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Neurologic complications of substance use may be the first symptoms that lead patients with substance use disorders to seek care. Neurologists have a key role in identifying patients with substance use disorders and connecting them to treatment.
In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Adeline L. Goss, MD, author of the article "Neurologic Complications of Drug and Alcohol Use" in the Continuum® February 2026 Neurology of Systemic Disease issue.
Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota.
Dr. Goss is a neurohospitalist and associate chief of neurology for Highland Hospital in Oakland, California.
Additional Resources
Read the article: Neurologic Complications of Drug and Alcohol Use
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More about the American Academy of Neurology: aan.com
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Host: @LyellJ
Full episode transcript available here
Dr Jones: A big part of neurology is solving mysteries. Patients can show up with all kinds of mysterious symptoms. Sometimes the diagnosis comes from within, some internal disruption of neurophysiology. But sometimes the problem is a complication of drug or alcohol use. Today we have the pleasure of speaking with Dr Adeline Goss, who recently authored an article for Continuum on this exact problem, a topic all neurologists need to be familiar with.
Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast.
Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today I'm interviewing Dr Adeline Goss, who recently authored an article on the neurologic complications of drug and alcohol use for our latest issue of Continuum on the neurology of systemic disease. Dr Goss is a neurohospitalist and the associate chief of neurology at Highland Hospital in Oakland, California. She's also an accomplished writer, broadcaster and podcaster. Dr Goss, welcome, and thank you for joining us today. Why don't you introduce yourself to our listeners?
Dr Goss: Great to speak with you, Dr Jones. Yes, I'm Adeline. I also go by Addie Goss.
Dr Jones: So, before we get into the discussion, we're going to start off today with something fairly new to the podcast, the Continuum Audio trivia question. So, we all know that alcohol and other substances have many potential complications in that use of these substances fluctuates over time. But this one stood out to me from your article, Dr Goss, just for the sheer size of the change. So, for our listeners, here's the question. Accidental exposures to what substance increased a whopping 1,375% between 2017 and 2021? I'll read that again. Accidental exposures to what substance increased 1,375% between 2017 and 2021? So, stick around to the end of our interview for the answer. And let's get right to it, Dr Goss. If you had a single most important message to our listeners from your article, what would it be?
Dr Goss: Well, I mean, many of us went into neurology because of the way that neurologic illnesses can be life-changing for patients. And I work as a neurohospitalist at a public hospital in Oakland, California. Many of my patients are admitted for neurologic conditions related to substance use. And when I see my patients later in the discharge clinic, many tell me that the last day that they used meth or the last day they used cocaine, the last day they smoked, was the day they had their stroke or whatever they came into the hospital for. I think the most important message is that hospitalization for a neurologic condition related to substance use can interrupt use patterns, can motivate change. And therefore, as neurologists, we really have an opportunity to connect to our patients and connect our patients to substance use treatment and make a dramatic difference in people's lives in this regard.
Dr Jones: I think that's a fantastic point. I enjoyed a point you made in your article---and I can't remember exactly how you phrased it, I won't say it as well---that you think of the syndromes through which alcohol and drug exposures can present. Those syndromes almost always could end up of other primary neurologic disorders. So, put a different way, when a patient presents with a neurologic problem, most of the time an exposure could be on the differential.  And so, we really do have a responsibility as neurologists to be familiar with these.
Dr Goss: To be familiar with these and to know how to connect patients to resources to try to get treatment.
Dr Jones: Totally agree. And you touched on the public health aspect of this. It's really hard to talk about drug or alcohol use without acknowledging the public health impact particularly of opioids, which has been a crisis for most of this century. Right? And I think most of our listeners will be familiar with the rapid rise in opioid-related deaths. But there might be a glimmer of optimism there. Is what I've seen true, that opioid-related deaths may have plateaued?
Dr Goss: So, yes, it's true that opioid-related deaths, overdose deaths in general, have begun to decline, actually, since 2023. And that's in part because overdose deaths really surged early on in the Covid-19 pandemic, in the setting of all of the social disruption, reduced access to services, and social isolation that occurred with the pandemic. But there were really multiple factors there. So, as you mentioned, there was this really rapid rise in illicitly manufactured fentanyl. Fentanyl became a major driver in overdose deaths starting in the mid-2010s. And by the late 2010s, it overtook heroin and prescription opioids as drivers of overdose deaths. And then this just collided with the pandemic in 2020, causing skyrocketing deaths. So, as we know as neurologists, fentanyl is more potent, it's shorter-acting, and it's also cheaper than heroin. It can cost as little as 50 cents or a dollar a pill. Thankfully, as services have rebooted and also as naloxone has become more widely distributed, there has begun to be a decline in opioid overdose-related deaths. So, we're relying on provisional data from the CDC for the most recent years, but that shows about a 24% decline in annual overdose deaths, comparing late 2023 to late 2024. And that's real. That comes out to 70 lives saved per day. Unfortunately, deaths still remain above prepandemic levels, and we're still talking about 87,000 drug overdoses per year. So, I would agree, a glimmer of hope. But we're still seeing overdose as the leading cause of death among young Americans aged 18 to 44. And there's a very long way to go.
Dr Jones: 23% is a big number, and that is certainly exciting to think about, but we're still above that long-term secular trend. So, hopefully whatever is happening to bring that down, hopefully it continues. And we talk a lot about- appropriately, we talk a lot about opioid exposures and some of the neurologic presentations of opioid use and toxicity, but alcohol use disorder is the most common substance use disorder, correct? I learned that from your article. And it has been for some time, and it has well-known acute and chronic toxicities. But I think many of us have been taught something of a myth in the acute treatment of patients who may have thiamin deficiency or Wernicke's encephalopathy. Can you tell us a little more about that?
Dr Goss: Yeah, sure. So, boy, what is my favorite vitamin? As a neurologist, I think thiamin is my favorite vitamin. Thiamin is a cofactor in- for several enzymes that are involved in glucose catabolism. And it's necessary to synthesize myelin and several neurotransmitters. And as we know, alcohol use disorder leads to reduced nutritional intake and impaired digestion and absorption of nutrients. And this can lead to deficiencies in water-soluble B vitamins, including thiamin, as well as trace elements. The thing about thiamin is that thiamin deficiency often appears first, because the body's stores of thiamin deplete in about 4 to 6 weeks. You know, we're traditionally taught if a patient presents with symptoms concerning for Wernicke's encephalopathy, that if they're also hypoglycemic or just in general, we have to get glucose into them first, because we don't want to tax these thiamin-dependent glucose catabolism pathways. But really, there's no reported case of a single glucose bolus precipitating some dramatic symptomatic thiamin deficiency. It's thought that harm would come potentially from prolonged carbohydrate administration without thiamin. And so, if a patient in front of you is both thiamin deficient and hypoglycemic, you just treat both. You treat both emergently. But it doesn't really matter in what order you do so.
Dr Jones: That's good to know that doing the right thing for the patient can involve using either of those in whatever order. And I agree with you, I don't think I've ever hurt anybody by giving them thiamin. It's an easy one to miss and an important one to remember in the right context. And speaking of, and I think a lot about in your article, Dr Goss, I can see a neurologist seeing a patient in the emergency department or in the hospital or even in the clinic thinking about the wonderful points in your article. But we know that when alcohol or substance use enters our mind on the differential, the next impulse is to test for it. And we also know there are pitfalls of drug screening, doing urine drug screens, etc. How do you approach testing when you think about a potential drug-related complication in their differential?
Dr Goss: So, like most people, I would start with a urine drug screen for any patient who's presenting with a possible toxidrome or some substance-related neurological presentation. These urine drug screens, they're rapid, they're inexpensive, they're immunoassays for traditional drugs and their metabolites. So, usually amphetamines, cocaine, opiates, plus/minus cannabis. But I think the first thing to note is that they miss entire categories of drugs, and not just drugs that are not in that list. They miss synthetic opioids, including fentanyl. One group is keeping track of this number. So, I have an update for mid-2025. And that's that 30% of U.S. ED overdose encounters as of mid-2025 included fentanyl testing. Only 30% for patients who are presenting with an overdose syndrome.
Dr Jones: And that's for one of the most widely used synthetic opioids. So that's really a striking number.
Dr Goss: Yeah, one of the most widely used and one with the greatest rate of complications. So, states can make a difference here. In 2022, California passed a law requiring fentanyl testing on hospital urine drug screens and several states have followed. And so that number is rising, the rate of testing for fentanyl. But that's just a really key thing to know, that that one is often missed. Other just important pitfalls, the timing of the urine drug screen matters because for most substances, it only picks up the drug within 24 to 72 hours after the last use. With amphetamines and cocaine going out a couple more days after that, especially in patients who use repeatedly. And then also, notably, there's a risk of false positives. This is especially true with amphetamine use, and beta blockers are one of the drugs that can lead to false positives on an amphetamine test, on a urine drug screen. So, I'll share that I've had several patients who have presented with intracerebral hemorrhage and who tested positive on the emergency department's urine drug screen and who adamantly stated that they do not use amphetamines, they've never used amphetamines, and they didn't ingest anything that could have contained amphetamines. And when we did serum confirmatory testing, in fact, their amphetamine testing was negative, and all those patients had received esmelol or the labetalol in the ED to treat their blood pressure related to their ICH. So false positives can occur with, you know, other medications like decongestants and certain antidepressants. But beta blockers are a key one to know. And then finally, there are just a number of things outside of that short list of substances that I mentioned, including a huge range of novel psychoactive substances that would not be tested for on a standard urine drug screen. And for those, you'd require serum testing, or at some large academic centers or specialty toxicology labs, you can actually do liquid chromatography high-resolution mass spectrometry, with- which is basically unbiased testing for any substance that's present in the patient sample. So, I guess, you know, you asked about my approach. Start with the urine drug screen, but there's no substitute for good history-taking and close examination of your patient's general examination, not just their neurologic presentation. And if patients are presenting with a toxidrome that I would expect would show up on a urine drug screen but it's negative, there are other confirmatory tests that can be sent, although they're often send-out labs and come back in a very delayed fashion.
Dr Jones: So, in other words, it's complicated, which usually means it's humbling. And if I'm understanding it correctly, there's the risk of the false positive on the urine drug screen. And then there's the risk of the false negative if we think we're screening for something that might not even be on that initial screen. So, that's a wonderful reminder that these are clinical diagnoses and we have to keep our clinician hats on while we're thinking about how to establish these diagnoses or exclude them. So, back to opioids, Dr Gross. There are some really peculiar neurologic syndromes associated with opioid overdose. Tell us a little about those.
