Seizures and Epilepsy in Patients With Untreated Cerebral Cavernous Malformations

Dr. Halley Alexander and Dr. Abel Sandmann discuss seizure rates and risk factors in patients with cerebral cavernous malformations (CCMs) during long-term follow-up without CCM intervention.  Show citation:  Sandmann ACA, Vandertop WP, White PM, Verbaan D, Coutinho JM, Al-Shahi Salman R. Seizures and Epilepsy in Patients With Untreated Cerebral Cavernous Malformations: A Prospective, Population-Based Cohort Study. Neurology. 2025;105(11):e214387. doi:10.1212/WNL.0000000000214387  Show transcript:  Dr. Halley Alexander: Hi, this is Halley Alexander with today's Neurology Minute. I'm here with Abel Sandmann from Amsterdam University Medical Center, and we just finished recording a full-length podcast about some exciting findings related to cerebral cavernous malformations and the risk of seizures and epilepsy. Abel, can you give our listeners a rundown of the most exciting findings and how it can change practice? Dr. Abel Sandmann:  In our paper, we show that patients with a cerebral cavernous malformation who have a first unprovoked seizure should be diagnosed with epilepsy and considered for anti-seizure medication, as most of them achieve long-term seizure freedom with medical therapy alone. These findings are based on a prospective population-based cohort study in which we analyze long-term follow-up and assess the rates and risk factors for: one, a first-ever epileptic seizure; two, seizure recurrence to evaluate the updated ILAE definition of epilepsy; and three, seizure freedom over two years and five years among patients with epilepsy. We found that among patients who had never experienced a seizure before, the 10-year risk of a first-ever seizure was only 6%. This supports current recommendations against prophylactic anti-seizure medication in patients who are incidentally diagnosed with a cerebral cavernous malformation. However, following a first unprovoked seizure, the 10-year risk of recurrence was 80%, which exceeds the 60% threshold defined by the ILAE. This justifies diagnosing epilepsy after the first and provoked seizure in this population. Given that the risk of recurrence was lower in patients treated with anti-seizure medication after the first seizure, this supports early initiation of therapy, although these treatment analyses were non-randomized and should be interpreted cautiously. Most patients who met the definition of epilepsy became two year and five years seizure-free with medical management alone. But some patients with cerebral cavernous malformations develop medically intractable seizures and might benefit from surgical treatments. Dr. Halley Alexander: Excellent. Thank you so much, Abel. You can find the full-length podcast, which is available now on the Neurology Podcast, or you can also find the full article in Neurology at neurology.org, or in the December 2025 print issue. As always, thanks for tuning in for today's Neurology Minute.   

In part one of this series, Dr. Tesha Monteith and Dr. Jennifer Robblee discuss an international consensus definition for refractory migraine and why clearer criteria are needed.  Show citations: Robblee J, Minen MT, Friedman BW, Cortel-LeBlanc MA, Cortel-LeBlanc A, Orr SL. 2025 Guideline Update to Acute Treatment of Migraine for Adults in the Emergency Department: The American Headache Society Evidence Assessment of Parenteral Pharmacotherapies. Headache. 2026;66(1):53-76. doi:10.1111/head.70016 Robblee J, Khan FA, Marmura MJ, et al. Reaching International Consensus on the Definition of Refractory Migraine Using the Delphi Method. Cephalalgia. 2025;45(9):3331024251367767. doi:10.1177/03331024251367767 Show transcript:  Dr. Tesha Monteith: Hi, this is Tesha Monteith with the Neurology Minute. I've just been speaking with Jennifer Robblee about her exciting work defining refractory migraine with an international consensus, as well as her work with the American Headache Society on a guideline update for parental pharmacotherapies for migraine in the emergency department. Hi, Jennifer. Thanks again for coming on our Neurology Minute. Dr. Jennifer Robblee: Thank you so much for having me. I'm delighted to be here. Dr. Tesha Monteith: You've done a lot of work in the area of refractory migraine. Why don't you tell us why you felt there need to be clarification on the definition? Dr. Jennifer Robblee: Well, this is a patient population that I'm really passionate about. There's not enough research out there. We don't really know who these patients are, why they're not responding to treatment, and we don't know how to help them because we have no guidelines, obviously, since they're refractory to what we use for treating. So I thought it was really good to get an international group to standardize