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
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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 about albuminocytologic dissociation. But if you look at it, pleocytosis, what is the cutoff of considering a pleocytosis? That's also important, I think. Some people, even up to 50 cells per cubic millimeter, we are thinking of still GBS, you know, so less than that. But if you're having more than that, think of other conditions rather than thinking of GBS.
Dr. Berkowitz: Fantastic. Yeah, there's a lot of great pearls there that I want to discuss with you. Yeah, we talked about the very broad spectrum and that Guillain-Barre can really be in the differential diagnosis for a lot of presentations, whether motor, sensory, multiple cranial neuropathies, ataxia, some combination of these features. And you started to get into another area I want to talk to you more about, which is some of the red flags. Let's talk a little bit about clinical. You mentioned prominent bowel or bladder. Again, it would be very, very atypical to have the sphincter involvement in Guillain-Barre, right? We said you could, just in the spirit of talking about the spectrum of variance, but if there was prominent bowel or bladder and setting up otherwise ascending, quote-unquote, "paralysis sensory loss", where would that point you to as far as diagnosis and workup?
Dr. Pasnoor: I would think more of a spinal cord lesion more than anything else. So always make sure that they do not have, like, transverse myelitis or, you know, other bowel. I think a spinal cord would be my 1st inclination to look at.
Dr. Berkowitz: Yeah, that's a great point. Yeah, I remember one of my mentors telling me about a case that looked a lot like Guillain-Barre and had areflexia, and it was actually an epidural abscess. And of course, with spinal shock, there's absent reflexes. So acute spinal cord versus acute polyneuropathy can be tricky to distinguish. You also mentioned something you discuss in the article that is the rate of progression. So you mentioned Guillain-Barre is usually going to nadir around 2 to 4 weeks, and you mentioned one red flag is if the disease keeps progressing beyond 4 weeks. What sorts of things enter into your differential diagnosis for something that begins looking clinically like Guillain-Barre syndrome, maybe even has CSF findings suggestive of Guillain-
Barre, we'll talk more about CSF in a moment, but continues to progress beyond 4 weeks. What sorts of things do you think about there?
Dr. Pasnoor: Yeah, I mean, the 1st important thing is why do we even care about, like, you know, beyond 4 weeks? That's important for us because of the management varies with beyond 4 weeks in this condition. So, if you're thinking of GBS, but it looks like a demyelinating process, and if it is progressing beyond 4 weeks, then you're thinking coming into subacute form of this or even chronic, that is CIDP, that's again, the treatments vary with the CIDP versus GBS. And then also looking at treatment-related fluctuations, sometimes we see that, you know, they get better. The treatments again have worsening again. Or the other thing we are also looking at, could this be like an acute onset CIDP if they have more than 3 episodes within the 1st 8 weeks? You know, you're thinking of, again, acute onset CIDP. That's also important to be able to identify earlier on and diagnose them so that you can treat them in the right way.
Dr. Berkowitz: Perfect. We talked about bowel, bladder as a red flag in a patient otherwise presenting with symmetric, rapidly progressive sensory motor dysfunction. You mentioned the time course. In the beginning, we won't know when it's week one, week 2, week 3, but condition that continues to progress or fluctuate significantly beyond 4 weeks, start thinking more about CIDP spectrum, subacute inflammatory neuropathy type conditions. Any other clinical red flags before we talk about the CSF to alert our listeners to beyond bowel, bladder, and then the sort of progression beyond 4 weeks or fluctuation beyond 4 weeks?
Dr. Pasnoor: I think, uh, we talked, briefly about upper motor neuron signs. You know, that's definitely another red flag is if they have brisk reflexes. You know, again, there's a few variants that can have that, but if they have increased tone, brisk reflexes, like upper motor neuron signs, then you need to think of other conditions too, rather than GBS. Obviously, like central signs like, being uncoor-- or, uh, decreased level of consciousness, that would be another red flag for us.
Dr. Berkowitz: Perfect. And as you mentioned before, each of these red flags sort of has exceptions on the other side, right, that the Bickerstaff variant does have cephalopathy and can have upper motor neuron signs, but again, highly atypical, very rare syndrome, right? So, it, so it would push us away. Great. And you started to mention this a little bit earlier, but those are some important clinical red flags, and we should question the diagnosis of Guillain-Barre. What about CSF findings? You mentioned we could see up to 50 cells, but you might start to wonder if you have the right diagnosis here. You also mentioned the CSF can be normal, even though every board's question, right, it's gonna be GBS, the, there'll be albuminocytologic dissociation. Can you talk a little bit about CSF findings, what's acceptable and fair game, um, to still call it GBS, and what are things where you'd say it may still be, but we really need to look into other diagnoses, or things where you say, "No, no, no. This CSF is not compatible with a diagnosis of GBS."
Dr. Pasnoor: One is, like I mentioned earlier, if the CSF is drawn, like if we, if we get the CSF very early on, like within the first week, it can be normal. So normal does not, uh, rule out GBS in that case. That's why this, as we know, this is a supportive evidence. It's not a primary, uh, for diagnostic, for diagnosis of GBS. So, we need to make sure that with, if it is within one week, it may be normal. And if it is beyond that, usually majority of
the patients, more than 90 percent may, uh, show the albuminocytologic dissociation, which we are talking about, like cells may be normal, but the protein is high. What is high protein, again, it varies also with age, so we have to remember that, you know, again, with age it may vary. And also, someone who has diabetes can-- you're looking for a higher protein compared to the normal, um, other patients who not, who are not diabetic. And the number of cells, they-- in, in previous studies, uh, we have seen even up to 50 cells per millimeter, which is, I think is pretty high. But, uh, you know, again, if, if it's more than 50, definitely you need to think of other conditions. But if it is up to that, then you look at the clinical scenario and, uh, like o-obviously, if the patient has fever, uh, you can still think about other conditions like, uh, other infectious conditions. But if it is more than 50 cells per cubic millimeter, uh, definitely think of non-GBS conditions.