Dr Goss: Well, I mean, some of these were described first with heroin. So, we can start with the one that almost anybody has heard of, heroin-associated spongiform leukoencephalopathy, which we know is associated with a practice known as "chasing the dragon," which is inhaling vapors of heroin heated on foil. But we know now that this syndrome can occur with other opioids, including fentanyl. The clinical features are, you know, apathy, cerebellar signs, quadriparesis, parkinsonism, myoclonus, and some patients progress to coma or even death. But on MRI you're seeing, you know, these confluence symmetric white matter diffusion restriction and T2 hyperintensities in the cerebellar white matter and the posterior limb of the internal capsule that spare the subcortical U-fibers. So, you know, I think this is kind of the classic example of something that's symmetric, that has a very obvious and interesting MRI pattern. But as time is passing, we're seeing more and more similar types of syndromes of leukoencephalopathies, but with different clinical presentations and MRI characteristics. So, another of these is CHANTER syndrome. This is an opioid overdose-related presentation where people have stupor and coma. And on the MRI there, you see bilateral symmetric diffusion restriction in the cerebellar cortex, in the hippocampi, in the basal ganglia. And it spares the cerebral cortex. And notably in these cases, patients can progress to cerebellar edema, to obstructive hydrocephalus. And some require suboccipital craniotomy. I had a week recently at Highland Hospital, where I work, where we had two of these cases in the same week, in just a community hospital. And there's a similar syndrome in children known as POUNCE syndrome with profound cerebellar edema, and many patients require posterior decompression. So that's another different distribution of findings with a different outcome. Fortunately, there's a milder sort of phenotype of opioid-associated amnestic syndrome, is what it's been described, where there's primarily DWI changes in the hippocampi and the globus pallidus. So, patients primarily present with an amnestic syndrome, mostly anterograde amnesia. Seeing these in practice, I'm not sure that patients always fall into one bucket or another. But in general, you'll see some degree of symmetric diffusion restriction or symmetric white matter changes that clearly point to a toxic presentation, a toxic syndrome, as opposed to pure anoxia, for example. And it's important to know that because from a prognostic standpoint, anoxic brain injury, which can occur after cardiac arrest and after opioid overdose, can look different than some of these syndromes. Finally, heroin has been associated with myelopathy, but also that's been reported on with fentanyl. So, I think some of these conditions got their reputation from heroin. But as fentanyl has proliferated---and prior to that as prescription opioid, you know, misuse had proliferated---we're seeing similar syndromes with all of the opiates.
Dr Jones: And I think it's a good case in point that you can have multifocal disease and it be a manifestation of an intoxication, and I think that's a really good reminder that we have to have many of these syndromes in our differential, we have to be aware of them, otherwise we might miss them or attribute them to another mechanism. Dr Goss, our last issue of Continuum that was dedicated to the neurology of systemic disease came out in 2023, and here we are in 2026 publishing our latest issue, including your article and this podcast. Since 2023, have there been any emerging patterns or novel agents of abuse or misuse out there?
Dr Goss: The short answer is yes, and I would say the reason is just the supply is moving at more and more rapid speed. The relationship between the internet and drug supply has really informed what's out there at any given moment. So, the turnover in the market can change in weeks, not in years. And there's all of this distribution through social media and encrypted apps. And then manufacturers are kind of continuously tweaking chemical structures to evade law enforcement. In the process of researching this article, I came across some, I mean, really wild examples. To be clear, these are not- not all these are common substances, but I think the general phenomenon should be known that people can walk into a vape shop or walk into a gas station or meander around online and buy some really weird stuff. So, in 2024, there was this nationwide recall of a product called Diamond Shrooms that was sold online and in smoke and vape shops, and this was billed as, like, a hemp and mushroom mixture. But it led to multiple- I mean, over 100 cases of seizures and agitation and depressed consciousness and a few possible deaths. And when the contents were analyzed, they included psilocybin analogs and pregabalin. I mean, some weird stuff. And so, those have been pulled. But people are constantly inventing and marketing these different substances. I think another example… we all know about nitrous oxide and its association with B12 myopathy. But the use of nitrous oxide has really changed. Companies are selling large canisters online and in vape shops, and they're flavored, like, in blue raspberry flavor. And unfortunately, there's been a rise of nitrous among youth. So, we're seeing not just increased cases of myelopathy, but also a 2025 study in JAMA found a spike in deaths attributed to actual nitrous oxide overdose. And so nitrous, I think, had not been that commonly used a few years ago, but has become more common in the last couple of years.
A final one I'll just mention is ketamine. So, ketamine has certainly appeared in reviews of neurological syndromes related to substance use for a long time, and it's also been studied and used off-label for mood disorders in outpatient infusion clinics for some time. But in the pandemic, there was an expansion in telemedicine, as we know, and an associated proliferation of teleclinics that were prescribing very frequent, even daily oral and lozenge and nasal formulations of ketamine, which has led to increased rates of misuse. So, you know, acutely, the syndrome associated with ketamine intoxication is very brief. And often by the time people come to the emergency department, their symptoms have already worn off. But long-term, frequent use of ketamine is really still being studied. There seems to be an association with persistent neuropsychiatric effects like cognitive impairment, psychosis, persistent depressive symptoms. And so, you know, I think it's just important to realize that while the list of substances may look pretty similar to 2023, the use patterns, the distribution patterns are continuing to change. It's hard to keep up. And while alcohol and opioids and stimulants are by far the most common substances that a neurologist is going to encounter in daily practice, there's this ever-expanding range of possible substances that can trigger neurologic syndromes, both acute and chronic.
Dr Jones: And I think that might be the best possible plug to read your article, because it is evolving and we have to stay on top of it. And we really can't be complacent with it. So, thank you for that update. Okay, back to our trivia question. Accidental exposures to what substance increased a whopping 1,375% between 2017 and 2021? Dr Goss, what do you think?
Dr Goss: That was THC-infused edibles. Specifically, these would be THC-infused substances that are often marketed as looking like candy or snacks or cereal. Exactly what a kid might want to get their hands on. And unfortunately, accidental cannabis exposures in children under age five went up by 1,375% between 2017 and 2021, and 600 of those patients required critical care admission.
Dr Jones: Yeah. So, just a mind-blowing number, and obviously something for us to be on the lookout for, especially if you see children in your practice and someone comes in with CNS depression or stupor, it's one to not miss. So that was something I learned in reading your article, among many other things. And Dr Goss, I want to thank you for joining us. I want to thank you for such a great discussion. I learned a lot from reading your article, I learned a lot just from our conversation today, and I suspect our readers and our listeners will too.
Dr Goss: What a pleasure. Thank you so much, Dr Jones.
Dr Jones: Again, we've been speaking with Dr Adeline Gross, author of a fantastic article on neurologic complications of drug and alcohol use in our latest issue of Continuum on the neurology of systemic disease. Please check it out, and thank you to our listeners for joining us today.
Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use 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.

Neurologic care during pregnancy and menopause requires careful attention to the dynamic interplay between hormonal transitions, evolving evidence on diagnostic and treatment safety, and the lifelong risks associated with neurologic complications of pregnancy.
In this episode, Katie Grouse, MD, FAAN, speaks with Sara C. LaHue, MD, author of the article "Neurologic Complications of Pregnancy and Menopause" in the Continuum® February 2026 Neurology of Systemic Disease issue.
Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California, San Francisco in San Francisco, California.
Dr. LaHue is an assistant professor of neurology for the Weill Institute for Neurosciences in the Department of Neurology at the University of California, San Francisco School of Medicine in San Francisco, California
Additional Resources
Read the article: Neurologic Complications of Pregnancy and Menopause
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
Full episode transcript available here
Dr Grouse: Despite the high prevalence of neurologic conditions in women, critical gaps remain in training, research, and clinical guidelines on sex and gender specific considerations across the lifespan. Today, I have the opportunity to speak with an expert on neurologic complications of pregnancy and menopause and coauthor of the and women's neurology curriculum core competencies, Dr Sara LaHue about the latest issue of Continuum on neurology of systemic disease.
Dr Jones: This is Dr Jones, editor in chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast.
Dr Grouse: This is Dr Katie Grouse. Today I'm interviewing Dr Sara LaHue about her article, Neurologic Complications of Pregnancy and Menopause, which appears in the February 2026 Continuum issue on Neurology of Systemic Disease. Welcome to the podcast and please tell us more about yourself.
Dr LaHue: Well, thanks so much for having me. I'm really excited to talk about this topic. So, I'm Sara LaHue. I'm a neurologist at UCSF, assistant professor of neurology, and a neurohospitalist. So much of my role is taking care of people who are coming into the hospital with urgent and emergent neurologic conditions. And so that's very much a framing that I come to this chapter with.
Dr Grouse: I just want to start by congratulating you on your article, which is such a phenomenal compendium of important neurologic issues related to pregnancy and menopause, which I think I really needed and a lot of us really need and was missing, I think, in all of the literature out there. This article will be such an important clinical resource. I know for me, and I'm sure for many of our listeners, this may be a difficult question to answer because of how comprehensive the article is. But what do you hope will be the main takeaway for those who read your article?
Dr LaHue: So, I really hope that listeners walk away with understanding that pregnancy and menopause are not contraindications to providing excellent neurologic care. I think too often we default to withholding treatment, pseudo-assumed risk, rather than actual evidence of harm. And so, I think that the key message here is that protecting maternal health is protecting fetal health, and that under-treating neurologic conditions during pregnancy can harm both mother and baby.
Dr Grouse: You did say specifically in your article that I thought it was so important that presumption of harm from medications during pregnancy, due to lack of evidence rather than evidence of harm, was something that we really had to be aware of, of that bias. And how do you recommend neurologists listening to this podcast approach situations where diagnostic or management strategies become less certain due to safety considerations in pregnancy?
Dr LaHue: Yeah, that's such an important question. I really frame it as a risk-benefit calculation with a patient, and I'm very transparent about what we know and what we don't know. And I emphasize that untreated disease may also impact fetal health. I use resources like LactMed and pregnancy registries that can help provide some of the more latest data. And then when evidence is limited, I document our discussion thoroughly, and I'll often involve maternal-fetal medicine colleagues for their multidisciplinary input. So, the goal is really to have an informed, shared decision-making process rather than a reflexive avoidance of all treatments.
Dr Grouse: I think that's really important to reiterate, and I think something that we're all I think working on as we try to manage these difficult situations and conditions. Now, I want to switch gears a little bit and ask. Your article was so comprehensive and so helpful, but what isn't in the article that you wanted to put in?
