Neurology Minute

Dr. Shuvro Roy and Dr. Michael Levy discuss satralizumab for treating relapsing MOGAD, current management challenges, and the encouraging results of this new therapy. Read more about this abstract.

In part two of this series, Dr. Jeff Ratliff and Dr. Gabriela Figueiredo Pucci discuss the lessons and experiences that happen in neurology-related social media interaction. Show citation: Pucci GF, Gheihman G, Albin CSW. Education Research: A Qualitative Analysis of the Role of Social Media in Neurology Trainees' Professional Identity Formation. Neurol Educ. 2026;5(2):e200307. Published 2026 Apr 22. doi:10.1212/NE9.0000000000200307

In part one of this two-part series, Dr. Jeff Ratliff and Dr. Gabriela Figueiredo Pucci shares the most important takeaway about professional identity formation among those actively engaged in neurology communities on social media. Show citation: Pucci GF, Gheihman G, Albin CSW. Education Research: A Qualitative Analysis of the Role of Social Media in Neurology Trainees' Professional Identity Formation. Neurol Educ. 2026;5(2):e200307. Published 2026 Apr 22. doi:10.1212/NE9.0000000000200307

Dr. Gillian L. Gordon Perue discusses asundexian and the OCEANIC-STROKE trial. Show citation: Sharma M, Dong Q, Hirano T, et al. Asundexian for Secondary Stroke Prevention. N Engl J Med. 2026;394(15):1467-1479. doi:10.1056/NEJMoa2513880

Dr. Bradley Ong discusses the use of eptinezumab in combination with patient education is an effective treatment for reducing disease burden in patients living with chronic migraine complicated by medication overuse. Show citation: Jensen RH, Lundqvist C, Schytz HW, et al. Eptinezumab With Patient Education for Chronic Migraine and Medication-Overuse Headache: The Randomized, Placebo-Controlled RESOLUTION Trial. Neurology. 2026;106(8):e214863. doi:10.1212/WNL.0000000000214863

Dr. Shuvro Roy and Dr. Amanda Piquet discuss a brief overview of stiff person syndrome, as well as the trial and the trial results. Read more about this abstract on the AAN website. Show transcript: Dr. Shuvro Roy: Hi, this is Shuvro Roy from the University of Washington and welcome to today's Neurology Minute. I just wrapped a longer conversation with Amanda Piquet from the University of Colorado Anschutz School of Medicine. We were just talking about the recent Phase 2 trial evaluating Miv-cel Kyverna Therapeutics' anti-CD19 CAR T-cell therapy in patients with Stiff Person Syndrome. Amanda, would you mind taking us through a brief overview of SPS as well as the trial and their trial results? Dr. Amanda Piquet: So Stiff Person Syndrome, or SPS, is a rare disabling autoimmune neurologic disease with a major unmet need. About 80% of patients ultimately lose their mobility and we currently have no FDA approved therapies. Existing treatments like IVIG, rituximab, and plasmapheresis are all used off label, often requiring chronic dosing and frequently failing to stop progression. KYSA-8 is a registrational Phase 2 study of 26 patients with refractory SPS. Patients experienced rapid, statistically significant and clinically meaningful improvement across all primary and secondary endpoints. Primary endpoint was the timed 25-foot walk. And this improved by a median of 46% at 16 weeks. Of patients requiring walking aids at baseline, about two thirds no longer needed them by week 16 to complete that 25-foot walk. Some patients who had struggled to walk were even able to run again after treatment. Another key finding was that all patients discontinued chronic immune therapies and remained off treatment as of the last follow-up. From a safety standpoint, miv-cel was generally well tolerated, with no high grade CRS or ICANS observed. In my opinion, these outcomes are unlike anything we've seen previously with Stiff Person Syndrome and may represent a paradigm shift, not only for SPS, but potentially for other antibody-mediated neurologic diseases more broadly. Dr. Shuvro Roy: Just curious, are there any upcoming implications for the application of this treatment for patients, you think, in the coming year or so? Dr. Amanda Piquet: Kyverna, the company who developed miv-cel, has initiated a rolling BLA with the FDA for potential approval and this would be, if approved, the first CAR-T therapy for SPS. So we're anxiously awaiting the outcome of that process. Dr. Shuvro Roy: Fantastic. Amanda, thank you so much for your time. And if you are intrigued and want to know more details behind the findings in the study as well as a conversation around CAR-T therapy for autoimmune neurologic disease as a whole, I encourage you to check out the Neurology Podcast feed for our full conversation there. Thanks for tuning in.

