Neurology Minute

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. 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.

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.

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 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.