Dr LaHue: There was a fair amount that I ended up having to take out. So, this is a question that's near and dear to my heart. So, I would have liked to include more on the neurodevelopmental outcomes for children who are exposed to various neurologic medications in utero. And I also wanted to discuss more about transgender and non-binary individuals who are experiencing pregnancy and menopause, as they're often underrepresented in research. They've faced unique challenges accessing care.
Dr Grouse: Now, I was really struck by one statistic in your article, specifically that intimate partner violence is a leading cause of head injury during pregnancy, and that actually homicide is a leading cause of death during pregnancy in the postpartum period in the US, which was absolutely a surprising statistic to me. What does this mean for our listeners caring for pregnant patients with concussions and head injuries? What should we be doing differently?
Dr LaHue: This is also something that really struck me when I first encountered it. I think that the statistics should really fundamentally change how we approach head injuries in pregnant patients. I think we need to screen everyone routinely and privately for violence in the home and in the relationships, and to document injuries very carefully. But we also need to be prepared if someone does screen positive. And so, it's important to be familiar with what's available in terms of resources within your community, where you work, and also to remember that that strangulation in particular is something that can cause dissection and stroke. And so, to maintain a high index of suspicion for any kind of vascular injury in these cases. So not just thinking about head injury itself, but also thinking about complications of strangulation as well.
Dr Grouse: Really a great reminder of the role that we can play in our own careers and our own clinical settings when we see cases like this. So, I really appreciate that this point was made, and I hope this will change people's practice. Now switching gears to stroke in pregnancy. Could you walk us through your evaluation and management of a patient who comes in with acute stroke in the peripartum period?
Dr LaHue: This is such an important topic, and I think the first thing I'd like to emphasize is that time is brain. Whether or not you're pregnant. It's important to get whatever imaging modality is going to be fastest. Get the CT or get the MRI as soon as you can. Don't delay for fetal concerns. The radiation risk is minimal compared to missing a treatable, disabling stroke. In terms of treatment, thrombolysis and mechanical thrombectomy should be considered just as in a non-pregnant person, when the benefits outweigh the risks. And so, I think the key is involving obstetrics early for shared decision making, and being very transparent with what treatment options are available for the individual, and to not let pregnancy alone stop you from offering standard stroke therapies.
Dr Grouse: Definitely a helpful resource, and I think the resources that you put in specifically around the considerations and differentials in these various populations. Postpartum, while still pregnant during the period of period, I think is all just so helpful and a great review. So, I encourage our listeners to check that out. Now switching over to the topic of menopause. I have to say, I really appreciated your coverage of neurologic issues related to the perimenopause period. What do you think is the biggest debate or controversy in this area?
Dr LaHue: I think this has to be our understanding of the use of menopausal hormone therapy. The pendulum, when using menopausal hormone therapy, has really swung dramatically. So, we went from routine use to predominantly avoidance. After the Women's Health Initiative was published in 2002, and now we're finding that we're starting to come more to a middle ground. I think there's still great debate when it comes around timing of initiation, formulation of the different therapies, a route of administration and also the dosing, as well as just including how to individualize therapy for individuals with neurologic conditions.
Dr Grouse: Well, going into that a little further, I know I get a lot of questions about the use of hormone therapy as it relates to stroke risk and particularly in higher risk patients such as patients who've had prior strokes, dissections, a history of migraine with aura. And I find it hard to get the answers in the literature that's out there. How are you counseling these patients?
Dr LaHue: So, I think this is where discussions around the route of administration and dosing become especially important. And this is where there's emerging literature that I think is helping to guide some of these discussions. So, for higher risk patients, I discuss how low dose transdermal formulations which can bypass hepatic metabolism and reduce clotting risk. These are medications that can appear safer in those higher risk individuals. I think the key is really individualizing the risk-benefit discussion with the patient. For a woman with severe vasomotor symptoms that are affecting sleep and cognition, who had a remote stroke. I think this is a person for whom low dose transdermal patch might be a reasonable option. All of these factors end up being considerations for that shared decision-making.
Dr Grouse: Now your article covers another topic that I often get questions about, and that's specifically regarding safety of vaginal delivery for patients with neurologic conditions that are sensitive to increased intracranial pressure. Could you summarize your advice for these types of questions when they come up?
Dr LaHue: So broadly speaking, most neurologic conditions don't require C-section delivery. And this is a procedure that, just globally speaking, as has been increasing dramatically. And so, I think that's the key message that really, most neurologic conditions don't require a C-section as a main indication. And really, the indication should be based on obstetric considerations. For most conditions, like controlled idiopathic intracranial hypertension, a vaginal delivery is fine. But for patients with mass effect or obstruction at the foramen magnum, a C-section with general anesthesia, it's probably going to be safer. The transient increase in intracerebral pressure that can come with pushing. It hasn't really been shown to harm patients who have stable, treated neurologic conditions.
Dr Grouse: I really appreciated the advice that you given in the article, which was that if generally you feel like this would be a patient who would be safe to get a lumbar puncture, you have a little less concern about vaginal delivery versus those that you feel would not be safe to get a lumbar puncture, that you'd be more leaning towards a C-section.
Dr LaHue: Yeah, that's exactly right.
Dr Grouse: Now, why do you think we have so many gaps in our understanding of how pregnancy and menopause affect neurologic conditions?
Dr LaHue: So, I think it really comes down to a perfect storm of factors. So, in 1977, the USFDA came down with the recommendation, stating that it was best to exclude all women of reproductive potential from both phase one and phase two studies. And this recommendation wasn't reversed until 1993. And there are also concerns around liability and also the fact that pregnancy is a temporary state is something that may falsely minimize the potential for delays. The potential for harms that come with delays in treatment. And I think that the fact of menopause is also historically been dismissed, despite this is something that is affecting half of the population. I think we need systemic change. We need to mandate inclusion in research. We need funding for dedicated studies. We also need to recognize women's health as a core competency and not just a special interest.
Dr Grouse: That all sounds like a great roadmap for improving our knowledge. And I really hope we get there. But hearing you talk about it really does give me hope that we can improve how we are understanding and treating these conditions. Now, your article included a really helpful overview of headaches in pregnancy, and that's certainly something I think many of our listeners are very familiar with. We do have a lot of questions around that, and I think there's a lot of areas where we don't really always know what the best thing to do is. I think that your article really gave a lot of great information and a really great framework to think about. It would be wonderful to hear you walk through your approach to evaluation of a patient who was pregnant with a new onset headache.
Dr LaHue: You'll see in this chapter that I introduce a mnemonic that's spelled out pericardium as a framework for thinking about headache and pregnancy. And here are the you specifically points to an unusual headache, referring to a new or atypical presentation of headache for the patient. I think this is an important place to start, because one of the initial considerations should be this is a new headache, or is this an old headache? If this is a patient who already has a preexisting diagnosis of migraine or some other primary headache disorder, then it's certainly possible that the headache that they're experiencing during pregnancy is also a continuation of their primary headache disorder. But certainly, our role is to make sure that we're not missing a scary complication, a secondary headache that could be dangerous to the patient. And so, then this is where I also think about, well, where are they in the course of their pregnancy. Is this person currently pregnant or are we in the postpartum period? When someone is after 20 weeks gestation, one of the first things to consider is going to be preeclampsia. And so, it's important in those individuals to check blood pressure, check urine to rule out preeclampsia, as this is always going to be top of mind after 20 weeks.
I think it's also important to emphasize that preeclampsia is not just a condition that can occur when someone is pregnant. This is also something that can occur postpartum. One needs to be vigilant for looking out for this complication during both time periods. And then I think for new headaches, I really want to focus on what the timing is and any other red flags. For example, if it's a thunderclap headache and onset, then I might be worried about something like RCBS or cerebral venous sinus thrombosis. If the headache itself is orthostatic and patient may have had an epidural, then I might think about a post-dural puncture headache, which is a, unfortunately very common complication and reason for headache in the postpartum period. I think the key is that most dangerous headaches often will occur late in the third trimester or early postpartum. And I think it's also important to remember that if you need imaging to make the diagnosis, and you should get it. The risks of missing something serious far outweigh concerns that one might have around imaging. And when possible, it's certainly preferred to get an MRI if that's available.
Dr Grouse: I really did appreciate articles, overview of the various imaging modalities out there and the overview of risk versus benefits and times where they may or may not be needed. So, yet another very useful piece of information that I think that our listeners will appreciate in your article. Now, I'm curious how did you get interested in this area of neurology?
Dr LaHue: So, it really was my interest in both reproductive health and neurology that led me to go to medical school in the first place. I knew early on at the beginning of medical school that I was interested in neurology, but I also was very drawn to obstetrics, and I recognized in medical school and then further on as, as a resident, just how vast the knowledge gaps were. When I was counseling my own patients and I found this to be just a very frequent source of frustration as both a clinician and a researcher, I very much feel an obligation to try to help fill these gaps. And I've also just been very encouraged by an outstanding community of other neurologists that I've been able to meet in this space. It's been a just a wonderful collaborative network that we've been able to grow, both within United States and even more globally, when it comes to other neurologists who are interested in this topic. And I'm just very excited to see the direction that this field is going in.
Dr Grouse: Well, we can't wait to learn more as this field develops and more is understood about the right way to approach these types of diagnostics and treatments. So, thank you for all your work in this space. And it's been absolutely fascinating reading your article and talking with you today.
Dr LaHue: Well, thank you so much for having me, and I'm just so thrilled that these important topics are going to be part of this issue of Continuum.
Dr Grouse: Again, today, I've been interviewing Dr Sara LaHue about her article and Neurologic Complications of Pregnancy and Menopause, which appears in the February 2026 Continuum issue on Neurology of systemic disease. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to our listeners for joining today.
Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the Journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe AA and members. You can get to me for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

Prompt recognition of direct and indirect neurologic complications of systemic cancers and their evolving treatments is essential. Neurologists should be familiar with common and rare neurologic toxicities of conventional chemotherapy, immune checkpoint inhibitors, and CAR T-cell therapy.
In this episode, Teshamae Monteith, MD, FAAN, speaks with Amy A. Pruitt, MD, FAAN, author of the article "Neurologic Complications of Cancer and Its Treatment" in the Continuum® February 2026 Neurology of Systemic Disease 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. Pruitt is the William N. Kelley Professor of Neurology, Vice Chair for Education, and Division Chief in the Department of General Neurology for the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, Pennsylvania.
Additional Resources
Read the article: Neurologic Complications of Cancer and Its Treatment
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: As neurologists, we have a critical role in diagnosing neurologic complications of cancer from metastatic disease, seizures to neuropathies. Increasingly, the rapid development of novel treatments themselves, like immunotherapies, Car-T cells, and targeted drugs are causing new neurologic side effects, which we need to recognize, manage and anticipate as therapeutic developments evolve.