Dr. Stacey Clardy discusses methylenetetrahydrofolate reductase (MTHFR) in this lab minute. Show transcript: Dr. Stacey Clardy: Hi, this is Stacey Clardy from the Salt Lake City VA in the University of Utah. Let's do a lab minute today on MTHFR. This one just simply will not go away. This is one of those topics where a huge amount of patient anxiety is inversely proportional to the utility of a test. So MTHFR is methylenetetrahydrofolate reductase. It's the enzyme that helps generate five methyltetrahydrofolates supporting remethylation of homocysteine to methionine. That biochemistry does matter because the clinical leap that often follows is the problem. So the common polymorphisms of MTHFR are C677T and A1298C. They are widespread in the general population. A recurring misunderstanding is that ordering MTHFR genotyping in a thrombophilia evaluation or as a catchall explanation for you name it, migraines, neuropathy, psychiatric symptoms, nondescript inflammation, is going to give you the answer. The best evidence-based guidance is that MTHFR polymorphism testing has minimal clinical utility and should not be ordered routinely, particularly not as part of a thrombophilia evaluation.So what do we do when a patient arrives with one of these MTHFR results and they are concerned? I try to translate into what actually matters clinically. If there is a concern for thrombotic risk or a documented thrombotic risk event, I focus on established thrombophilias and clinical risk factors and not common MTHFR isolated variants. Now, if the concern is folate metabolism and homocystine, well, we can actually measure those nutritional markers and homocystine. And so if homocystine is elevated, the next thing I'll do is consider the context. And if their folate is low or if one of their B vitamins is low, I replace it rather than building a medical mythology around a genotype that's not going to change the management for most patients. So that's an approach and an update to MTHFR. I hope it's helpful. This is Stacey Clardy, until next time.

