start these interviews with the question, what is the most important takeaway from your article for the practicing neurologist?   Dr. Fridman: I think to me, in thinking about this article and writing it, the most important message and take-home is that we need to start thinking about diabetes-associated nerve injury as a complex disorder that's multisystemic. So rather than sort of just focusing on the peripheral nerve involvement we're used to seeing at the bedside, to really start taking that early clinical presentation of numbness or tingling as a warning sign, as a heralding sign of something that is widespread, complex, systemic, the way we might think about other multi-organ systemic disorders.   Dr. Nevel: Great. And that leads me into my next question, because you really do emphasize that throughout your article, all the different ways that this kind of more systemic diabetic nerve injury can impact a person and affect their morbidity and even their mortality. So, can you tell us a little bit more about this more widespread diabetic nerve injury beyond the kind of classic diabetic peripheral neuropathy that maybe we think of as neurologists?   Dr. Fridman: Yeah, I think the idea here is that we have nerves innervating a lot of different organs, and they are also not siloed. They're interfacing with other parts of our biology, vasculature, you know, the impact of inflammation. All of these things are converging, and they are complicated. And so clinically, when I think about diabetic neuropathy associated with systemic injury, I think about cardiac autonomic neuropathy, about gastrointestinal and urogenital neuropathies, and that these symptoms can be really diverse, and they can be nebulous. And so, in seeing someone who just says, "I have a little bit of numbness and tingling in my toes," I think the clinician has to sort of force themselves to imagine that there's all this asymptomatic disruption in the person's presentation that they have to dig for to understand better.   Dr. Nevel: What else should we be asking to kind of delve deeper to investigate or identify a more widespread diabetic nerve injury?   Dr. Fridman: When I think about what sort of trainees and early clinicians miss, like when I see histories come from people who haven't been thinking about diabetic neuropathy for a long time, it's usually the autonomic that's missing. Do you have lightheadedness? Have you noticed decreased or increased sweating? Do you get full easily with meals, what we call early satiety? Patients don't know that word. Do you have sexual dysfunction? That's an enormously important question because it can actually herald that there's more widespread neuropathy, more severe neuropathy, and that there's autonomic involvement or potentially vascular involvement. So those are the ones that I see missed. And then the others would be related to the risk of ulceration. What is your foot care approach? Have you had ulcers in the past? I think a lot of people don't realize that having had an ulcer, even if it happened some time ago and healed, is a major risk factor for recurrent ulceration. You're going to pay attention differently to that patient. And then the other question that doesn't necessarily relate to symptoms, but I think is hugely important to ask is, what are your barriers to caring for your diabetes and for yourself? What is getting in the way of those preventative measures, which are really the only really reliable preventative things we can do, right? Like, we don't have good treatments for this disease. So why can't you exercise? What are some of the reasons why you can't? Really in a non-judgmental, guilt-free way, because we know diabetes increases the barrier to these things substantially, and that patients are struggling just to get through their day. So, I think understanding those obstacles early in the therapeutic relationship is where you can make the most impact.   Dr. Nevel: Thanks for sharing that. Can you tell us a little bit more about cardiac autonomic neuropathy and why that's so important?   Dr. Fridman: Yeah, well, it's important because basically the largest driver of mortality and cardiac death in this population. And I think sometimes even with well-managed diabetes, we are sort of heartbroken to see patients who have gone on to have really terrible outcomes from cardiac autonomic involvement that we didn't necessarily know was there. The other reason it's so important is because it stays asymptomatic for a very long time. So, it's one of these sort of elephant in the room entities that if you don't ask about, you don't look for intentionally, you're just not gonna know, and the patient's not gonna know. They're gonna think they're lightheaded from their medication, which is a very reasonable postulation when someone's taking neuropathic pain medications and blood sugar is going up and down. But it may just be that there's autonomic disease underlying. The other reason it's important is because it's difficult to test for. So even if you have the awareness that you have to think about it and ask about it, it's not always clear to clinicians what they're supposed to do next if those symptoms are there or how to evaluate them. And so, I think for all those reasons, it's probably the most undetected complication, and it's hugely common, and in some cases preventable through aggressive management of disease. So, I think for all those reasons, it comes out as the one that we need to remind ourselves about.   