Dr Jones: This is Dr Jones, editor in chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast.
Dr Monteith: Hi, this is Dr Teshamae Monteith. Today I'm interviewing Dr Amy Pruitt about her article on neurologic complications of cancer and its treatment, which appears in the February 2026 issue on neurology of systemic disease. Welcome to our podcast. How are you?
Dr Pruitt: Thanks for having me.
Dr Monteith: Absolutely. Why don't you introduce yourself?
Dr Pruitt: As you said, my name is Dr Amy Pruitt. I'm a professor of neurology at the University of Pennsylvania, where I am also the clerkship director and have been for a long time. I'm the division chief of general neurology and the vice chair for education in my department.
Dr Monteith: You have a lot of hats.
Dr Pruitt: I do.
Dr Monteith: Okay. So, before we dive into all this great work that you did in the article, why don't you just let us know just a little bit about what led you to this career path?
Dr Pruitt: Sure. So, I've always been interested in the intersection between internal medicine and neurology; in fact had I've not been a neurologist. I probably would have been either an oncologist or infectious disease specialist. And that leads to doing neuro oncology and seeing a fair amount of CNS infections. I see both inpatients and outpatients and really enjoy my neuro hospitalist time because, honestly, as all of you who do consults on inpatient services know, there is an incredibly changing landscape of consequences of cancer therapies. And if you haven't been on service for a while, you probably don't even know the name, is much less the adverse effects of these medicines.
Dr Monteith: Okay, so you were just like me to write this article.
Dr Pruitt: Well, I think where it is directed, I think, as I said, that people who are seeing a lot of inpatients and who may not know it's a new consequences of cytotoxic or immunotherapies or T cell therapies and the different appearances and really prognoses, which have changed dramatically in the last few years in the field of systemic cancer.
Dr Monteith: Any other essential points of your article?
Dr Pruitt: So, I think there are certain areas where neurologists are going to intersect with oncologic patients even before oncologists do so, what tumors might present synchronously in the brain and the rest of the body. And those would include things like small cell and non-small cell lung cancer and melanoma, to a lesser extent, women who are surviving much longer now with good therapies for various versions of breast cancers, have one of the solid tumors most likely to present at first relapse in the brain, either in the brain metastases category or in the leptomeninges. So, these are the areas where I think it most likely that our neurologists are going to intersect with oncology. And then there is the burgeoning, thankfully, realm of long-term survivors who have had cancer therapies in young adult lives, sometimes in childhood. And we need to be abreast of the ever-changing spectrum of complications that will plague these people all their lives. And we can do a great deal to improve the quality of survival in these patients.
Dr Monteith: And of course, there has been a lot of great development in cancer research, which has led to novel therapeutics. So, can you tell us about a few of these therapeutics and their complications that neurologists need to know about?
Dr Pruitt: Sure. Well, as I said, some of the cancers you're most likely to encounter are lung cancer and melanoma. And here the prognosis has changed dramatically. A few years ago, someone with metastatic melanoma might have had a couple months prognosis. And now we're talking honestly about long term survivors, complete responses in lung cancer and melanoma, and really good responses in the breast cancer realm as well. So, these are dramatic changes. And these are ways neurologists need to know what the actual nuanced and much more variable prognosis is among patients with brain metastases. In order to give the patients good advice and also to give the radiation oncologist and the oncologist, the medical oncologist, good advice. So, for example, just in the realm of brain metastases, a stage change has been that people with asymptomatic metastases for, let's say, non-small cell lung cancer or melanoma might have systemic therapy rather than local therapy, local therapy being gamma knife radiation or less likely, whole brain radiation therapy, but really systemic therapy with responses and the brands that are nearly as good as those in the rest of the body. And sustained, durable responses. The article goes into great detail about what's available in the way of therapies for these cancers, like breast, HER2-positive breast cancer, like EGFR‑positive lung cancer and melanoma of various types. It's really quite amazing actually, to have anybody quote a seven-year survival of little over 40% in people who presented with non-symptomatic melanoma metastases. Unheard of, really. So, I think if you're still practicing, quote unquote old school neuro-oncology, you need to get up to date because you're giving patients and their caregivers good advice that will lead them to the very important therapies. You mentioned some of the immunotherapies. If we have time, I'm happy to go into those because those are really important for neurologic consultants in the hospital.
Dr Monteith: Yeah. Let's talk about immune checkpoint inhibitors. What do we need to know about them and their complications?
Dr Pruitt: So, they have a novel set of central nervous system and peripheral nervous system complications. These include both acute and subacute presentations. They can arise after the very first dose and usually do so within the first several doses. Importantly, even though the patient may be quite sick, about three quarters will recover entirely. However, the most common ones are actually the peripheral nervous system, and they have the highest morbidity and mortality rate. So, a very unfortunate combination of myasthenia, myocarditis and skeletal myositis has a high mortality rate and is very hard to treat in a group of people who have received these immune checkpoint inhibitors in the central nervous system, there can be cerebellitis, encephalitis. These again can be acute or subacute presentations. And the big discussion with the attending oncologist is, can we continue these therapies after we've withdrawn them, and for instance, treated them with steroids? Because you can imagine that if you knock down the immune system with steroids, you might make the patient temporarily better. But in so doing, you're negating the important consequences of the mechanisms of immune checkpoint inhibitors.
So, I would say probably in a given week on the inpatient service, I'll see five or so. So nearly a daily event when I see some major complication of immune checkpoint inhibitors. And again, I've already mentioned the histology in which those have been useful, but they're not indicated for a variety of other malignancies as well. And the Car-T cell therapies are a whole different set of side effects. And some of your listeners may know about cytokine release syndrome, which is nearly universal right after the infusion of the car T cells. But a few days later is where we come into action with the immune effector cell-associated neurotoxicity syndrome. Or ICANS can say that I'll refer to it as ICANS since then. These include focal neurologic symptoms and the form of what's often a conduction sort of aphasia, a predictable deterioration, and handwriting along with confusion. As far as the radiology of that syndrome, that's really pretty odd. It can range from a dramatic cerebellitis, just a dramatic basal ganglia syndrome, a dramatic and enhancing leptomeningeal syndrome to an absolutely normal MRI scan. And the important thing for our consultant consultants to remember is that the patient can look really, really ill, and you can turn to the team and say, you know what, there's a very good chance that it's going to get all better. So, supporting people through what are very good diagnostic and therapeutic algorithms that exist in the literature and are quoted in the Continuum chapter to help know when you should be giving steroids, when you should be giving tocilizumab, etc. these are tried and true therapies now, and the Car-T world has improved not only the prognosis of patients. And I remember seeing some of the very first Car-T patients, and we really didn't know what to do to help them, how to turn off the cascade of this immunologic reaction. Now we know how to do that. And it's important to stay up to date on those algorithms because you can make a big difference for these patients.
Dr Monteith: Yeah. So, this is great. We're going to dive back into the diagnostics, which is really related to my follow up question. I think you gave a really great pearl. And it's always can we keep going? Do we stop? So, I want to like dive into that question. And I assume that there are categories. Yes. You can, somewhere in between, and absolutely not. And so, tell me a little bit more about that thinking.
Dr Pruitt: Well that's a very nuanced question. And so, the answer that some oncologists will give you as well, they've had such a dramatic response. So maybe we don't need it anymore. It's never the neurologist's decision. It's always the joint decision with the oncologist. So, for instance, with a Merkel cell cancer patient develops a severe anti‑AChR syndrome on an immune checkpoint inhibitor. And we tell the oncologist maybe you shouldn't go back and do that again. And the person says, never mind, he'll be fine. He's already had the response that we want, but that's a difficult question to answer because, for instance, in a slightly different subset, let's look at multiple myeloma patients. And I spent a fair amount of time on multiple myeloma in the article because it affects the nervous system in so many ways. And we have so many different therapies for these patients, one of which is a Car T-cell. And this is a B-cell maturation antigen, Car-T. It's different from the ones that we know for lymphoma and leukemia. And it has a different set of neurologic problems, which unfortunately do preclude going back to taking a Car-T cell therapy again. And just to make a long story short, this particular complication makes the patient look Parkinsonian.
The consult you're probably going to get from the medical services is patients weak. Well, the patient is not exactly weak. He is Parkinsonian. He has a extrapyramidal rigidity, sometimes a tremor a negative cat scan and a B-cell maturation antigen syndrome occurs not at the sort of 5 to 7 day mark about ICANS that we just discussed, but rather a month or so out and a month or so out. It's not when you're expecting to see Car-T cell therapies. So, patients end up getting worked up extensively for, let's say, some sort of infection, when in fact, what we should be looking at is a newly described complication of Car-T cell therapy. So, the part of my article on multiple myeloma is one that's really important because as you know, it's such a common hematologic problem among older people. And many of these people may have direct complications of multiple myeloma, such as direct tumor infiltration of nerves. POEMS syndrome. So, it's really a wealth of neurological issues for us to contend with for these people.
Dr Monteith: Yeah. And I know you've really done a great job of adding lots of wonderful charts, including understanding the time course of some of these complications, when to anticipate, because I think some of it is about when to anticipate some of these complications.
Dr Pruitt: Well, exactly. Yes. Given the time constraints, I've made a lot of tables because there was a lot of information. And those, I think, are the kinds of things that a consultant should know: what should I be thinking about at this point in time? And that sort of leads us to what are the later complications of these things. And those include many medical things, from failure due to neoplasia, morbidity, radiation, chemotherapy agents, the long-term and medium-term consequences of these things for people. Are going to come back to our office as well. Immunocompromised patients, such as the ones and heavily treated patients that I just mentioned, may lack a robust inflammatory response. And they can have infections really at any time out. Some are predictable, as in our leukemia patients who have had hematopoietic cell transplant. So, we kind of know when to expect viral infections, nosocomial infections, progressive multifocal leukoencephalopathy, many other things down the road. But in this era of COVID, we know that these patients are more susceptible to the dire effects of COVID, and they may not mount a good vaccination response. We have seen types of neurologic complications of all sorts of infections, including babesiosis this year, and persistent enteric viral meningitis. So, the patient can present a very atypical fashion. And the neurologic consultant has to keep a really open mind about the broad differential of what might be happening.
Dr Monteith: And you do have a section under imaging and metastatic disease. Are there any like new sequences or a way to kind of tease out complexities?