In part two of this series, Dr. Andy Southerland and Dr. Dan Ackerman discuss a few rapid‑fire concepts from the 2026 guidelines, focusing on what is new and how emerging data may shape patient care. Show transcript: Dr. Andy Southerland: Hello, everyone. This is Andy Southerland from the University of Virginia. And for today's Neurology Minute, I'm speaking with my friend and colleague, Dan Ackerman, Chief of Neurology and Director of Stroke at St. Luke's University Health System. We've been speaking in the main neurology podcast on tips for updated clinical practice related to the 2026 American Heart Association guidelines for the early management of patients with acute ischemic stroke. I'm going to hit Dan with a few rapid fire concepts that were touched on the guidelines that I think are new or provide some new insights, new based on the data and to how we treat patients. So Dan, you ready for it? Rapid fire, acute stroke treatment decision making? Dr. Dan Ackerman: Absolutely. Hit me. Dr. Andy Southerland: All right, Dan. I'm a resident going to my first stroke alert on July one this year and I've got a patient coming in, they're having disabling stroke symptoms and they're, in every other way, eligible to receive thrombolysis, but they have a history of paroxysmal atrial fibrillation. They are on apixaban and they took a dose of that apixaban. They forgot to take one yesterday, but they took one the day before, had the evening before. And so 36 hours ago, they took a dose of their apixaban. So based on previous dogma, I think prior guidelines might've said if it's within that 48 hour window, that's a relative contraindication of thrombolysis. What, say, you based on the new guidelines and then how do they inform us about making that decision? Dr. Dan Ackerman: I would actually say the new guidelines are a little bit more aligned with what you just said. You mentioned it as a relative contraindication to thrombolysis. I think before these guidelines came out, a lot of people would've said, "No, that is a strict contraindication to thrombolysis." And a lot of folks would run a stroke code or a stroke lid a little slower knowing that, hey, this person is on, whether it's apixaban, rivaroxaban, edoxaban, dabigatran, et cetera, any of these direct oral anticoagulants and say, "Well, no, we know that person's not a candidate for thrombolytics." Well, no, the newer guidelines would suggest that that is a relative contraindication, not a strict contraindication. And when we look back at studies on this, it has not been suggested that there is a big contribution in terms of exactly how long ago that last dose was. Was it two hours ago, 12 hours ago, 20 hours ago? And there has not been shown to be a clear benefit of testing for factor Xa activity levels, bleeding time and the like. So the guidelines do suggest that, hey, we need more data on this. It's not to, say, that this is 100% perfectly fine. Remember, that's a relative contraindication, so it's still a risk benefit discussion, but studies have not shown an increased risk for hemorrhagic complications in patients who have had recent DOAC exposure who receive IV thrombolysis otherwise according to the guidelines. So I would tend to offer it in that situation and make sure that we document what drugs someone's on, how long ago was their last dose, all of this kind of information in addition to what we might normally otherwise get down. Dr. Andy Southerland: Does that change, Dan, if they took the DOAC in the last 24 hours or even 12 hours? They took it last night, and they're presenting in the morning with their stroke-like symptoms? Dr. Dan Ackerman: The guideline just suggests less than 48 hours, and the data, to my knowledge, doesn't really delineate, at this point, any particular timeframe where we would say, no, there's a cutoff there at two hours or eight hours or 12 hours. So at this point, I would not use that as a way to decide not to offer thrombolysis based on that timeframe. Dr. Andy Southerland: Fair enough. I think that's very reasonable. And I think, again, it's always a good conversation to have either with your attending, if you're that resident on July 1, but particularly with the patient and their family on the risk-benefit of what we know based on the data. Well, that's all the time we have for this Neurology Minute. We hope this discussion will continue to help everyone out there in the hyperacute management of patients with acute ischemic stroke, making those difficult treatment decisions. Good luck.

In the third episode of this series, Dr. Stacey Clardy discusses treatment options and ongoing management. Show transcript: Dr. Stacey Clardy: This is The Neurology Minute. I'm Stacey Clardy from the Salt Lake City VA at the University of Utah. This is the third episode today in our four-part series on Rett syndrome, and we're going to talk about treatment options and ongoing management. There is still no curative therapy for Rett syndrome and management remains largely supportive and multidisciplinary. But there is now an FDA-approved treatment, trofinetide, for adults and children two years of age and older with Rett syndrome. Trofinetide is a synthetic analog of glypromate. It's thought to modulate neuroinflammation and synaptic function, right? Because Rett syndrome involves difficulty with synaptic function. Clinical trials demonstrated improvements in some of the core Rett symptoms, but of course, as always, treatment decisions are going to require an individualized discussion, particularly given some common adverse effects such as diarrhea and vomiting. Beyond disease-specific therapy, management remains symptom driven. Given that epilepsy is common and may be refractory, careful EEG correlations are often necessary. Of course, the breathing abnormalities like hyperventilation and apnea are fairly characteristic and can fluctuate over time so need to be monitored, and gastrointestinal dysfunction, nutritional challenges, other sleep disturbances, and scoliosis require ongoing monitoring and intervention when relevant. Rehabilitation therapies, physical, occupational, and speech, are foundational throughout life. A key principle here is anticipatory management, right? Many of the complications, like cardiac conduction abnormalities and bone health issues, can be identified early and addressed early with better outcomes when Rett syndrome patients have coordinated care. That's it for today. Be sure to listen to the other Neurology Minute episodes in this series on Rett syndrome, and check back for our next and final episode, where we will cover care team essentials and multidisciplinary management. I'm Stacey Clardy for the minute.

