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
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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 the ER at the bedside, we can get a bigger sense of the problem?
Dr. Fan: Sure. I think it's very helpful to kind of nail it down in two different ways. One is kind of starting from where we are and working our way backwards. So, if I'm seeing them in the emergency room, or if I'm seeing them in the clinic and they're coming in with a gait aid of some sort, right, they're coming in with a walker, they might not always have walked with a walker. So how long have you been needing to use a walker for? Were you using a cane before that? And so, that kind of gives you discrete moments in time to help build a case of, when did this walking problem start, for example. You can use the same concept for other aspects of their function. So, if they're not able to type or if they're not able to play the piano the way they used to, you know, how long has that been going on for? The limitation is that it doesn't distinguish very well between sensory deficits or motor deficits, but at least that gives you a timeline. The other thing I'll add for the exam is not only do we have to establish whether or not there's a deficit, but we also have to establish a very reproducible and reliable baseline so that as we're seeing them back in a couple of months, in a year, we have very reliable data to look back at and say, "Okay, is the exam worse? Is their nerve function worse, or are they stable, or are they even doing better and starting to recover?"
Dr. Monteith: And speaking of exam, what are some barriers to the evaluation, and what are some ways to mitigate those barriers?
Dr. Fan: I think the trickiest part, especially in neuropathies, is sensory exam is very, very difficult and very difficult to quantify. A couple of the ways that I've found to be helpful in being consistent and having a reproducible exam is trying to keep it as clear and dichotomous as possible. So, rather than asking somebody, "Does this feel as sharp on your toe as it does on your shin?" That can lead to patients not being able to describe what they're feeling very well. They're wanting to be helpful, and the way that they describe things will change over time, even if it's the same type of sensation. So, one
way that I try to keep it as simple and clear as possible is, can you feel the difference between sharp versus dull? And we'll test with their eyes closed, the pointy side of a safety pin and say, "Can you tell, tell me if this is sharp or dull?" And if they can distinguish, then at least we have that to go off of. And same thing for vibration, right? If they have paresthesias and they can't tell me the difference between vibration or no vibration at the toes, that's something that is reproducible, demonstrable over time. It doesn't give the nuance that a lot of patients would like to give you in qualitative characteristics, but at least you have something very, very clear to go back on in 6 months or a year.
Dr. Monteith: And what are some mimics that we should consider when thinking about the differential diagnosis, or what are certain conditions that could lead to a misdiagnosis?
Dr. Fan: The differentials will depend on the presenting phenotype, and so that's why it's really important to figure out which pattern are you starting off with. So, for example, if it's a mononeuritis multiplex pattern, stepwise progression picking off individual nerves, you wanna make sure it's not something hereditary, right, like HNPP. If it's a rapidly progressive asymmetric sensorimotor neuropathy, again, you wanna make sure that it's not something hereditary, or atypical hereditary, like TTR or amyloid neuropathy. If it's a sensory ataxia, you can have metabolic or toxic etiologies like B6 toxicity or platinum exposure that can progress quite rapidly. And then for your LRPN syndromes, you wanna make sure that it's not something infiltrative like a hematoma or a tumor that's causing this picture. So, it really, really depends on the initial presenting phenotype, the pattern of presentation, and then you can kind of figure out your differentials from there.
Dr. Monteith: Can you remind us what some of the hallmarks are of the electrodiagnostic testing?