Dr Pruitt: So, there is marked variability in the radiographic appearance of brain metastases. And I must confess that I made a very large collage of all the different representative types of things. And I think that's important for neurologic consultants to recognize that some metastases don't enhance. They don't all look like ring-enhancing lesions. Some can be much more diffuse, particularly if the patient has received something like a VEGF inhibitor like bevacizumab therapy can look exceedingly different. They can involve the dura, which should be treated differently. There can be simultaneous leptomeningeal and disease. So as far as I know, sequences perhaps not so much. Although if one is thinking about the differential between radiation-related injury and someone who's already been treated versus tumor recurrence, then we have some pretty good microscopic data, some susceptibility weighted images, other ways of getting whether this is really radiation related change or tumor recurrence, a major problem obviously.
What we also know about radiation is kind of a theme of the article is use it as infrequently as possible, because we just talked about some of the other therapies that we have. We may need to give local therapy for symptomatic patients, but we give as little as possible, and we try never to give whole brain radiation therapy. I'll go on record as saying that it's certainly necessary. Sometimes people have diffuse lymphoma, this disease that's recurred, they have multiple metastases in a sort of miliary fashion may be necessary, but if you can use gamma knife radiation, if you cause any use form of focal radiation, new in the leptomeningeal world is proton therapy for spinal metastases. So quick sparing techniques. And this is something that should always be considered when you're consulting on someone in a place in which you have the option of proton therapy. So, I would say that distinguishing between radiation necrosis and recurrent tumor and the use of protons are the big news in the radiation therapy world. And don't give whole brain radiation therapy if you can avoid it.
Dr Monteith: Yeah. I'm getting a flashback from residency because, you know, that always happens. And the radiologist saying, you know, we need more information when you put in those orders. And so, I think with this whole era of new chemotherapeutic agents and how they could present on imaging and give the radiologists as much information, including the type of chemotherapeutic agent used.
Dr Pruitt: Yeah, I think particularly in the transplant world. So, the leukemia lymphoma patients who have received one of the calcineurin inhibitors, like tacrolimus or cyclosporine, that induces a whole set of complications, some of which are visible radiographically. There's a delayed leukoencephalopathy. There can be stroke. There can be SMART syndrome, stroke like migraine after radiation therapy. And perhaps many of our listeners have been confronted with someone who has a prolonged focal deficit, say, a hemianopia and maybe a hemisensory deficit with or without a subsequent headache. It goes on for days to hours. It looks peculiar on the MRI scan because it's not then a vascular distribution. There's sort of diffuse gyral swelling, flattening of the EEG on that side, the patients getting steroids and valproate and anticoagulation and angiography and all. It doesn't need any of that. The syndrome of stroke, like migraine after radiation therapy, needs to be recognized. And best thing to do is don't just do something. Stand there. You should wait until it goes away. And so, I think that's we are seeing this increasingly, that we first reported this in young adults who had been treated years ago for medulloblastoma. So, it was posterior fossa tumors primarily. But this has now been broadened, as you know, to include supratentorial tumors of many types and adults at various times out from their radiation therapy from a few months to many years.
Dr Monteith: I should ask you in writing this article, clearly you have a wealth of knowledge, but in kind of just putting this together, what surprised you?
Dr Pruitt: I think what surprised me is the increasing range of complications and that virtually anything needs to be thought of central nervous system or peripheral nervous system. With some of these newer therapies. There is a chart in there about the conventional cytotoxic therapies, and we're all familiar with things like methotrexate and that sort of thing. But what surprised me really is the increasing diversity of complications of these newer drugs, and also the fact that I didn't know some of the third and fourth generations of the tyrosine kinase inhibitors too. When you look at even the year of 2020, neurologic drugs were second only to oncologic drugs and FDA approval even at the height of COVID. So, don't feel badly if you don't remember any of the drugs really changing so rapidly. And they're better ideas, they're going to be fancier Car-T cells that attempt to get around some of the adverse effects of these and neurologists will retain really important role in following some of these patients, to be sure that these improvements are actually real and durable.
Dr Monteith: Excellent. Thank you so much for this wonderful conversation.
Dr Pruitt: Well, thank you so much for having me. And I hope people do get information from the article. Thanks.
Dr Monteith: Again, today I've been interviewing Dr Amy Pruitt about her article on neurologic complications of cancer and its treatment, which appears in the February 2026 Continuum issue on neurology of systemic disease. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to our listeners for joining today.
Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use 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.

Nearly one in five patients in intensive care units (ICUs) requires neurologic consultation. The neurologic complications of critical illness can be unique to its underlying processes and can persist as independent disease states even after resolution of the inciting critical illness.
In this episode, Casey Albin, MD, speaks with Shivani Ghoshal, MD, author of the article "Neurologic Complications of Critical Illness" in the Continuum® February 2026 Neurology of Systemic Disease 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. Ghoshal is an assistant professor of neurology for the Columbia University Vagelos College of Physicians and Surgeons in New York, New York.
Additional Resources
Read the article: Neurologic Complications of Critical Illness
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
Guest: @ghoshal_shivani
Full episode transcript available here
Dr Albin: The ICU can be such an intimidating place. There's unresponsive patients, there's beeping equipment and a seemingly endless way in which the nervous system can be compromised. But fortunately, today I have the opportunity to speak with Dr Shivani Ghoshal about her paper, Neurologic Complications of Critical Illness, which is going to help us demystify the approach to these patients and provide some clinical pearls that you can take to your next consult in the ICU.
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: Hello, this is Dr Kasey Albin. Today I'm interviewing Dr Shivani Ghoshal about her article on neurologic complications of critical illness, which appears in the February 2026 Continuum issue on neurology of systemic disease. Welcome to the podcast, Dr Ghoshal. It's really such a treat for me to get to interview you, someone who I know and have worked with in the past. But for those who do not know you, please give us a little background about what brought you to this topic and what you do in your clinical life.
Dr Ghoshal: Thank you so much. It's a thrill to be interviewed by someone that I know well and get to work with. Outside of writing this article for Continuum, I am a neurointensivist. I'm an assistant professor of neurology at Columbia University and the program director for the Neurocritical Care Fellowship between Columbia Cornell and New York Presbyterian. So, a lot of what I do in my day-to-day is thinking about acute brain injury along with the neurology of systemic disease and how, really, the two interplay with each other, of how neurologic complications can arise from systemic illness and the other way around.
Dr Albin: Yeah, you are the absolute perfect person to kind of walk us through the complexity of the brain and body connection.
Dr Ghoshal: I don't know if I can deal with that kind of praise, but thank you.
Dr Albin: And you've really written a powerhouse article on just the myriad of complications that really arise in the ICU, and you've broken it down into what I think is a very thoughtful way of sort of bucketing these complications. So, tell us a little bit about the approach you took here.
Dr Ghoshal: I love this article because neurologic complications are just so common in so many types of acute critical illness. And I think we have to think for each organ system, how does this affect the brain, and then how does the brain then interplay, let's say, in kidney failure, in hepatic failure, in sepsis, right? Which is so common that I think we don't even think a lot about, like, what are types of septic encephalopathy for all the antibiotics we give; like, what are the implications of this? I really enjoy taking each system and thinking about, how does it specifically affect neurologic complications?
Dr Albin: Yeah. And then there was a really nice breakdown in terms of some of the procedures that will happen within the ICU in general. You know, the things that are happening to the patients at the bedside also put them at risk for neurologic complications. Then there are those neurologic changes that are happening because of some of the underlying problem that brought those patients to the ICU. And then the unfortunate number of problems that arise because the patient has been in the ICU for such a long period of time.
Dr Ghoshal: You know- and I think that that first part you mentioned, just about procedures in the neuro-ICU, right? Or in the ICU in general. I think that we don't think about that on a day-to-day level, right? Just like arterial lines are one of the most associated with any kind of peripheral nerve injury, especially axillary arterial lines. I learned quite a bit, even going through this article and then looking at other sources. So, thank you also for pointing that part out.
Dr Albin: Yeah. When I was thinking about how do we distill all of what was covered through this article, I actually really thought it would be sort of most interesting to have you model sort of your approach to these patient complications and how you approach the complexity of an ICU patient. And so, if it's okay with you, we'll just walk through a couple cases.
Dr Ghoshal: Oh my gosh, let's do it.
Dr Albin: All right. So, these are all, of course, composite cases. You know, there is no patient violation here. Let's say that this is a 64-year-old patient and they're admitted with influenza, and they develop ARDS. And they're in the MICU. And this patient, they were pretty sick on arrival and they were intubated for three days. But now the patient's been extubated, and the MICU team calls you because today she's having trouble swallowing and her voice, you know, the family says that this is not what she normally sounds like. And the team is really quite worried that she's had a stroke. And so they are calling for a neurology consult because they want to know what they should do. So, walk us through your approach to that patient.
Dr Ghoshal: Well, I think the primary team being concerned for a stroke is definitely reasonable, but I think, taking a bigger step back, what I would first want to think about, is this neurologic or non-neurologic? Neurology, you know, there's a parcel of things we can go through, but even just a non-neurologic, like, is this just primary injury to the vocal cords, right? I think about the cough were there, the ET tube, it wasn't overinflated which caused direct damage, right? And then after that, then I would think a little bit more about my approach for what is going on neurologically. Thinking about either, is this a brain process or is this a- more of like a spinal cord cervical cord injury process or more cranial nerve issue?
Dr Albin: Yeah. How would you approach the exam in that patient?
Dr Ghoshal: Yeah. You know, I- and just to, again, take a step back, right? To remember that when we do intubate someone, the physical maneuvers that we have are a chin lift and regular endoscopy, right? They have, like, significant movement for the cervical spine. So, I might want to know even before I examine the patient, right, or their history, right, do they have anything like, do they have known cervical stenosis? Do they have any, like, cervical spine pathology? Was it a difficult intubation? Right? So, these are the kind of the things I'd want to know even from the history, along with whatever vascular risk factors they may have. And then, to your question about the actual exam. Yes, you know, I may look for, like, crossed findings, right? If we're thinking about, let's say, a medullary lesion, etc. I think all listening to this podcast know about MRI testing there. But beyond what I would be looking for, let's say, in a medullary stroke, I'd also want to be looking at just, like, water paresis, right? I might want to be interested in, let's say, signs of neurogenic shock. You know, you mentioned they're in septic shock, ARDS. I might want to actually take a look to see, like, was this all septic, right? Or what are their other shock types present.
Dr Albin: So, what I hear you're saying is you're evaluating A, first of all, answering the consulting question, you know, is there a real risk for some sort of cerebrovascular phenomenon, but then actually going to the bedside to examine the patient, to say, does that make sense? Do we see hemibody involvement here? And it's a good thing that you're approaching it that way. Because actually, when you go to the bedside, she does have some difficulty speaking. And reading the notes, this was actually quite a difficult intubation. From just the cranial nerve, you know, where she has maybe some dysphonia and dysphagia. But you also, on exam, then find that she's got some pretty symmetric distal weakness in her arms bilaterally. And so, when you find that, what are some of the imaging that you're going to think through to try to pin down exactly what's going on here?