Dr. Casandra MacLeod discusses central retinal artery occlusions, recent trials, and those anticipated in the future. Show citation: Préterre C, Gaultier A, Obadia M, et al. Intravenous alteplase versus oral aspirin for acute central retinal artery occlusion within 4·5 h of severe vision loss (THEIA): a multicentre, double-dummy, patient-blinded and assessor-blinded, randomised, controlled, phase 3 trial. Lancet Neurol. 2025;24(11):909-919. doi:10.1016/S1474-4422(25)00308-4 Poli S, Grohmann C, Wenzel DA, et al. Early REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION): Study protocol of a phase III trial. Int J Stroke. 2024;19(7):823-829. doi:10.1177/17474930241248516 Ryan SJ, Jørstad ØK, Skjelland M, et al. A Randomized Trial of Tenecteplase in Acute Central Retinal Artery Occlusion. N Engl J Med. 2026;394(5):442-450. doi:10.1056/NEJMoa2508515 Show transcript: Dr. Casandra MacLeod Hello, this is Casandra MacLeod, a neurology resident at Cleveland Clinic with today's Neurology Minute. Today we will be discussing central retinal artery occlusions, or CRAOs, and the recent trials that have come out and even those further on the horizon. The 2026 American Heart Association and American Stroke Association guidelines for the early management of patients with acute ischemic stroke were recently published and in them highlight the uncertainty around the treatment of acute CRAOs with intravenous thrombolysis, even when the patient presents within four and a half hours and is otherwise eligible. These guidelines come after two recent trials, which we will further discuss. The thrombolysis in patients with acute central retinal artery occlusion, or the THEIA trial, was published in the November issue of Lancet Neurology. This multicenter trial out of France randomized 70 patients with acute CRAOs presented within four and a half hours of time from last known well to either receive IV alteplase and oral placebo or IV placebo and oral aspirin. While safety measures showed no symptomatic hemorrhage event, although they did have one asymptomatic intracerebral hemorrhage occur, the primary outcomes, which included visual acuity improvement at one month, showed some evidence for a trend of improved acuity in the IV thrombolytic group at 66% compared to 48 in the aspirin group, it did not reach significant. And now more recently, the Tenecteplase in central retinal artery occlusion study, or TenCRAOs, was published in the January 2026 issue of The New England Journal of Medicine. TenCRAOs was a six European country multicenter trial that randomized 78 patients with CRAOs all presenting within four and a half hours of time from last known well to either receive IV Tenecteplase or aspirin, both with placebo-matching as in THEIA. The primary outcomes of TenCRAOs also included visual acuity at one month, but unfortunately this trial also did not show [inaudible 00:02:07]. They showed 20% in the IV TNK group compared to 24% in aspirin. And additionally, there was one fatal intracerebral hemorrhage in the TNK group that should be considered. Overall, the AHA and ASA guidelines state the usefulness of treatment with intravenous thrombolysis is uncertain. And this is based largely on these studies as neither trial showed improved visual recovery. Although both of these trials are underpowered, leading many to believe that the jury is still out on the use of IV thrombolytics in CRAOs. But importantly, stay on the lookout for one last trial. The early reperfusion therapy with intravenous alteplase for recovery of vision and acute central retinal artery occlusion, or the Revision trial, is actively recruiting. Revision is similar in design as THEIA, but with a goal of up to 422 total patients for a goal of a well-powered study to guide decision making.

In the second episode of this series, Dr. Tesha Monteith and Dr. Peter Goadsby discuss the prediction of treatment responses for personalized medicine. Show transcript: Dr. Tesha Monteith: Hi, this is Tesha Monteith with The Neurology Minute. Today I'm speaking with Peter Goadsby from the Division of Biomedical Sciences at King Abdullah University of Science and Technology about key trends in headache medicine and some of the most impactful research presented at the AAN annual meeting. Can you talk a little bit about prediction of treatment response for personalized medicine? Dr. Peter Goadsby I hope that AI gives us some direction. I haven't seen anything yet, but I don't think we've done enough with it to make it stunning yet. I think that the AI systems ... I'd love to know, for example ... I've been using triptans for 30 years and apart from using sumatriptan first when [inaudible 00:00:51] had a triptan simply because it's the commonest triptan, which is generally what I do, that's a pretty naff rule when you think about it. I'd like to think that AI systems could work out where we should be going in terms of acute therapy, preventive therapy, whether there are particular red flags or amber flags you might say in a person's broad history. I don't think we've got there yet, but I actually think we will get there. I think we'll be surprised and we'll learn things about the biology of the disorder and about the pharmacology of these medicines, which must have subtle differences because we all see people who respond to one and don't respond to another, and you sort of scratch your head, but you're happy that it happens. Dr. Tesha Monteith: I agree with you, and I think the future is really bright for headache medicine and the potential of AI to move the needle. Peter, thank you again for joining us and sharing your insights. I really appreciate you being on. This is Tesha Monteith. Thank you for listening to The Neurology Minute.