Dr. Nevel: How do you evaluate for cardiac autonomic neuropathy in your clinic?   Dr. Fridman: That's a great question. I think I start really with the questions that will be included in this article of kind of these detailed questions about symptoms that they may not know come together as indicating autonomic disease. Then at the bedside, I do a quick heart rate screen to see if they have resting tachycardia. Unfortunately, resting tachycardia is a late manifestation of cardiac autonomic neuropathy, so once you see it, it's probably too late. The next thing is to just perform orthostatic vital signs in the clinic and trying to get in the habit of having the patient lying and sitting and standing and taking the time. And in a busy clinic, that's actually quite a big ask. But if you can get a medical assistant trained and ready to do it on most patients, that I think is really important. If I'm concerned about it, then an EKG, which obviously wouldn't necessarily happen in the same visit, can help look for heart rate variability. And then the next layer is really talking to their primary care about a cardiology referral, because at that point, I think neurologists need help. And that's the other, I think, salient message from my thinking about this field is that this is not something that one practitioner can take on alone, and there has to be a really strong multidisciplinary network, just like we would do for our other complex disorders.   Dr. Nevel: Yeah. Do you see in the future there being more multidisciplinary engagement between neurology and cardiology for these patients if this is such a difficult to diagnose problem, but big cause of mortality in these patients?   Dr. Fri

Neuropathy can present in many ways beyond the classic pattern of numbness and tingling. In this episode, Dr. Reza Seyedsadjadi discusses a practical diagnostic approach, highlighting key clinical clues, electrodiagnostic findings, and the role of genetic testing and other specialized studies in identifying common and uncommon causes of neuropathy. In this episode, Casey S. Albin, MD, FAAN, speaks with Reza Sadjadi, MD, author of the article "The Diagnostic Approach to Neuropathy" in the Continuum® October 2026 Peripheral Nerve and Motor Neuron Disorders issue. Dr. Albin is a Continuum® Audio interviewer, associate editor of media engagement, and an assistant professor of neurology and neurosurgery at Emory University School of Medicine in Atlanta, Georgia. Dr. Sadjadi is an assistant professor of neurology at Harvard Medical School and Massachusetts General Hospital in Boston, Massachusetts. Additional Resources Read the article: The Diagnostic Approach to Neuropathy 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: @caseyalbin Full episode transcript available here Dr. Albin: The patient comes into your office with numbness and tingling, and it seems like it's probably a pretty straightforward neuropathy. But what about if it's not? Or what if the EMG and nerve conduction studies suggest something else? What if the patient is giving you extra clues about other symptoms where they feel ataxic or have systemic complications as well? All of those things may be part of a neuropathic picture. And today, we are so fortunate to talk to Dr. Seyedsadjadi about just this.   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. Albin: Hi, all. This is Dr. Casey Albin. Today, I'm interviewing Dr. Reza Seyedsadjadi about his article on the diagnostic approach to neuropathy. This article appears in the October 2026 Continuum issue on peripheral nerve and motor neuron disorders. Welcome to the podcast. I'm so excited to have you here, Dr. Seyedsadjadi. Just love for you to tell us a little bit about yourself and your background and how you got interested in this topic.   Dr. Seyedsadjadi: Hi. Thank you for the kind invitation and the opportunity to contribute to the Continuum. I'm a neuromuscular neurologist. I work here at Mass General Hospital. I got interested in peripheral nerve disease throughout my early training in neurology and continued with the fellowship in neuromuscular disorders, and I've been seeing patients with mostly neuropathy, inherited and acquired neuropathies here in Mass General Hospital.   Dr. Albin: Excellent. And so, you are the perfect person to write this intro article. And so, I always like to start with the basics. The patient comes to you. What are some of the symptoms that you're listening for that help you clue in that this is probably a neuropathy, not somewhere else in the peripheral nerve system?   