our definition and hopefully help move the research forward. Dr. Tesha Monteith: Why don't you tell us a little bit about the consensus definition Dr. Jennifer Robblee: So we came up with an international consensus definition for refractory migraine that was laid out the same way that migraine is, say, laid out in the ICHD-3 diagnostic manual, if you want to call it that. So we have different criteria on. So criterion A basically allowed for it to be episodic or chronic migraine. Criterion B had three subcriteria, so you needed to have at least two out of three of severe to very severe disability and/or a constant background headache and/or at least eight monthly migraine days. Criterion C was about the lack of response to treatment. And basically it says that you needed to have failure of all medication categories, and there is an extra one for an other in case any new treatments emerge before the diagnostic criteria get updated. And what we considered a, quote, unquote, failure was that you did not have a 50% improvement in monthly migraine days, or you had intolerable side effects, or you had an absolute contraindication. There is a caveat that you need to have at least four true lack of efficacies. And then the CGRP monoclonal antibody or gepant category and the onabotulinumtoxin toxin category both had to be a true lack of response. And of course, there's a criterion B to say that this should not be from another diagnosis. Dr. Tesha Monteith: Thanks so much, Jennifer.

Dr. Stacey Clardy reviews biotin deficiency and biotin-related lab interference. Show transcript:  Dr. Stacey Clardy: Hi, this is Stacey Clardy from the Salt Lake City VA and the University of Utah, and I'm back with you for another lab minute. Today, let's talk about Biotin or vitamin B7, because the Biotin story in neurology has two very different aspects. The first is a real deficiency, which is uncommon, but clinically really important. And the second is the modern problem of biotin supplementation that's quietly wrecking our lab interpretation. So first, true biotin deficiency in adults is less common, but it can look like a multi-system neurologic syndrome. The classic teaching is dermatitis and alopecia, so keep those in your mind. But neurologists end up seeing the downstream features. So lethargy, depression, paresthesias and sometimes ataxia. Now, in infants and children, the bigger higher stakes entity is biotinidase deficiency, which is fortunately screened in many newborn programs in the US. Untreated, it can produce seizures, developmental delay, optic atrophy, and hearing loss. And the key point is that these neurologic injuries can be prevented if biotin is started early enough. Also, remember, there are numerous reports now in the literature of it mimicking the clinical and radiological features of neuromyelitis optica spectrum disorder or multiple sclerosis. So if you have one of those diagnoses and you're not quite sure that it's right, keep biotinidase deficiency in the back of your mind. Now, what most of us clinicians are living with is the biotin supplement era. So high dose biotin, taken by a lot of people, either knowingly or unknowingly, can interfere with biotin streptavidin immunoassay platforms. And the direction of error depends on the assay design, but the practical pitfalls are simple. You can be handed a lab pattern that screams something like hyperthyroidism or other endocrine pathology, and it can actually be purely analytical artifact. Thyroid testing is the most common example, and troponin and other assays can also be affected depending on the assay platform. So a common clinical misstep is to treat the lab burnout rather than the patient. So if your patient symptoms don't match this new endocrine emergency that the lab appears to be showing, ask, are they taking biotin? This is commonly in hair and nail supplements or buried in the myriad ingredients of another fix all supplement. So you need to find out if it's in any of those. The easiest thing is to say, tell me all of the supplements and the brands you're taking. And then I usually do a quick internet search right there to find out if biotin's in there. And so the lowest friction fix is generally to repeat the test after holding biotin for an appropriate interval. At least a week is usually a safe time to guess about. The key is coordination with the laboratory. Not every lab behaves the same and some systems now actually have evolved mitigations, which is quite helpful. So that's the biotin update. So remember, biotin deficiency is treatable and sometimes urgent. And also, biotin supplementation is now a common lab confounder that can trigger avoidable diagnostic and therapeutic errors. Thanks for spending a few minutes with me. This is Stacey Clardy, and that's your lab minute.  

