Avsnitt
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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.
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In part three of this series, Dr. Aaron Zelikovich discusses the clinical outcomes seen during and after the acute infection and how these findings can guide physicians in counseling their patients.
Show citation:
Solomon T, Hooper C, Easton A, et al. Safety and efficacy of adjunct dexamethasone in adults with herpes simplex virus encephalitis in the UK (DexEnceph): a multicentre, observer-blind, randomised, phase 3, controlled trial. Lancet Neurol. 2026;25(2):136-146. doi:10.1016/S1474-4422(25)00454-5
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Saknas det avsnitt?
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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
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In part two of this series, Dr. Stacey Clardy and Dr. John Ney discuss the primary limitation of using claims data to estimate wait times for neurology services, particularly in rural areas or for subspecialty neurology care.
Show citation:
Laffargue EK, Van Der Goes DN, Wilson AM, Parziale SD, Sico JJ, Ney J. Neurology Wait Times After Primary Care or Emergency Department Visits Among the Commercially Insured Population in the United States: 2019-2023. Neurology. 2026;106(10):e218008. doi:10.1212/WNL.0000000000218008
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In part two of this series, Dr. Stacey Clardy and Dr. John Ney discuss the primary limitation of using claims data to estimate wait times for neurology services, particularly in rural areas or for subspecialty neurology care.
Show citation:
Laffargue EK, Van Der Goes DN, Wilson AM, Parziale SD, Sico JJ, Ney J. Neurology Wait Times After Primary Care or Emergency Department Visits Among the Commercially Insured Population in the United States: 2019-2023. Neurology. 2026;106(10):e218008. doi:10.1212/WNL.0000000000218008
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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
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In part one of this series, Dr. Stacey Clardy and Dr. John Ney break down the difference between mean and median wait times for new neurology appointments.
Show citation:
Laffargue EK, Van Der Goes DN, Wilson AM, Parziale SD, Sico JJ, Ney J. Neurology Wait Times After Primary Care or Emergency Department Visits Among the Commercially Insured Population in the United States: 2019-2023. Neurology. 2026;106(10):e218008. doi:10.1212/WNL.0000000000218008
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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
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Dr. Madeline Russell discusses a common complication faced by patients with acute ischemic stroke.
Show citation:
Schwarz G, Cascio Rizzo A, Ambler G, et al. Contrast-Associated Acute Kidney Injury After Thrombectomy for Ischemic Stroke: Prognostic Impact and CAN-REST Predictive Score. Neurology. 2026;106(6):e214655. doi:10.1212/WNL.0000000000214655
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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
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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.
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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.
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In the fourth episode of this series, Dr. Stacey Clardy discusses care team essentials and working within multidisciplinary teams.
Show transcript:
Dr. Stacey Clardy:
This is the Neurology Minute. I'm Stacey Clardy from the Salt Lake City VA and the University of Utah. This is our 4th episode in our four-part series on Rett syndrome. Today we're going to discuss care team essentials and working within multidisciplinary teams.
Rett syndrome requires coordinated, ongoing, multidisciplinary care across the lifespan. So core team members will often include neurology, genetics, developmental pediatrics, gastroenterology, pulmonology, cardiology, orthopedics, and a range of rehabilitation specialists.
Speech language pathology especially plays a central role, particularly through augmentive and alternative communication strategies, given the characteristic profound expressive language limitations in Rett syndrome. Care coordination obviously is essential, and neurologists will usually serve as the central point of integration, helping families navigate the complexities of care systems internationally and anticipating who might need to be brought in at certain times, given evolving needs.
And caregiver input is especially critical in Rett syndrome patients because the patients have limited verbal communication. So it's these caregivers who are going to be able to provide key insights into daily neurologic status, behavior, and subtle clinical changes that clinicians may well not be able to detect in periodic short office visits. Another essential component is transition planning, right?
As Rett syndrome patients age, structured transition from pediatric to adult care systems is necessary, essential to maintain continuity and avoid fragmentation. And as in any rare disease, many families find that participation in specialty clinics, and registries, and clinical trials, when available, can provide access to evolving therapies and contribute to ongoing advances in the field.
That's it for our Rett syndrome series. Be sure to listen to the three prior Neurology Minute episodes on Rett syndrome for a full overview. I'm Stacey Clardy for the Minute.
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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.
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In the June episode of the President's Spotlight, Dr. Jason Crowell and Dr. Natalia Rost discuss the sense of community present within the AAN.
Stay informed by watching the President's Spotlight video.
Show transcript:
Dr. Jason Crowell:
This is Jason Crowell with today's Neurology Minute. Once again, this month for our presidential spotlight, we have Natalia Rost joining us. Natalia, thanks so much for your time today.
Dr. Natalia Rost:
Hi, Jason.