Dr. Seyedsadjadi: What an excellent question. And it is still difficult to 100% be sure, but overall, I like to put things in different buckets to help you have a pattern recognition with what you think that makes sense to be a neuropathy, a neuronopathy, a radiculopathy. In general, I divide things into positive and negative sensory symptoms in terms of complaints. Positive ones like hyperesthesia, paresthesia, burning, tingling sensation. Negative sensory symptoms are a little bit more tricky, loss of sensation, balance issues. When somebody comes, you have to listen to all of these symptoms in conjunction with the distribution of the symptoms, how they evolve over time, to give you a clue whether this is a neuropathy or just neuropathic symptom related to a different process that could mimic neuropathy. And sometimes it would be difficult to delineate between the two, especially if a patient is very complex, has two different processes going on. But first off, it's good to know if you have positive sensory symptoms, it is more likely that this is a peripheral process than negative sensory symptoms. And some other features that we usually overlook when we see the patient in the clinical setting, especially if it's busy, those are the autonomic complaints that we can talk more about.   Dr. Albin: Yes. And I really wanna double-click on a lot of these features that you brought up. So, I'm hearing you're thinking about not only the symptom quality, but also that pattern of distribution. What about that sort of localized pattern of distribution?   Dr. Seyedsadjadi: Yeah. So typically, the general teaching is that nerves are very long in terms of the course, and when the damage happens to the nerve, the pattern would be a length-dependent pattern, meaning the longest nerve or the tip of the longest nerve will be affected, and this will gradually affect and go more proximally in a symmetrical pattern in more common known types of neuropathy. That's not always true. Sometimes you can have a non-length dependent neuropathy. You can have like an asymmetric neuropathy. But these are all small clues that you can use to see, to help you to narrow your differential diagnosis. So, you can have like a vasculitic neuropathy, which is necessarily not a length-dependent process. It affects one side, not necessarily the other side, and the progression of it, which could be stepwise rather than gradual progression of the disease.   Dr. Albin: I love that. Thinking not only just about the typical numbness and tingling in your fingers and toes, but recognizing that while that is a very common pattern of neuropathic symptoms, that you may have a patchy distribution and that you can still put neuropathy on your differential, even if it's asymmetric and even if it's not starting at tips of the fingers and tips of the toes.   Dr. Seyedsadjadi: Exactly. Nicely summarized.   Dr. Albin: One of the points that I really took away from your article was how sensory symptoms or motor symptoms, whether there's a predominance of one or the other, that actually may have some real importance in helping you think through the underlying process. So, can you tell us a little bit more about that?   Dr. Seyedsadjadi: Exactly. And also, I don't want to confuse this with necessarily involvement of sensory nerves because you can also have positive sensory and negative sensory symptoms. But looking at the signs in terms of how patients present- If you have predominance of, like, motor weakness, you have a patient who comes with the distal upper and lower extremity weakness, but sensory symptoms more than signs, are relatively milder. Obviously, you think more about process that is more chronic, affecting motor nerves more than sensory nerves, or equally at least, you think about more hereditary cases. Whereas when you have more sensory symptoms or predominance of sensory symptoms and less of motor involvement and more recent presentation, you think about more acquired causes of neuropathy. Now, that is not universal because we know that there are acquired neuropathies that affect the motor nerves more than sensory nerves, and we have hereditary neuropathies that purely affect sensory nerves like CANVAS syndrome. But in general, it's good to have, like, a pattern recognition. Now you can more comfortably look for those outliers that would be like a framework that you can approach them by looking for subtle signs and differences that they have from them.   Dr. Albin: I think that's so true of most of what we deal with in neurology. Like, most of neurology is being able to recognize the 75% to 80% that present in the normal typical pattern. But it's learning that for every localization within neurology, there are those variants. They don't read the textbook. But I do love that how if you're thinking about more sensory symptoms and more recent onset, you're generally thinking this is acquired versus that motor really standing out above and beyond the sensory symptoms, thinking more, "Hmm, could this be a hereditary? Should I look a little bit further into the family history?" Great point. And then I heard, especially in our first opening statement, it can be really hard to screen for autonomic symptoms, but that is really a hallmark of neuropathies because the autonomic nervous system is also composed of nerves. So, in a busy clinical environment, how do you suss this out, and what are you asking patients about?   