In this episode, Dr. Stacey Clardy reviews the March 9 Capitol Hill Report, recapping key takeaways from Neurology on the Hill. Stay updated with what's happening on the hill by visiting aan.com/chr.  Learn how you can get involved with AAN advocacy.  Show transcript:  Dr. Stacey Clardy: Hi, this is Stacey Clardy with today's Neurology Minute. It's an advocacy update from the AAN's Capitol Hill Report. More than 200 AAN members came to Washington, DC, last week for the AAN's annual advocacy fly-in, Neurology on the Hill. As you probably know, this is the annual chance for neurologists to get some face-to-face time with members of Congress or their aides in the US right on Capitol Hill. AAN members had three asks for this year's event. We did cover them last week individually on the Neurology Minute, so have a listen if you want more detail, but I'll review them quickly.  First, we asked for a permanent inflationary update to physician reimbursement based on the Medicare Economic Index and to raise the outdated budget neutrality triggers in the Medicare physician fee schedule. Under the current system, the AAN needs to ask Congress nearly every year to fix a proposed cut to physician payment under Medicare, so it's time for a better solution. The second ask, AAN members requested their legislators to co-sponsor the Connect for Health Act in the US. This legislation would support patient access to care by making those old COVID era telehealth flexibilities now permanent rather than requiring repeated extensions. And the need to make these flexibilities permanent was especially clear in the US during the 2025 government shutdown when Medicare recipients' access to telehealth lapsed for about 45 days. And finally, the third ask was for the BRAIN Initiative at the National Institutes of Health, it's a very important program funding basic research into the brain and it's losing a key funding stream that was previously provided through the 21st Century Cures Act, so the AAN members asked their legislators to close the gap by supporting $468 million in funding for the BRAIN Initiative in 2027. If you didn't go to Neurology on the Hill but want to support these causes, check the AAN's Advocacy Action Center, and you could contact your representative that way. Outside of DC news, a number of state legislators are considering bills that positively or negatively affect neurology. The AAN has weighed in on several of those bills with advocacy letters. The bills it supported include later school start times in Pennsylvania, restricting AI prior authorization denials in Florida and Hawaii, mandating coverage for telehealth services in Massachusetts, and reducing prior authorization burdens in Arizona and Kansas. The AAN opposed a New York bill, however, that would give chiropractors the ability to evaluate and diagnose neuromusculoskeletal conditions and provide consultation advice and recommendations on neurology. So you can find links and more in the Capitol Hill Report. It's available on aan.com/CHR, that's short for Capitol Hill Report, and in US members' email inboxes. That's it for this time. Thanks. I'm Stacey Clardy for The Minute. 

In this episode, Dr. Stacey Clardy reviews the February 23rd Capitol Hill Report, recapping key takeaways from Neurology on the Hill. Stay updated with what's happening on the hill by visiting aan.com/chr.  Learn how you can get involved with AAN advocacy.  Show transcript:  Dr. Stacey Clardy: Hi, this is Stacey Clardy with today's Neurology Minute. It's an advocacy update from the AAN's Capitol Hill Report. More than 200 AAN members came to Washington, DC, last week for the AAN's annual advocacy fly-in, Neurology on the Hill. As you probably know, this is the annual chance for neurologists to get some face-to-face time with members of Congress or their aides in the US right on Capitol Hill. AAN members had three asks for this year's event. We did cover them last week individually on the Neurology Minute, so have a listen if you want more detail, but I'll review them quickly.  First, we asked for a permanent inflationary update to physician reimbursement based on the Medicare Economic Index and to raise the outdated budget neutrality triggers in the Medicare physician fee schedule. Under the current system, the AAN needs to ask Congress nearly every year to fix a proposed cut to physician payment under Medicare, so it's time for a better solution. The second ask, AAN members requested their legislators to co-sponsor the Connect for Health Act in the US. This legislation would support patient access to care by making those old COVID era telehealth flexibilities now permanent rather than requiring repeated extensions. And the need to make these flexibilities permanent was especially clear in the US during the 2025 government shutdown when Medicare recipients' access to telehealth lapsed for about 45 days. And finally, the third ask was for the BRAIN Initiative at the National Institutes of Health, it's a very important program funding basic research into the brain and it's losing a key funding stream that was previously provided through the 21st Century Cures Act, so the AAN members asked their legislators to close the gap by supporting $468 million in funding for the BRAIN Initiative in 2027. If you didn't go to Neurology on the Hill but want to support these causes, check the AAN's Advocacy Action Center, and you could contact your representative that way. Outside of DC news, a number of state legislators are considering bills that positively or negatively affect neurology. The AAN has weighed in on several of those bills with advocacy letters. The bills it supported include later school start times in Pennsylvania, restricting AI prior authorization denials in Florida and Hawaii, mandating coverage for telehealth services in Massachusetts, and reducing prior authorization burdens in Arizona and Kansas. The AAN opposed a New York bill, however, that would give chiropractors the ability to evaluate and diagnose neuromusculoskeletal conditions and provide consultation advice and recommendations on neurology. So you can find links and more in the Capitol Hill Report. It's available on aan.com/CHR, that's short for Capitol Hill Report, and in US members' email inboxes. That's it for this time. Thanks. I'm Stacey Clardy for The Minute. 