Dr. Jason Crowell:
So what is on your mind this month, Natalia?
Dr. Natalia Rost:
Well, if you remember, last month we talked about our annual meeting, and since I've been thinking about AAN's value of community. Community is top of mind because staying connected, of course, sharing questions, experience, and ideas is how we keep improving care and advancing the field, but also how we elevate wellness for all of us.
Dr. Jason Crowell:
I'm sure there are many different ways we could talk about this sense of community showing up within the AAN, but what are you thinking of specifically?
Dr. Natalia Rost:
Well, of course, we love our annual meeting reunions, but one way we thrive as a community all year long is online through our AAN member sections. As you know, sections are our AAN vibrant member-led groups and each has a dedicated community on Synapse, our online community platform and mobile app. What you'll find there is discussions, resources, announcements, events, and peer Q&A.
Dr. Jason Crowell:
So can you give us some examples of how these sections work and how people participate?
Dr. Natalia Rost:
Yeah. Sections is our online community and our response onto how our field moves fast and sections are where you can stay connected and share knowledge. Every section is dedicated to a different subspecialty or interest. No matter where your focus is, there's probably an AAN online community. For instance, with my specialty in vascular neurology, I can connect with other members in the stroke and vascular neurology section. The topics can range from a tricky case question sharing a protocol or a career advice thread and we've done that for years now. But I'm also passionate about humanities and art, and so I can also explore the interface between neurology and the arts in my neuro-humanities synapse community. I highly recommend it.
Dr. Jason Crowell:
Are there any practical real-life benefits that members talk about when they're discussing these sections, and who all is behind the scenes making this work happen?
Dr. Natalia Rost:
Yeah. In addition to staying in touch all year long, many of our sections also host collaborative sessions during the annual meeting through section showcases. These are discussion-based sessions where sections present untimely topics. And if you're interested, I recommend joining a section now so you can stay on top of the advances for 2027. And for additional context, we also have 80-plus section leaders. These members offer their time and expertise to help their communities thrive, and so we're extremely grateful to them for their leadership.
Dr. Jason Crowell:
So if we have listeners today who are members of the AAN, but they've never gotten involved in these sections, where would you direct them? I imagine they can find information on the AAN website.
Dr. Natalia Rost:
Yes. So very simple. Any AAN member can join sections and access their communities on Synapse. Go to aan.com/sections and access them anywhere by downloading our Synapse mobile app. And my advice is very simple. Find your people, stay current, and bring your questions. Your section community is there year-round.
Dr. Jason Crowell:
Terrific. Natalia, thanks so much for sharing this with us.
Dr. Natalia Rost:
Thanks for having me.
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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.
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In part one of this series, Dr. Andy Southerland and Dr. Dan Ackerman discuss what stands out in the latest thrombolysis guidelines, how these decisions are applied in stroke center practice, and how to educate residents and fellows on incorporating new evidence into treatment choices.
Show transcript:
Dr. Andy Southerland:
Hi. 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. I've been speaking with Dan on the main neurology podcast regarding updates to acute stroke treatment related to the 2026 American Heart Association guidelines that came out in late January of this year on the early management of patients with acute ischemic stroke.
For our episode today, we might focus our discussion around thrombolytic therapy thrombolysis, which is at the core of what we do as acute stroke neurologists when it comes to treatment decision-making. So maybe as a first prompt, Dan, when you look at these guidelines, what stands out to you as you're thinking about how you practice, how you all are practicing at your stroke center, and then specifically how we educate our residents, our fellows on what they need to know, particularly the newness of it when it comes to making thrombolysis treatment decisions?
Dr. Dan Ackerman:
With all the discussions we've had in the past, there have been a lot of specifics about certain studies and how they might affect practice, but this guideline really opened up a lot and gave us an opportunity to do things in a way that makes really good clinical sense and really brings a lot of practices that have now become common at some centers into the fore so that we can get that information out to everyone and make sure everyone has that same really high level of stroke care everywhere they go.
I think the first thing that stands out to me is what did not change. And want to reinforce that, particularly for people who are just getting into this, stroke alert is a screening tool, not a severity score. It's not like an MI alert where you do an EKG and you see the tombstone wave and you say, "Oh, there's an MI and we're taking them to treatment." This is a screening tool, so it is meant to be highly sensitive at the cost of being specific.
At our shop for a long time now, we have initiated stroke alert for anyone who presents either within 24 hours of acute onset of neurologic symptoms or has an unknown onset of acute neurologic symptoms and they are still symptomatic to some degree at the time of their presentation, and that's it. We don't make any other statements about how severe something is or what kinds of symptoms someone necessarily has to have. We purposely keep it as broad as possible, again, because we're trying to screen.