Dr. Fan: Yeah. So, the things that you're looking for are asymmetry from side to side. Electrodiagnostics should confirm that there is a sensory motor or sensory polyneuropathy. The red flags that you're looking for on EMG to say that this is not just a garden variety type of neuropathy, is that there is a very significant asymmetry from side to side. So, you want to increase the yield by testing the affected limbs and the affected parts of the body, and then compare to the other side and see, is there a marked asymmetry or not? I'll take an example of vasculitic neuropathy again. So, if you catch something that was recently, very recently affected and you do the exam too soon, the Wallerian degeneration hasn't had time to manifest yet on electrodiagnostics, and so it could show up as a pseudoconduction block. If you stimulate above the lesion and the lesion below, it looks like the signal's just not traveling well through that one segment. And so, then it's important to kind of put everything into context and look at your whole clinical picture and say, "Well, could this be a pseudoconduction block? Are things evolving the way I would expect a demyelinating neuropathy to do, or is this something that might be early axonal neuropathy and come back?" If you feel like my exam's not matching up, my data points aren't matching up, my lab values aren't matching up, am I missing something? And then come back and retest again to see if it's really axonal.
Dr. Monteith: Can you speak a little bit more about your approach to follow-up? You mentioned key points like stability, but also making sure that you've identified early anything that might possibly be reversible, but then also not repeating electrodiagnostics too early.
Dr. Fan: Yeah. So, I think in terms of seeing people for follow-up, at every step of the way, it's really important to ask yourself, am I sure about the diagnosis and am I sure about the treatment? If we are, and if the disease is progressing or responding the way that we expect it to, then that's great. Then our job as a neurologist is probably threefold. So one is to make sure that we get a really good quality exam to say, is this stable, better, or worse? Number two, is to look at the immunotherapy plan and say, well, one, is this going to be monophasic or chronic? So, do they need maintenance immunotherapy? And if they are on maintenance immunotherapy, do we need to change that in any way? So, have we been able to achieve pharmacologic remission? And then number three, is symptom management. So, a lot of these patients will have pretty significant pain, significant morbidity, disabilities that still need to be treated and supported even if their disease is in pharmacologic remission. And so that's important to address.
Dr. Monteith: What clinical pearls should we be thinking about when it comes to treatment?
Dr. Fan: For treatment, we'll take the example of vasculitic neuropathy. First and foremost, you want to make sure that the inflammation is still active and that it's not burned out. If it's active inflammation, then there are two main aspects that you want to think about. One is what does it take to address the active inflammation and make that stop? Unfortunately, a lot of our options for stopping active inflammation, for example, in vasculitic neuropathy, is corticosteroids, which comes with pretty significant side effect burden and not really a great option for long-term treatment. So, the second level that you want to think about, is this a disease that will require chronic maintenance immunotherapy? Is this monophasic or is this chronic? If it's going to be chronic and there's a risk of recurrence, then you want to start the patient on some sort of maintenance immunotherapy right away so that by the time you're tapering the corticosteroids, the maintenance immunotherapy has had time to kick in and take effect and take over. When you're prescribing and managing these immunomodulation transitions, it's very important for us to know how long does it take for the treatment to kick in, how long does it take to wear off, and once we know that, then that will guide how quickly can we taper corticosteroids and how quickly can we expect a steroid-sparing therapy to be able to take its place.
Dr. Monteith: And one thing you had also mentioned is the potential use of MRI or PET imaging for targeted therapy. Can you speak a little bit about that as well?
Dr. Fan: So, the use of these technologies like MR neurography and FDG-PET, they've existed for a long time, but this is an emerging role in inflammatory neuropathies, especially in diseases where inflammation can be very patchy and can be very hard to localize. So, having a modality in which we can really visually find areas of inflammation that's attacking the nerves can be very, very helpful in evaluating the state of disease and how they're affecting the nerves.
Dr. Monteith: Well, I think that sounds like a really exciting area.
Dr. Fan: Yes, I think so.
Dr. Monteith: Thank you very much for being on our podcast. I really enjoyed this conversation. I know I learned a lot as well as many of our listeners.
Dr. Fan: Thank you so much for having me. Pleasures all mine.
Dr. Monteith: Today, I've been 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. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to our listeners for joining today.
Dr. Monteith: This is Dr. Teshamae Monteith, Associate Editor of Continuum Audio. We hope you've enjoyed this subscriber-exclusive interview. You can get CME by completing the evaluation at continpub.com/audiocme. Thank you for listening.