Dr Ghoshal: I love these cases because it's not so straightforward. Now, let's say if she has, like, an upper extremity weakness and lower cranial nerve deficits, you know, things I'd be looking for, like any injury to, like, hypoglossal nerve, vagus nerve. The vagus nerve is going to be hard to tell, right? Recurrent laryngeal nerve, you know, the lingual nerve. I might be thinking more about stretch injury, which we think of as tapia syndrome, right? So, just a textbook answer. The hypoglossal recurrent laryngeal nerve injury. And what we're going to be looking for is dysphonia, dysphagia, and unilateral tongue paralysis. Could be a bilateral as well. But I guess, then, the next question after I'm going through my physical exam findings is thinking about my imaging choice.
Dr Albin: So, for this patient, given that she's got this bilateral upper extremity, maybe some tepia syndrome where there may have been some stretch injury to some of those hypoglossal nerves. She may have also just had some trauma to the vocal cords. Like, as you said, these procedures can really put patients at risk for just mechanical injury to some of those structures. But knowing that upper extremity weakness, what kind of imaging, then, do you look at for the court?
Dr Ghoshal: I think it's not unreasonable to do an MRI brain, right; with that, it then cuts through the brain stem. And then doing an MRI of the cervical spine. I guess the point that you mentioned at the very beginning, that this is three days after she was intubated… you do run the risk beyond 72 hours of, let's say, a primary injury. Let's say if she had, you know, God forbid, an injury to the cervical spine, those hyperintensities, especially when associated with ligamentous injury, they can pseudonormalize beyond that time. I would say yes, absolutely. MRI of the brain, cervical spine, then cuts through the brain stem. But I would worry that if too much time elapses, you may miss some of those injuries that you would otherwise find.
Dr Albin: Yeah. I think those are some really important take-home pearls, and when we're thinking about the cord injury that could occur through the intubation process, that we really do need to be aware of student normalization of the T2 hyperintensities after that 72 hours. And so, I think that's a really important pearl for us to take home. So, kind of summarizing this case here, there was probably a multitude of things going on, which highlights to me the complexity of ICU patients. Less likely in this case, and they did not find a stroke. But that is, of course, something that we must keep on the differential for any critical care, critically injured, critically ill patient. But tapia syndrome where you have some stretch injury to the hypoglossal nerve and the recurrent laryngeal nerve, which can put people at risk for dysphasia or dystonia after intubation. And then that hyperextension injury that can happen for patients who are intubated, because people, especially for difficult intubations, are really having to manipulate the neck. And for an elderly patient who may have some cervical stenosis, that hyperextension can actually result in a central cord syndrome, which is what they discovered with the C-spine MRI in this case. So, cognizant of all of the cervical injuries that might accompany the procedure of intubation.
Dr Ghoshal: And you know what I would say, right. Because I think that our population is overall aging. I think with that, we're going to end up with, like, more cervical spine pathology for these patients that are ongoing intubation, just as you, you know, very astutely pointed out. Right? Trying to have at least, like, manual inline stabilization, right, or even like, considering fiber optic intubation in some of these patients is probably going to be a safer way to go to avoid these kind of injuries.
Dr Albin: Yeah, I think that that's so true and really emphasizes the importance of communication between the neurology team and the critical care team.
Dr Ghoshal: Totally. 
Dr Albin: Neurology is probably not the person intubating the patient. Right? But it's really important for any of these consults to have a good appreciation and that robust communication with the critical care team about what has been going on systemically for this patient, even opening that intubation note and saying, was this an easy intubation? Was it a difficult intubation? I think sometimes we forget that key skill of just communicating across the teams to have a holistic picture of what's been happening in MICU.
Dr Ghoshal: Yeah, I totally agree. It's kind of why my first part of this case you mentioned is just like asking the team, like, what happened during the intubation, right?
Dr Albin: It's a really important takeaway. All right. We're going to shift gears from procedural complications, reminding our listeners there is a fantastic summary of all of the things that can happen to ICU patients, just because we're doing things to them, putting needles in places where needles aren't usually, such as for arterial lines, for central lines, intubating patients; all of these have complications that can affect neurologic function downstream. But let's shift gears and let's talk now about a 72-year-old man. And he's admitted to the ICU with pyelonephritis and bacteremia. He's got nephrolithiasis. And the team calls you because he, like many patients in the ICU, has some, quote, "shaking events." And he's altered, and they want to know what to do.
Dr Ghoshal: So, there's a lot to unpack there. Sepsis is so common, right? When you're saying this patient is altered, sepsis-associated encephalopathy occurs in 70% of patients. So, like, in sepsis or septic shock. And we know that, you know, they say it affects mortality, long-term cognitive outcomes. But because, I think, it's so common, we don't really take the time to think about what is going on in sepsis in the brain.
Dr Albin: The brain is an end organ perfusion. And the end organs are what we're sort of monitoring in sepsis, and the brain is such a key marker of that.
Dr Ghoshal: Absolutely. I think there are a lot of things that happen with sepsis in the brain. But if I were going to pick like 1 or 2 points that I really wanted to hone in on, it's thinking about that blood brain barrier disruption that happens in sepsis. And so, what that does when you disrupt the blood brain barrier is that you end up with this inflammatory milieu, for lack of a better term, that, like, comes into the brain. You have, like, a disordered sort of microglial activation, cytokine release. You know, all of these things are creating more oxidative stress, neuronal damage. And the other hand of this, right, along with that blood brain barrier disruption, is disordered cerebral auto regulation.
Dr Albin: And I think that those two things are probably underappreciated. The complications and why, maybe, they lead to this downstream difficulty in recovering and then probably are also setting the patient up to be at risk of downstream delirium that is so frequent in the ICU.
Dr Ghoshal: I couldn't agree more. And, you know, for this patient's case, right, where you're saying, like, they're altered, they're shaking, I bring up this idea of cerebral autoregulation. Right? Just because for normal patients---or normal people, rather, right?---normal cerebral autoregulation allows us to have, like, stable brain perfusion through whatever range of pressures we have. A lot of these patients are septic; whether they are hypertensive or not, they have significant changes in cerebral vasoconstriction, vasodilation, right? And this can create anything from, let's say, like, neuronal excitotoxicity, metabolic alterations. Right? Just in that setting of cerebral inflammation. So, these patients, yes, are at a very high risk of encephalopathy. And then from these changes, right, from blood brain barrier disruption, whether that's from a cerebral autoregulation or just from that inflammatory milieu, they're at a super high risk of stroke and seizure.
Dr Albin: Yeah. So, they… in calling you to the bedside, someone comes to meet you and they say, we sent a bunch of labs off and we just got one back, and it's his ammonia, and his ammonia is 92. So, do you think that's what's going on here? This is so common. Right? Hyperammonemia. Give us sort of your approach to kind of triaging, is the hyperammonemia really a problem or is it just some sort of bystander?
Dr Ghoshal: Oh, you know, ammonia is such a slippery lab, right? That… well, it's very hard not to have a strong opinion on it one way or the other. And so, I think what I would say is that ammonia can be elevated for, like, a parcel of reasons. Right? Like if someone has tonic colonic movements, you can have ammonia. That's just, like, part of like enteral metabolism, muscle breakdown, whatever it may be. And ammonia can go up for a lot of reasons. And it's true also that ammonia can contribute encephalopathy. And there are a few mechanisms that can go through in a little bit. I would first want to know… a part of understanding, I guess, any lab is understanding in this context of, like, what was the ammonia before? Right? What is their baseline ammonia? Is this a significant rise? Like, how much of a rise should you care about?
Dr Albin: Yeah, absolutely. So, you look back and they live sort of at the upper range of normal with 60 being their sort of baseline.
Dr Ghoshal: Yeah. You know, I don't know that I would be so concerned about this particular ammonia level. I may trend it. But, you know, just to talk a little bit about ammonia and why we care about encephalopathy, right? So, the reason why it's so concerning, I guess I should say, in any kind of acute illness is that ammonia will cross the blood brain barrier. And then it's converted into ammonium ions, and it will go into astrocytes and, like, they can increase interstellar osmolarity. Right? So, these cells swell. Right? And because water is drawn into the astrocytes, they cannot interfere with actual functioning of the astrocytes. Also worsen cerebral auto regulation and cause, I guess, sort of an excitotoxic environment. Right? So, ammonia can be concerning, I think when you send in a lab, right? I think it's important to remember that there's no direct relationship between ammonia level and encephalopathy severity.
Dr Albin: Right. I think that's a really key point to drive home that it's usually not until we're in the hyperammonemic ranges above the 120s-150s up into the high two, three, four hundreds that we really need to be concerned about that cerebral edema and potential, even herniation. But these low-level ammonias, just like you said, like we really need to understand the baseline, how much they've changed, the context of, you know, what the ammonia sent on ice? Was it laying out in the room for hours on end? That really contextualizes this lab that we otherwise have a very hard time interpreting.
Dr Ghoshal: You're absolutely right that an ammonia greater than 120, you know, from our guidelines, both in lymphatic disease along with kidney disease. So, let's say above 120, your patient may be more at risk for cerebral edema. I could also play the devil's advocate and just remind, you know, that because ammonia isn't converted into ammonium in the brain, a peripheral ammonia level really may not reflect central nervous system levels. Right? So, let's say your ammonia is a bit lower also. But let's say there's been a significant change in ammonia for the patient. That may cause some cerebral disturbance that, you know, let's say this ammonia is still below 120. I may still be worried about it just because of the trend. Right? And knowing that my serum level may not really reflect what's going on above.
Dr Albin: That's such a great point. So, lots of pearls around this lab, comes back abnormal all the time. In fact, I feel like it's more frequently abnormal than it is normal in our ICU patients. And so, I really wanted to give residents and listeners a way that we who work in the ICU contextualize that. So, in this case, you've been musing, hmm, this is probably not what's really going on here. He is still having these movements at the bedside. Let me ask you, when you hear shaking in the ICU, what's your big differential there?
Dr Ghoshal: I always want to know, is it something like a myoclonus? Right? Is it something like an actual coordinated movement? Is this also something like a chorea, right? There are so many movements. So, like, I think that Continuum actually in the past put out a great issue about, like, movement disorders in critical illness. But really what I want to know is, like, first of all, like, is this neurologic or not neurologic? Right? Is this a, you know, let's say a seizure? Is this something suppressible, nonsuppressible? I really want to know more about what that movement is before I could even create a differential.