And the other thing that has not changed, time is still brain. So with all of these different nuances on how we can treat patients and who might be candidates for intervention, it is still a matter of understanding these guidelines, applying our best evidence, but doing it as quickly as possible to make sure that we are rescuing as much of that ischemic penumbra as we possibly can.
Now, aside from that, in terms of what stands out that is different, I think one of the early things for me are the recommendations for extended time window for IV thrombolysis. So when you look at the original studies, we understand that when you get out beyond four and a half hours, if you just take all-comers, the risk is going to start to outweigh the benefit. But that doesn't mean there's zero benefit or that no one would receive benefit, but it's a question of, well, how do we cherry-pick those patients who may still receive benefit? And there are a few real specifics in the guideline that help us figure that out.
One is for patients who have an unknown time of onset, but they're within four and a half hours of symptom discovery. And for those patients, they would suggest that doing a stat MRI and comparing a DWI lesion with the corresponding area flare to determine if you see DWI hyper-intensity and the flare image is nice and normal, that would suggest that stroke is young enough that it may still be appropriate to treat that patient.
But we would also say for folks who have salvageable ischemic penumbra, so again, brain at risk that is not core yet, who either awoke with stroke symptoms within nine hours from the midpoint of sleep or, and this is the kicker, are within four and a half to nine hours from last known well. So in other words, they may have been symptomatic already for more than four and a half hours. If those patients have an appropriate ischemic penumbra, it may be reasonable to treat them with IV thrombolysis to improve functional outcomes.
Dr. Andy Southerland:
Well, that's all for this Neurology Minute. We hope this vibrant conversation will help all those who are out looking to make the best treatment decisions for their patients, both based on established evidence and most recent evidence in our new guidelines.
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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.
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Dr. Margarita Fedorova discusses the effectiveness of shunting for idiopathic normal pressure hydrocephalus.
Show citation:
Luciano MG, Williams MA, Hamilton MG, et al. A Randomized Trial of Shunting for Idiopathic Normal-Pressure Hydrocephalus. N Engl J Med. 2025;393(22):2198-2209. doi:10.1056/NEJMoa2503109
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 reviewing a randomized trial that provides high quality evidence for treatment we've been using for decades, shunting for idiopathic normal pressure hydrocephalus. The PENS trial, a placebo controlled effectiveness and iNPH shunting trial was published in the New England Journal of Medicine in December 2025 by Luciano and colleagues. This international multicenter study enrolled 99 patients across the United States candidate in Sweden. While idiopathic normal pressure hydrocephalus or iNPH is characterized by triad of gait impairment, cognitive decline in urinary continence, these findings can be non-specific and we mass factor in radiological findings too. Furthermore, while CSF shunting has long been the standard treatment, its effectiveness has never been rigorously confirmed in a large well-powered randomized trial. In this trial, patients with a clinical improvement in gait velocity after temporary CSF drainage were deemed eligible for shunting and randomizing the trial.
What makes this trial particularly elegant is its blending strategy. All 99 participants underwent the same surgical procedure with the same commercially available programmable shunt valve. After surgery, the valve was set either to an open functioning position or to a high resistance placebo setting. Neither patients nor assessors knew who had a working shunt. This is about as close to a true double-blind design as neurosurgery can get. The primary outcome was changing gait velocity at three months. The open shunt group improved by 0.23 meters per second on average, while the placebo group showed essentially no change in 0.03 meters per second. That's a treatment difference of 0.21 meters per second, both statistically significant and clinically meaningful. To put that in perspective, a change of 0.10 meters per second is considered the threshold for substantial meaningful change in the elderly. 80% of the open shunt group exceeded that threshold compared to only 24% of the placebo group.
The Tenet scale, which measures gait imbalance, also showed significant improvement in the open shunt group. However, screening measures for good condition using the MoCA scale and bladder symptoms did not reach significance at three months, though tertiary outcomes for cognitive testing, quality of life and functional independence tended in favor of shunting. Importantly, falls were more common in the placebo group at 46% compared to 25% in the open shunt group. This is a meaningful safety signal given how dangerous falls are in older adults. There were also real risks with active shunting. Subdural hematomas occurred in 12% of the open shunt group versus 2% of placebo and three even required surgical intervention. Positional headaches from low CSF pressure were more common in the open shunt group at 59% versus 28%. The good news is that the adjustable valve allowed non-invasive management of many of these complications. While this trial gives us reasons to be cautiously optimistic about shunting for appropriately selected iNPH patients, it's worth noting that we only have evidence for improvement in gait and follow-up is only three months.
Longer-term data is still being collected so we don't know yet how durable these benefits are. If you want to read more, please find the paper by Mark G. Luciano, et al. It's titled A Randomized Trial of Shunting for Idiopathic Normal Pressure Hydrocephalus published in the New England Journal of Medicine in December 2025. That's your neurology menu for today. Keep exploring and we'll see you next time.
- Visa fler
