Advances in immunotherapies for multiple sclerosis and related disorders have increased the risk of infections and raised important questions about vaccination efficacy. This episode reviews infection risks across treatment classes, emphasizes the importance of monitoring and patient education, and discusses optimal vaccine timing to preserve protective immune responses. In this episode, Aaron L. Berkowitz, MD, PhD, FAAN, speaks with Avindra Nath, MBBS, FAAN, coauthor of the article "Infection Risk and Vaccine Considerations in Multiple Sclerosis and Related Disorders" in the Continuum® April 2026 Multiple Sclerosis and Related Disorders issue. Dr. Berkowitz is a Continuum® Audio interviewer and a professor of neurology in the Department of Neurology at the University of California, San Francisco, in San Francisco, California. Dr. Nath is the chief of the Section of Infections of the Nervous System at the National Institute of Neurological Disorders and Stroke, National Institutes of Health, in Bethesda, Maryland Additional Resources Read the article: Infection Risk and Vaccine Considerations in Multiple Sclerosis and Related Disorders Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Full episode transcript available here Dr Berkowitz: Over the last decades, there has been a revolution in the treatment of multiple sclerosis, neuromyelitis optica spectrum disorder, and other immune-mediated neurologic conditions with countless new, highly effective medications. However, with every new treatment comes new risks; and in the case of immunomodulatory therapy, many of those risks relate to infection. Today, I have the privilege of talking with an expert on this topic, Dr Avindra Nath, about the infectious risks of treatments for multiple sclerosis and other immune-mediated neurologic disorders. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Berkowitz: This is Dr Aaron Berkowitz, and today I'm interviewing Dr Avi Nath about his article on vaccine considerations and infection risk in multiple sclerosis and related disorders, which he coauthored with Dr Amit Bar-Or. This article appears in the April 2026 Continuum issue on multiple sclerosis. Welcome to the podcast, Dr Nath, and could you please introduce yourself to our audience? Dr Nath: Thanks very much for inviting me to this podcast. I'm absolutely delighted to have the opportunity to discuss our areas of interest and expertise related to infections and vaccinations for MS patients. My area has been studying the infections of the nervous system since the beginning of the AIDS pandemic, and over the years and decades, we've developed expertise related to various types of CNS infections. That includes ones that are developing in individuals who have immune compromise due to a variety of different reasons. Dr Berkowitz: Fantastic. Well, glad to have the opportunity to speak with you today. When I was in medical school---and you were my attending, actually, we were just reminiscing, which we probably think was not that long ago, but is now over twenty years ago---there were just two medications for MS, right? Beta interferon and glatiramer acetate. And now we have over a dozen, and it's amazing to think of all the progress in these last two decades, as well as for related diseases like NMO. I don't think we even had the aquaporin-four biomarker, right, when I was working with you as a med student in the early 2000s. Dr Nath: And that certainly dates me a lot. Dr Berkowitz: Both of us. Dr Nath: Yeah. Dr Berkowitz: Of course, with all these new treatments, these have been amazing advances for our patients, right? But these come with new treatment-related risks to monitor for with the immunomodulatory medications for MS and related disorders. And one of those most important risks is that of infection. So, your article reviews the potential infectious complications of medications used to treat MS, NMO, etc, and also covers considerations related to thinking about vaccines in this patient population. So, as the MS treatment landscape grows, I can say as a general neurologist, keeping up with all these medications and what to screen for and what to worry about and when to vaccinate just becomes more challenging every year. And your article has so many helpful tables, some organized by medicine, some organized by- sorry, medication, some organized by infection, some by vaccines. So, this is gonna be a great resource for our providers to print out and tape up in their clinic rooms. We won't be able to get into all the depth and detail that you have in this article today, but I do want to focus on some of the key points here related to the common medications we use for MS and which infections to think about and which vaccine considerations we might need to keep in mind for these medications. But before we delve into the drugs, I just wanna ask you more broadly, you talk in the article about the challenge of patients with immune-mediated diseases who are on immunomodulatory therapy being at risk for both flares of their disease and for infections; and these infections can present somewhat atypically, right, in immunomodulated hosts, to maybe coin a term you can correct me on, because they can't mount the full inflammatory response. So how do you approach new symptoms in patients on these immunomodulatory medicines as far as distinguishing disease flare from a treatment-related infection? Dr Nath: So, I have to say that although a lot of new treatments have come along for MS, and they've really, you know, improved the outcome tremendously and there are so many different options, it has also kept people like me relevant because they cause a lot of various types of infections, and so keeps me in business all the same. But just as you mentioned, there's so many of them, even I have difficulty keeping track of what does what. So, you do need to be able to refer back to published literature, and the tables, I hope, will be quite useful in that regard. You're absolutely right, and you can get new infections, you can get reactivation of existing infections, and you can get atypical presentations of various types of infections that you may not normally think of. So that presents multiple challenges to the treating physician. The other interesting thing about MS is, just as you mentioned, that you already have CNS lesions to begin with. Now, on top of it, you have an infection, so now how to sort out what is the existing disease and what is the infection, it can again become challenging. But one thing is for sure: all these infections are caused by an organism. So, what you really need to do is, the underlying diagnostic is to demonstrate the presence of the organism. Whether you demonstrate it depending on the infection in the spinal fluid or in the brain or, you know, some peripheral organ system, that is going to be key to making the diagnosis. So, all your clinical acumen is good, but that alone may not be sufficient. Dr Berkowitz: Very good. So, when you see a, a patient now who has a new neurologic symptom in the context of an immune-mediated disease who's on immunomodulatory therapy, what goes through your mind? Are you thinking this disease and this drug, and sort of what are the infections, and does the syndrome match? Or are you thinking, you know, you can't always rely on the imaging to distinguish between, say, a flare of an MS and PML because white matter lesions could look similar? How do you sort of approach this scenario when it comes up? Dr Nath: So, you're right. You have to keep an open mind so that even though you know some infections are more likely to occur with certain types of medications, that doesn't mean that others cannot occur. So, I think when you first see the patient, you should not jump to conclusions, but rather have an open mind. But yes, for example, your patient is on natalizumab, the chances of PML are going to be high. It's a very interesting drug. It does not cause immune compromise in the periphery, but what it's doing is preventing these cells from getting into the brain. So, because then it's acting at the blood-brain barrier. So that means that organisms that are already present in the brain have an opportunity to get reactivated. Turns out you don't have a lot of organisms in the brain, except JC virus seems to be one of them that does somehow, in some individuals, manage to reside out there. And so that can get reactivated. It can get reactivated in the periphery and then enter the brain, too. So, where the very specific mutations have to occur in that virus in order to take residence in the brain. That would be a suspicion that you might have, and MRI can be useful in, again, helping you think about that possibility. If you have typical lesions involving the U fibers, they're demyelinating, usually you do not have much edema around them because patient is immune compromised, but certainly within the brain in these individuals. And so, then you need to demonstrate the organism. The demonstration of the organism should be in the spinal fluid and not in the blood because in the virus, it can-- is reservoir in the kidneys and in the lymph nodes, and periodically it'll shed into the blood. Detection of the organism in the blood can be a false positive, but in the spinal fluid, it shouldn't be there unless you ha