In the March episode of the President's Spotlight, Dr. Jason Crowell and Dr. Natalia Rost share key updates and strategic insights for the upcoming April meeting in Chicago.  Stay informed by watching the President's Spotlight video.   Show transcript:  Dr. Jason Crowell: Hey, this is Jason Crowell. Thanks for listening to today's Neurology Minute. Once again, this month, we have Natalia Rost joining us, the president of the AAN for her presidential spotlight. Natalia, the sun is starting to come out. The flowers are starting to bloom. Spring is here. What is going on with the academy? What would you like to tell us about this month? Dr. Natalia Rost: These are exciting times indeed. Our annual meeting is just one month away. And so I'm looking forward to all of us coming together to learn, share ideas, and to connect. And this year, the world's largest neurology event is even larger. And I like to say it's my meeting of 15,000 friends. Dr. Jason Crowell: Terrific. For those who are listening today who haven't heard about the annual meeting, what would you like for them to know about it? Dr. Natalia Rost: Well, so the meeting takes place April 18th through 22nd in Chicago and online. And like so many, I love Chicago. It's a world-class city. It's a major travel hub and making it easy for many of us to attend. And we're expecting presentations of more than 3,500 abstracts. It's a new record for our meeting. Registration is also trending ahead of previous years, so now is the time to make your plans. Dr. Jason Crowell: And what would you say are the three things that you look forward to the most every year at the meeting? Dr. Natalia Rost: Well, first of all, the Sunday of this meeting, April 19th, is our research day, which will focus on advancing neuroscience and the AAN's renewed commitment to research funding we talked about last month. It includes my presidential plenary, which is titled Neuroscience at the Crossroads, and which will feature interactive panels of seasoned neuroscience leaders and clinician scientists who are right in the midst of their exciting careers. We will have our research hub to take part in many opportunities to support our high quality research program, so that's going to be great. Another highlight is a celebration of the extraordinary accomplishments of Dr. Walter Koroshetz, the immediate past NINDS director, and a phenomenal neurologist who is our 2026 President's Award winner and who will join us at the Presidential Plenary. This is going to be a very special and spirited event. And also, I'm excited to debut the new Brain Hub this year. I hope folks will stop by. Along with that, we have a special museum exhibit and reception for the Neurology Journal's 75th anniversary. I sure will be stopping by both. Dr. Jason Crowell: I would say that people in the world of medicine often misunderestimate just how much fun neurologists can be. What fun is planned for the annual meeting this year? Dr. Natalia Rost: Oh yeah, we're on it. As always, we will have our celebrated annual meeting party on Sunday night. This year, the entire Griffin Museum of Science and Industry will be hours to explore while you enjoy your food, drinks, and conversation with colleagues. Dr. Jason Crowell: And for our listeners, where can they learn more about the annual meeting and all the details? Dr. Natalia Rost: Please register now at aan.com/am. This is an annual meeting you won't want to miss, so join me with everything neurology premier event has to offer. Dr. Jason Crowell: Terrific. Natalia, thanks so much. Looking forward to Chicago.  