Dr. Seyedsadjadi: It's a great question, I don't think you can never be perfect on that because as you said, in order to do the justice, you really have to go through all systems. One way is to use some of the outcome measures that autonomic symptoms you can ask the patient sort of in ahead of the time. But there are some questions that are more important, and it is difficult to get them from patients if you don't really ask them. And sometimes we shy away for different reasons from those questions. Some of these could be related to the function of the bowel and bladder, erectile dysfunction, specific questions about orthostasis, IBS-like symptoms, early satiety, and some overlap syndrome symptoms like dry eyes and dry mouth could indicate different things. These are the main categories of the questions that you ask. And when you start asking these questions, sometimes patients start adding symptoms, "Oh, I don't have this, but I also have, like, some other dysmotility issue." So, that comes up.   Dr. Albin: Absolutely, because these are symptoms that the patient may not put

In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Noah A. Kolb, MD, who served as the guest editor of the October 2026 Peripheral Nerve and Motor Neuron Disorders issue. They provide a preview of the issue, which publishes on October 2, 2026. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Kolb is a professor of neurological sciences at the Robert Larner College of Medicine at the University of Vermont in Burlington, Vermont. Additional Resources Read the issue: continuum.aan.com Subscribe to Continuum®: shop.lww.com/Continuum 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: @LyellJ Full episode transcript available here Dr. Jones: The human brain is incredibly complex. That's one of the reasons we like to study it and care for patients with neurologic problems. But to translate cognition into action, we need a functioning sensorimotor and autonomic peripheral nervous system. What do we do when those peripheral systems aren't working? Today, we're speaking with Dr. Noah Kolb, guest editor of our latest issue of Continuum on peripheral nerve and motor neuron disorders.   Dr. Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about subscribing to the journal, listening to verbatim recordings of the articles, and exclusive access to interviews not featured on the podcast.   Dr. Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today, I'm interviewing Dr. Noah Kolb, who is Continuum's guest editor for our latest issue on peripheral nerve and motor neuron disorders. Dr. Kolb is a professor of neurology at the University of Vermont Larner College of Medicine in Burlington, Vermont, where he specializes in the care of patients with neuromuscular disorders, including patients with peripheral neuropathy and other immune-mediated neuromuscular diseases. Dr. Kolb, welcome. Thank you for joining us today. Why don't you introduce yourself to our listeners?   Dr. Kolb: Well, thank you very much for having me. Please call me Noah. I've been a longtime listener of Continuum, dating all the way back to when they came on CDs, so it's really a pleasure to be here. Like you said, I'm a neuromuscular doctor up in Vermont. I take care of the whole scope of neuromuscular disease, but kind of wear 3 different hats. I focus my research primarily in chemotherapy-induced neuropathy, but also do other diseases as well. Obviously, see patients clinically, and then I'm an educator as well, so I run the neurology clerkship and the acting AIs for the medical school. So, it's a fun job.   Dr. Jones: Well, thanks for sharing that little bit of history on Continuum Audio, Noah. I got to be honest with you, I don't know if I've ever seen a Continuum Audio CD. If anybody out there in the audience has a Continuum Audio CD, post a picture online and we'll like and share it. I wonder how many of those are still out there. I really appreciate you not just joining us today, Noah, but also putting together this really stellar issue, a very timely update and overview of peripheral nerve and motor neuron disorders. A lot of good topics for us to dig into today. What I'm going to do before we get into questions is ask our audience Continuum Audio's trivia question. Dr. Kolb and I were talking about this before we started recording here. So, the trivia question, just to frame it up a little bit, the transthyretin or TTR protein receives a lot of attention in neuromuscular medicine as the protein behind the most common causes of acquired and familial amyloidosis. But transthyretin is known in clinical settings by a different name and checked for an entirely different reason. So, the trivia question is, what is the other common name for transthyretin? Stick around, and we'll share the answer at the end of our interview. So, let's get right to it. Our listeners know that peripheral neuropathy is common, right? It affects 2 to 3 percent of the general population and 6 to 7 percent of patients who are older than 60. In your mind, Noah, what's the main thing you would like clinicians to know or do differently in the care of these patients?   