Dr. Margarita Fedorova discusses whether a vaccine ingredient is quietly protecting the brain. Show citation: Taquet M, Todd JA, Harrison PJ. Lower risk of dementia with AS01-adjuvanted vaccination against shingles and respiratory syncytial virus infections. NPJ Vaccines. 2025;10(1):130. Published 2025 Jun 25. doi:10.1038/s41541-025-01172-3 Show transcript: Dr. Margarita Fedorova: Welcome to Neurology Minute. My name is Margarita Fedorova, and I'm a neurology resident at the Cleveland Clinic. Today we're exploring a study that raises a compelling question. Could a vaccine ingredient be quietly protecting the brain? A recent study by Taquet et al., published in npj Vaccines in 2025, investigated whether vaccination with an AS01-adjuvanted vaccine is associated with a lower risk of dementia. You might know it as the immune-boosting ingredient in Shingrix, the shingles vaccine, and Arexvy, the new RSV vaccine. We already know from prior work that the Shingrix vaccine was associated with a reduced risk of dementia, but the question this paper asks is why. Is it because preventing shingles itself protects the brain, or is there something specific about the adjuvant that's doing the work? To answer this, the researchers used a large US electronic health record database comparing over 35,000 people who received the AS01-adjuvanted RSV vaccine, over 100,000 who received the AS01-adjuvanted shingles vaccine and over 78,000 who received both. Each matched against individuals who got the seasonal flu vaccine instead. The findings were interesting. People who received the RSV vaccine had a 29% lower risk of new dementia diagnosis over the following 18 months. Those who received the shingles vaccine had an 18% increase in time without dementia, and those who received both had a 37% increase in dementia-free time. Here's a key insight. Both vaccines target completely different viruses, but both contain the same adjuvant. The fact that a similar protective signal was seen with both suggests the benefit may not be about which virus is prevented, and it may be about the AS01 itself. Why might an adjuvant protect the brain? AS01 contains two active components, monophosphoryl lipid A, known as MPL, and QS21. Together they activate macrophages and dendritic cells, triggering cascade that includes a production of interferon gamma. In animal models, stimulation of a receptor called toll-like receptor 4, which MPL activates, has been shown to reduce Alzheimer's-like pathology. The authors also point out that the protective effect appears within just a few months of vaccination, which is hard to explain purely by prevented infections and may point instead to a direct immunological mechanism. Very important caveat. This is an observational study, not a randomized trial, so we can't prove causation. There was also uncertainty about which brand of RSV vaccines some patients received, which could affect the strength of the AS01-specific conclusion. And with all of the dementia studies, it's unclear whether the vaccines prevent dementia or delay its onset. Though even a delay would be clinically meaningful given how few tools we have. What does this mean for clinical practice? For now, it doesn't change your vaccination recommendations. Both Shingrix and Arexvy already indicated in appropriate patients for the primary purposes, but it adds an intriguing possible benefit when counseling patients who ask about vaccines. And it opens the door to a genuinely exciting question. If AS01 has neuroprotective properties, could it be studied in a therapeutic target in its own right? That's the Neurology Minute for today. Keep exploring and we'll see you next time. If you want to read more, please find the paper by Maxime Taquet, et al., titled Lower Risk of Dementia with AS01-Adjuvanted Vaccination Against Shingles and Respiratory Syncytial Virus Infections, published in npj Vaccines in June 2025.