Dr. Berkowitz: Yeah. So again, like the clinical picture, right, such a broad range, and you discussed this in your article, broad range of CSF findings from normal to somewhat cellular, right? Maybe you'd see 6, 7, less than 10 cells, and you'd say the clinical picture fits. It's still dissociation, right? The protein is high, the, the cells. But gee, 20, 30, 40, 50 cells, I would be pretty uncomfortable, right?
Dr. Pasnoor: I agree with you. I think, uh, once it gets above 10, I think I get a little uncomfortable with that. I definitely wanna, like, make sure there's no other cause for that. Although we, we say it's up to 50, but, you know, I would still look for other causes if it is beyond 10.
Dr. Berkowitz: Um, for completeness in our discussion here, what are some of the other things you would be looking for when you see what looks like Guillain-Barre syndrome? It appears to be peripheral, it's rapidly progressive, and yet you're surprised on the CSF to find 45, 46, up to 50 cells. What are the things that you want to evaluate for a rule out, um, when you see that red flag of high cell count?
Dr. Pasnoor: I would definitely look for any infiltrative or infective cause. Like, if it's an elderly patient, you're looking at could this be lymphoma or some kind of infiltrative, like, malignancy or an infectious process. Like, again, there is, uh, like West Nile virus, you know, that's another thing that we think of in, patients, with the motor presentation specifically, like may see West Nile virus. So, there's infective or infla- uh, inflamm-, I would be more worried about those conditions.
Dr. Berkowitz: That's very helpful. Okay, we've spent most of our interview talking about the clinical spectrum and CSF spectrum, and those were areas you focused on in your paper with lots of pearls that I thought would be helpful for our listeners to hear more about. In our final moments here, let's talk briefly about treatment. Again, there's a lot more on treatment in your article we won't have time to get to today. I think all our listeners are familiar, right, with the, the sort of mainstay of treatment being either IVIG or plasma exchange along with intensive supportive care. Given that this is a disease, as you mentioned, that can have respiratory complications, autonomic complications, and all the complications that can come along with a neuromuscular emergency and critical illness. One question that often comes up in practice, and I was so glad to see addressed in your paper, is what to do when the patient doesn't respond to treatment. You 1st point out the important clinical pearl that something I also like to teach our
residents that when you give IVIG or plasma exchange, it's not like the patient gets better immediately, right? I think of it as you're sort of putting out the fire of inflammation, but the myelin still has to grow back. But there are some patients who even you wait a few weeks, they're really not getting better, or they seem to improve and they get worse, what are called treatment-related fluctuations. What does the literature tell us about how we should be treating these patients? Should a patient who doesn't improve get another round of IVIG or another round of plasma exchange, or a mix of IVIG and plasma exchange, or plasma exchange and IVIG? If they fluctuate, is that different than if they just don't get better? How do you approach these dilemmas after you've done the initial treatment and the patient is still not improving or continuing to kind of fluctuate in their clinical status?
Dr. Pasnoor: Yeah, that's a great question, actually. So, if you look at... I mean, these patients can be varied presentation. Some people may come in with, like, severe disease, and they may not improve right away with the treatments. And one of the things that I teach our residents is that we need to wait. You know, in some cases they do. Once we give the treatment and they are either plateaued or, like, stabilized, you know, we just, we have to wait and continue with the supportive treatment like physical therapy or multidisciplinary care. We do that. So, we do not routinely do, like, corticosteroids or 2nd course of IVIG. There's no benefit with 2nd course of IVIG, in the patients normally. And in fact, actually giving another IVIG, there's more risk than benefits, and you'll see that in the article. And, uh, sequential PLEX followed by, immediately by IVIG has also not been... This hasn't shown much difference. One of the things that we need to make sure when you have a patient who comes in with not responding to treatment or is continuing to progress is making sure that this is not CIDP. And again, when we talked about fluctuations, the treatment-related fluctuations are a little different from acute onset CIDP. So, identifying that is very important because, again, if it's CIDP, like acute onset CIDP, the treatment varies. There, we are thinking of corticosteroids and other treatments, whereas if you're thinking of, treatment-related fluctuations, again, we usually don't... I mean, in general, like for GBS, we, we are not treating another treatment. And whether you use IVIG or plasma exchange, both are equally effective treatment options for these patients.
Dr. Berkowitz: So, that's helpful. So, if the patient has not gotten better, there's been no fluctuation, obviously we need to wait. But if you've waited and it's still not getting better at all, and you're convinced you have the right diagnosis, really no evidence for retreatment or mixing and matching IVIG, plasma exchange. But for these patients who appear to be getting better after their nadir and then decline again, and as you mentioned, this could be suggestion of CIDP, but if it's just one or 2 fluctuations, not a lot of fluctuations over a more subacute time course, those are patients that I understand that you would consider retreatment. Yeah. Okay. Um, good. And there's a lot more discussion of this in the literature that backs it up, but I thought of the treatment topics, those were some of the ones that are most challenging in practice and the data on them relatively recent, right? The, the repeat treatment, I think, relatively recent in the past few years that paper was published on that. Yeah. I learned a lot from that, as I did from the rest of your article and from talking to you today. So again, today I've been interviewing Dr. Mamatha Pasnoor about her article on Guillain-Barre syndrome. The article appears in the October 2026 Continuum issue on peripheral nerve and motor neuron disorders. 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. Pasnoor: Thank you all for listening today.
Dr. Monteith: This is Dr. Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audiocme. Thank you for listening to Continuum Audio.