Dr. Kolb: Yeah, that's a great question. I think it's something that we spend a lot of time teaching our residents and working with our fellows about is understanding the right workup for people presenting with neuropathy because it's very easy to overdo it with more labs and a broader workup than you need. So, when somebody presents with sort of a garden variety neuropathy that doesn't have red flags, the important things to order in terms of a workup are hemoglobin A1C, B12, and SPEP with IFE, potentially serum light chains, and some thyroid studies as well. Because those are really the most common reasons, and then to make sure that they ask the most important historical questions, like about alcohol use, et cetera. If you're going to find a cause for neuropathy, particularly if it's slowly progressive and sensory predominant, oftentimes the answer is found right in that basic workup.   Dr. Jones: Got it. And I think that's very well taken. And I think one of the questions that commonly comes up in the neuromuscular, but also in the broader neurology setting is, when you're evaluating a patient, especially an older patient who has a new onset length-dependent sensorimotor peripheral neuropathy, you've identified the neuropathy, and you're starting to consider what are those potential underlying disorders or risk factors that that neuropathy could be a warning sign of, right? So, you look for metabolic disease, B12 deficiency, paraproteinemia, et cetera. Where do you stop? In what settings do you do more expanded evaluations, genetic testing, et cetera?   Dr. Kolb: Yeah, and I think this kind of goes back a little bit to the last question where the primary focus of the workup that we do is driven by the most common causes. That's why hemoglobin A1C is so important. And so, thinking through what is likely to be the cause in the specific patient setting is kind of really critical. And again, if you don't have red flags, then the labs that we mentioned previously are probably sufficient in terms of a workup. But if there are any of the other red flags, it's really important specifically because there may be treatable causes of neuropathy or things that would affect the prognosis that'd be important to understand earlier so we can make sure we either engage the right therapies or do a broader diagnostic workup. An important part of that is understanding when to use EMG nerve conduction studies and when not to. So obviously, as a neuromuscular doc who does EMGs, I'm very fond of them. But we regularly see patients in our lab who perhaps don't need one. If somebody has a sensory predominant, slowly progressive neuropathy, particularly if you have an etiology, those patients usually don't need an EMG nerve conduction study. When it's asymmetric, when there's prominent weakness, when there's a lot of autonomic symptoms, those are the times when it can be a lot more informative and helpful to try to get an EMG nerve conduction study to see if we can get at what the underlying etiology is.   Dr. Jones: That's very helpful, Noah. Thank you. And so, let's think about a scenario that I think many of our listeners may have encountered in their practice. You're seeing a patient who has a somewhat rapidly progressive, painful neuropathy, which has some small fiber characteristics. They've got a little bit of autonomic dysfunction, and you worry about the possibility of amyloidosis. How do you approach that evaluation and treatment, and why is it important to think about that diagnosis?   Dr. Kolb: Yeah, that's great. It's important to think about that diagnosis because we now have good treatments for AL amyloid and for ATTR-based amyloid. So, because these are treatable disorders, it's really critical that you identify them. And the reality is it's not always straightforward making a diagnosis of amyloid. As you would with any other type of neuropathy, the workup is gonna begin with serum free light chains, SPEP, trying to see if there are any monoclonal gammopathies or elevation in light chains. But importantly, you need to think about what the next diagnostic steps are and understanding how likely those tests are to be abnormal in the setting of amyloid is important as well, because the easier to obtain tests don't have perfect sensitivity. So, once you've moved on kind of from the basic labs, we think about a fat aspirate or a skin biopsy to look and see if there's any evidence of amyloid. But if your clinical suspicion is high enough, it's important to move to a sural nerve biopsy and genetic testing. That's really the best way to confirm this diagnosis.   Dr. Jones: Very helpful. And obviously, that's not just academic, as it might have been at one point. This is something that we now have good disease-modifying therapies for, which leads to another question that I think our listeners may encounter in their practice. When you think about all the available gene tests in panels and other genomic tools that we have to investigate patients, when do you do a broad genetic evaluation for patients with neuropathy?   Dr. Kolb: Yeah, it's a good question. It depends partly on specifically what we're looking for. I think that as with many things in neurology, one of the reasons I got interested in it, and many people did, is we like doing detective work, and the history often lies in the examination and in our clinical history at the bedside. And for that reason