Dr Albin: Totally. And so, when you're in the bedside, he's doing exactly that sort of classic myoclonus. He is having these short, jerky movements. They are not rhythmic. He is intermittently following some commands through this, but inattentive would be the best neurologic term for his mental status state. But then while you're there, he actually does have a GTC and you're in the room. It's generalized, it's convulsive, no longer responsive. His eyes are rolling up and you are well-convinced this truly is a seizure. As you start to approach, now, a seizure in the ICU, walk us through kind of some of the things that you think about in terms of labs you might want, what imaging you might want, what risk factors you're most concerned about.
Dr Ghoshal: It sounds like he's having two distinct types of movement, right? He's having some myoclonus, right, or multifocal myoclonus where he has an intact mental status, for better or worse, through it. On that sort of bucket, I'm thinking more of metabolic disturbances. So, I went through this whole thing about the ammonia. But I think what I'd really want to know is, like, what is happening with his uremia, right? What is happening to his kidney function? I think you mentioned you had nephrolithiasis on top of being, I think, critically ill. I think that's some of the things I'd be looking at. I also would like to know about his antibiotics, any medications he's taking. And then for the seizure, I may want to know some of the similar labs. Right? Even just whatever, like, what is his magnesium? What is his calcium? Like, simple things being simple. And then I can go down a little bit more of a list on what I would do for the actual seizure. Just knowing that sepsis, hepatic disease, renal disease, antibiotics themselves may all increase your risk of having a seizure.
Dr Albin: Yeah, absolutely. And I think what you said about sort of knowing the labs and knowing the medications plays such a crucial role in our workup for ICU changes in neurostatus. And so, in this case, because of that nephrolithiasis, you go scroll through his labs. And it looks like his creatinine has risen to 4 quite abruptly. So, he's got a pretty severe acute kidney injury. And his BUN has risen all the way to 80 over the course of three days. And then you're looking at the med list, and he is on a bunch of antibiotics, but one of them is cefepime. And so, walk us through, with just those couple of key words, what are some of the things that you are thinking about from the neurologic perspective?
Dr Ghoshal: I am, like, salivating. I love these cases. No, I'm serious, right? So, like, I'll take a few minutes at the beginning to talk about, like, uremia and uremic encephalopathy. You know, we see uremia often, and uremic encephalopathy, we think, maybe there's some part of cytotoxic edema, right? Because that urea accumulates in the brain; it accumulates similar to, like, almost ammonia, creates these toxic wanding compounds in the thalamus, like, in the cortex, wherever it may be. And that itself will cause, like, a, let's say, impaired cytokine clearance from the brain, neuronal apoptosis, also affects the blood brain barrier. So, all of these things itself, like, from urea, all right, like a worsening uremia, can cause a different sort of CNS changes that could affect both the seizure side along with the multifocal myoclonus.
Dr Albin: Yeah. Just putting him at risk of two very different types of neuropathology, right in the same case.
Dr Ghoshal: Totally. And you know what I'll say about like, uremia? I could talk about this for a very long time, but like, really what I want people to remember is that uremia really increases your risk of seizure. I talked a little bit about this accumulation of uremia, like a uremic exquisitely in the brain, but you have this metabolic acidosis that develops from urea and you increase the activation of your acid-sensing ion channels. Right? And these retaining creatine metabolite actually cause more inhibition of your GABA receptors and stimulation of your NMDA. Right? So, all of these things together, like I think uremia is so common that we don't really take the time to think about, like, all of these things that could be happening.
Dr Albin: Yeah. And then because of the poor kidney function, there's also accumulation of drugs. And there's this risk for toxic accumulation of some of the things that are sort of more renally metabolized.
Dr Ghoshal: Absolutely. And on top of that, if you include, you know, what we talked about before, let's say you have cortical edema or hypoperfusion or a disordered cerebral autoregulation just from sepsis itself. You know, all of these things do fit together, right? It's not just a one thing for every. I know that you mentioned also there, antibiotic. I loved writing the section on antibiotic-associated encephalopathy, in part because it's something we don't spend as much time thinking about. I will say just broadly, there are three subtypes of antibiotic-associated encephalopathy. The first one, I think, is the most common. That, like, I associate it with beta-lactam, cephalosporins, or penicillin. Right? And that is where we can often see, like, seizure and myoclonus, right? You're really between, like, in days from antibiotic use. We think some of that is just from competitive antagonism of GABA receptors. To quickly talk about, you know, we also have types that are associated with quinolones and macrolides. More of, like, an acute psychosis. And then absolutely metronidazole, which causes a subacute encephalopathy---takes a little bit longer, you know, and more associated with cerebellar dysfunction. But I think every time that I am looking at a patient like this, I am absolutely going through and looking at the antibiotics.
Dr Albin: I love that. And because it's not- cefepime is really the classic, and it's been the poster child for that type-one complication where you get mild blueness and seizure, usually within a day or two of starting the antibiotics---but it's all cephalosporins. It can be any beta-lactam. And so, cefepime is sort of our, like, poster child, but is not the only one. And so, with removing that antibiotic by getting him on a continual renal replacement therapy, this patient actually does quite well. And I think this is a take-home message for all of us, that helping the critical care team limit the risk to the patient from a medication perspective, us helping them say, you know, can we pull this off? Can we switch this to something that's going to be more neuro-friendly from their antibiotic perspective? really can make a huge amount of difference to that patient's long-term outcomes.
Dr Ghoshal: Totally.
Dr Albin: I think that you and I could talk about this all day long. I mean, this is just the, like, bread and butter of these complex patients that we see. But I think I'll summarize it for our listeners that really have to think about what procedures did the patient get, opening some of those notes to figure out where are their complications, and then taking a very holistic approach to the ICU patient and making sure that you're characterizing what kind of abnormal movements are they having? What are their labs? Being mindful about the context the lab was sent in and the patient's baseline, like we talked about with that hyperammonemia, really matters where the patient's been. And then that medication list is- can be culprit number one, two, and three for bad things that are happening to the patient. Again today. I've been interviewing Dr Shivani Ghoshal on her article on neurologic complications of critical illness, which appears in the February 2026 Continuum issue on neurology of systemic disease. Be sure to check out Continuum Audio episodes from this and all other issues. And thank you so much to our listeners and to Dr Ghoshal for joining today. It was a pleasure.
Dr Ghoshal: Thank you for having me.
Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use 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.

Neurologic complications of hematologic disorders are frequently encountered in clinical practice and can involve both the central and peripheral nervous systems. Early recognition and appropriate management in collaboration with a hematologist are essential to reduce morbidity and mortality.
In this episode, Kait Nevel, MD, speaks with Lauren Patrick, MD, and Mark Terrelonge, MD, MPH, authors of the article "Neurologic Complications of Hematologic Disorders" in the Continuum® February 2026 Neurology of Systemic Disease issue.
Dr. Nevel is a Continuum® Audio interviewer and a neurologist and neuro-oncologist at Indiana University School of Medicine in Indianapolis, Indiana.
Dr. Patrick is an assistant professor of neurology at the University of California, San Francisco, in San Francisco, California.
Dr. Terrelonge is an associate professor of neurology at the University of California, San Francisco, in San Francisco, California.
Additional Resources
Read the article: Neurologic Complications of Hematologic Disorders
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Host: @IUneurodocmom
Full episode transcript available here
Dr Nevel: Thick blood, thin blood. These are terms often used by patients and caregivers to describe some of the hematologic disorders that can lead to neurological diseases such as stroke. So, when should we consider a hematologic disorder as a potential cause for neurological conditions, such as stroke or neuropathy. Today I have the opportunity to interview Drs Lauren Patrick and Mark Terrelonge to learn more about neurologic complications of hematologic disorders in their recent article in Continuum.
Dr Jones: This is Dr Lyell Jones, editor-in-chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast.
Dr Nevel: Hello, this is Dr Kate Nevel. Today I'm interviewing Drs Lauren Patrick and Mark Terrelonge about their article on neurologic complications of hematologic disorders. This article appears in the February 2026 Continuum issue on neurology of systemic disease. Welcome to the podcast, and please introduce yourself to the audience.
Dr Patrick: Thank you for having us. We're both thrilled to be here. I'm Lauren Patrick, a vascular neurologist and assistant professor at the University of California, San Francisco, and program director for the Vascular Neurology Fellowship here.
Dr Terrelonge: And I'm Mark Terrelonge, I'm an associate professor of neurology and neuromuscular medicine here at UCSF and one of the associate program directors for the adult neurology residency. Nice to meet you.
Dr Nevel: Nice to meet you both. Really looking forward to getting into your article and learning more. So, to kind of kick us off, I always like to ask what do you think is the most important takeaway from your article for the practicing neurologist? And maybe since there are two of you and I suspect you covered slightly different aspects of this article, maybe you could give us two most important takeaways.
Dr Patrick: Sure. I think the biggest takeaway is to keep hematologic disorders on the differential when evaluating patients with neurologic symptoms. Conditions like sickle cell disease, myeloproliferative neoplasms, or plasma cell dyscrasias and paraproteinemia can cause strokes or peripheral neuropathies, and many have specific and targetable treatments. The early recognition and collaboration with our hematology colleagues can truly change patient outcomes, whether that's by initiating cytoreductive therapy, managing thrombocytopenia, or optimizing antithrombotic therapy.
Dr Nevel: Great. So, this is a really big and diverse topic. As always, I'm going to urge our listeners to read the article because there is a lot of really good stuff in your article that we just don't have time to get into during this interview today. But you cover a lot of different hematological disorders and how they can cause neurological complications. One of the major neurological complications of hematological disorders is cerebral vascular events. So, I'm hoping, Warren, that you can walk us through a little bit. When should we consider workup of potential hematologic disorder as a cause when we see a patient with ischemic stroke, because certainly not all patients with ischemic stroke should be getting a broad hematological disorder work up. So how can we kind of identify early on that there might be something else at play?
Dr Patrick: Absolutely, great question. So, in many cases, the underlying hematologic disorder is already known, such as sickle cell disease or polycythemia vera. But sometimes stroke is the initial presentation or manifestation of the disease. So red flags can include young age, recurrent cryptogenic strokes or thrombosis, and unusual locations like the cerebral venous system. Laboratory clues such as unexplained erythrocytosis, thrombocytosis, thrombocytopenia, or hemolytic anemia should raise suspicion for an occult hematologic disorder. In the setting of acute illness, immune-mediated or heparin-induced thrombocytopenia or thrombotic microangiopathies should be suspected in patients that have hemorrhagic and or thrombotic complications, particularly when relevant lab disturbances are present. Acquired thrombophilia such as anti-phospholipid antibody syndrome should be considered in young patients with autoimmune disease, prior venous or arterial thrombotic complications, or pregnancy morbidity. Now, these are rare causes overall, but they're important to catch because the management can differ dramatically from our typical stroke care.
Dr Nevel: Great. And what are some of the most common inherited or acquired thrombophilias and when should we be sending these labs?
Dr Patrick: The hematologic causes really account for small minority of arterial strokes approximately one to two percent, but among those, sickle cell disease, anti-phospholipid antibody syndrome and the myeloproliferative neoplasms are the most common. Timing of testing is key. So, the genetic thrombophilia panels can be drawn at presentation, but lab values such as protein C, protein S, and antithrombin levels may be falsely low during acute thrombosis, so they're often repeated weeks later. Similarly, for anti-phospholipid antibody testing that should be done at presentation and when positive, confirmed at twelve weeks, since transient positivity can occur with affections or acute events. So, in patients that are already anticoagulated for anti-phospholipid antibody syndrome, testing becomes particularly tricky, especially with lupus anticoagulant assays. Some results need to be interpreted carefully or repeated when feasible. The main message is to collaborate early with our hematology colleagues to guide the timing and interpretation of these studies.
Dr Nevel: Yeah, wonderful. Thank you. I'll ask some similar questions about neuropathy. So when should we consider an underlying hematologic disorder as being the cause for someone's neuropathy?
Dr Terrelonge: So, luckily for a neurologist, then serum protein electrophoresis or an SPEP is already a part of the first pass evaluation for even the most common neuropathies we see, technically already considered every time we do an evaluation. However, we do know that most neuropathies progress very slowly and don't really lead to significant limitations in patient activities of daily living. And for those, the initial workup step, you may not need to do any additional search for any hematologic diseases after that first step. Within patients who start to have more unusual features with their neuropathy, including a rapid progression, early proximal weakness, significant and extremely painful neuropathies, significant ataxia, or new tremor or anything that's kind of outside of the garden variety neuropathy, then you should start to think about a hematologic cause. Additionally, if a patient already has a known hematologic malignancy or process before their neuropathy, there should be some form of assessment to see through exam or electrodiagnostically if the two are correlated. I do have to add one caveat, though, and that's just because someone has a hematologic malignancy or a paraprotein seen in their blood, their neuropathy and the neurologic syndrome don't necessarily have to be causally related. So, we have to do some additional testing to determine if the patient's presentation of the paraprotein are actually linked.
Dr Nevel: Can you walk us through a little bit how we determine if they're associated or just coincidental?
Dr Terrelonge: Yeah. So, for some of the proteins, there's a specific phenotype that will come with the specific protein. For example, an anti MAG proteinopathies or MAG standing for a myelin associated glycoprotein, it usually leads to a distal sensor and motor polyneuropathy where the most distal portions of nerves are affected. So, in that case, people might notice that they have numbness and weakness in their toes and their fingers, and it doesn't follow that typical length dependent pattern. So, in that case, if you have the anti mag neuropathy and the electrodiagnostic signature of an anti mag neuropathy along with the symptoms, you're more likely to think that the two are related then if not.
Dr Nevel: Great. Thank you. And I was hoping you could speak a little bit more about amyloidosis just because I think that that's one that can be really tricky to diagnose. And I see patients, you know, have sometimes more drawn out evaluations or see multiple providers before a diagnosis is reached. So, can you speak a little bit more to how we diagnose amyloidosis in relationship to neuropathy or other neurological conditions and when we should push for more invasive testing like a nerve biopsy?
Dr Terrelonge: So, amyloidosis certainly is a tricky diagnosis. I've been tricked by it and I think most of my neuromuscular colleagues have probably been tricked by it at least once. It's a hard diagnosis to make is it usually requires a pretty high index of suspicion, and also requires a tissue diagnosis to cinch. There're some patients who will come in with a prior history of amyloidosis and they're a little bit easier to figure out if the neuropathy is related. Maybe it's started in their heart or their kidney first and then you can just see if the type of amyloid they have usually deposits in nerve, and that may be enough. But if there's any diagnostic uncertainty, you could go forward with tissue biopsy. But it's patients in which the neuropathy is the first symptom that amyloidosis can be especially tricky to diagnose. It's a primarily light chain disease. So, if you do only an SPEP as a part of your initial neuropathy evaluation, you could miss it. But usually, the patients will have either a severely painful neuropathy, early autonomic dysfunction, or really prominent bilateral carpal tunnel syndrome. So, if they have any of those, usually we'll add in an amyloid workup as a part of that of the rest of the workup, which would include both light chain evaluations to see if there's any increase in Lambda or Kappa light chains and then also biopsy. Biopsy can be of the skin or fat pad first, which have reasonable sensitivity for picking up disease, but they're not necessarily a hundred percent. So if the suspicion remains high in those cases, a nerve biopsy should be considered. And the reason why this is important is that the chemotherapeutic agents that we have now can actually help arrest a lot of these diseases and stop further organ involvement. So, if you think about it, it is important to keep pushing and looking until you find it.
Dr Nevel: Thank you so much for that. And a follow up question to that, once patients are started on appropriate therapy, the diagnosis is made, chemotherapy is started, what's the typical clinical course that you see in terms of their neuropathy? Do you ever see improvement or is it arrest of worsening?
Dr Terrelonge: Usually for amyloid, there is an arrest of disease, but in some patients, they could have some improvement, not necessarily a dramatic improvement, but some patients could see some reversal of symptoms. That may not necessarily be because nerves injured nerves are regrowing, but because of reorganization of nerves to muscle, they could have some strength increases or at least less pain.
Dr Nevel: Yeah, thank you. So, when should we involve a hematologist in aiding in the evaluation of patients we suspect may have an underlying hematological disorder? You guys really outlined very nicely in your article some of the laboratory workup or other workup like you just talked about with amyloidosis. But at what point in that workup should we reach out to our hematology colleagues?
Dr Patrick: I would say almost always. So, these disorders are inherently multi-system and benefit from early co-management. In acute sickle cell stroke, for example, hematology helps direct emergent exchange transfusion. For myeloproliferative disorders they guide cyto reduction and long term antithrombotic strategy. And for antibody mediated or plasma cell disorders, hematology determines disease specific therapies. So, neurology may help with identifying the presentation, but the definitive management is almost always shared with our hematology colleagues.
Dr Nevel: And as you both have mentioned that a lot of times in these cases, their hematologic disorder may be already known before they present with their neurological symptoms. So, I imagine obviously in those cases that a hematologist hopefully is already heavily involved in their care. What do you think is the most difficult aspect of identifying and diagnosing patients with neurologic illness as having an underlying hematological disorder?
Dr Patrick: The hardest part is maintaining a high index of suspicion, especially since hematologic causes account for a very small minority of arterial strokes. Most strokes are from traditional vascular risk factors like you mentioned, or cardio embolism, so it's easy to stop diagnostic evaluation after standard studies have been performed. An example of a challenging case is a patient that's young, they've had recurrent cryptogenic stroke, and they could have antiphospholipid antibody syndrome, but it can be easy to miss if their antibody titers are borderline or if they're already anticoagulated, which would complicate retesting. So, it's about balancing the urge to over-test with recognizing the few cases where identifying A hematologic cause truly changes that management.
Dr Terrelonge: And then on the neuropathy side, probably the hardest part is deciding what's causal and what's coincidence. Monoclonal gammopathy of unknown significance, or MGUS, is really common in older adults, so not every M-spike on an SPEP explains a neuropathy. And even sometimes there's times when the neurologic picture will develop a little bit faster than the hematologic one. So, it's hard to put the two together.
Dr Nevel: Yeah. What's the most rewarding aspect of taking care of patients with complications from their hematologic disorders?
Dr Patrick: It's deeply rewarding when a targeted diagnosis leads to a tangible improvement in that patient's care. For example, identifying A cryptogenic stroke is being due to myeloproliferative neoplasm or an inherited thrombophilia allows us to move from empiric treatment to possible disease specific strategy. It's really gratifying to give patients that clarity, to give them a diagnosis and in some cases prevent future events.
Dr Terrelonge: Agreed. And even on the neuropathy side, almost all of the neuropathies that are hematologically related are treatable. So, it's so satisfying whenever you have a patient with say an anti-MAG neuropathy or Waldenström can start the patient on therapy, and you can see someone who's been having a progressive decline to stability and in those cases sometimes even significant recovery.
Dr Nevel: Yeah, absolutely. Very rewarding when you can identify the problem and make it better. That's what it's all about. So, what are the future areas of research in this area? What do we still need to learn?
Dr Patrick: There's still a lot to learn. I think we need better data on the safety of acute reperfusion therapy and antithrombotic agents, particularly in patients that are at dual risk for bleeding and thrombosis. Other examples, secondary prevention strategies and anti-phospholipid antibody syndrome. What's the best target INR? Do you add aspirin to warfarin or not? All of that is often left up to expert opinion. What's the best management for adults with sickle cell stroke? There are many open questions there. A lot of the protocols that we have in place for sickle cell patients that are adults as derived from pediatric literature and there's vast potential in terms of disease modifying therapies, especially in the fields of sickle cell disease and amyloidosis. And we'll need to reassess how those treatments may change neurologic outcomes.
Dr Terrelonge: I think on the neuropathy side that having some form of new biomarkers to help us clearly know of the neuropathy and that hematologic illness are associated would be very helpful. On the treatment side, a lot of this is really being driven by the hematology space, but new therapies that treat hematologic plasma cell disorders, including some of the new BTK inhibitor, may be incorporated relatively soon into the algorithm for how we treat many of our patients. I'm excited to see what's to come from this.
Dr Nevel: Wonderful. Thank you so much for sharing your knowledge with us today. I know I've certainly learned a lot by reading your article and through our discussion today. Highly encourage our listeners to read your wonderful article, which is a very thorough review of hematologic disorders and neurological complications. Again, today I've been interviewing Dr Lauren Patrick and Dr Mark Terrelonge on their article Neurologic Complications of Hematologic Disorders, which appears in the February 2026 Continuum issue on Neurology of Systemic Disease. Please be sure to check out Continuum Audio episodes from this and other issues. And as always, thank you so much to our listeners for joining today, and thank you so much to Lauren and Mark.
Dr Terrelonge: Yeah, thank you so much for having us.
Dr Patrick: Thank you so much for having us and for highlighting this topic. We hope the issue encourages clinicians to think broadly about hematologic causes of neurologic disease and to continue collaborating closely with our hematology colleagues. It's a complex but very fascinating intersection for both of our fields.
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