Dr. Tesha Monteith and Dr. Patricia Pozo-Rosich discuss the latest advancements in headache medicine, focusing on key research findings from 2025.  Show transcript: Dr. Tesha Monteith: Hi, this is Tesha Monteith with the Neurology Minute. Welcome to our 2026 Headache Medicine Series. I've just been speaking with Patricia Pozo-Rosich about all of the exciting advances in headache medicine in 2025. For a minute, why don't you summarize some of the key advances in headache medicine research? Dr. Patricia Pozo-Rosich: I think that we have good news in headache. We are currently phase two trials for two or three different compounds, anti-part two, packup and new toxins. So we are actually, I think, excited to find out the phase 2B trial results and phase three. So well, that's something that I think is worth mentioning. Then I think it is important to remember that we have new data coming from real world evidence with long-term use of anti CGRP therapies. We also have data that shows that anti CGRP therapies are useful for patients with migraine and major depressive disorder, as well as as children. Finally, I think that it is very important to remind everyone that there are new papers on practice recommendations around the world on how we have to treat our patients with migraine, and that is related both to the acute and preventive therapies. And finally, couple of position statements that have been written by the International Hague Society that strive to improve the quality of how migraine individuals are treated, and that really conveys a paradigm shift where we probably should be starting preventive therapy sooner than later. Dr. Tesha Monteith: Great. Thank you so much for that quick summary. And please check out the Full Headache Medicine series. I appreciate talking to you, Patricia, and look forward to discussing more highlights next time. Dr. Patricia Pozo-Rosich: Thank you, Tisha. See you very soon. Dr. Tesha Monteith: And thank you for listening to the Neurology Minutes.

In part two of the series, Dr. Andy Southerland and Dr. Seemant Chaturvedi break down key takeaways from the OCEANIC‑STROKE trial.  Show citation:  Read more about the OCEANIC-STROKE trial.  Show transcript:  Dr. Andy Southerland:  Hello everyone. This is Andy Southerland from the University of Virginia. For today's Neurology Minute, I've just been speaking with my colleague, Seemant Chaturvedi from the University of Maryland, about exciting trials presented at this year's 2026 International Stroke Conference from the American Heart Association, American Stroke Association. And the one we want to discuss for today's Neurology Minute in brief was the OCEANIC-STROKE trial. This was a very large international trial looking at the use of a novel antithrombotic agent, a Factor XI inhibitor, compared to placebo as an adjunct to our traditional antiplatelet therapies for secondary stroke prevention. And it was received with quite a bit of excitement. So Seemant, tell us in brief, what did we learn from OCEANIC-STROKE? Dr. Seemant Chaturvedi:  One new class of agents, which is being tested are the Factor XIa inhibitors. And this has a unique mechanism of action, and it's believed that it can reduce thrombotic events without causing an increase in bleeding, which would be truly a major breakthrough. And so in OCEANIC-STROKE, over 12,000 patients were enrolled with either stroke or high-risk TIA within 72 hours of the last event. And the trial found that patients who had fairly mild strokes with a median NIH score of two, that when you add the asundexian 50 milligrams per day on top of either dual antiplatelet or single antiplatelet therapy, that there was an improved outcome and reduction in stroke with asundexian. There was a 2.2% absolute reduction in ischemic stroke, 26% in relative terms. Stroke, MI, and vascular death was also reduced with asundexian, as was disabling stroke. An exciting finding was that major bleeding was not increased with asundexian. And so this confirmed the preclinical hypothesis. And so I think this was a significant result in terms of reducing recurrent ischemic stroke without increasing bleeding. And so I think we eagerly await the full publication, and I think it could be applicable to many of the patients that we see in our clinical practice. Dr. Andy Southerland:  So asundexian, folks, you'll hear more about this as the drug hopefully comes on the market and we see the full primary publication of this OCEANIC-STROKE trial, but exciting nonetheless to have a possible new treatment to help us reduce the risk of recurrent stroke for our patients. So Seemant, thanks so much again for joining us for today's Neurology Minute. And I encourage all of our listeners, as always, to listen to the full podcast interview ain The Neurology Podcast. Seemant, thanks for joining us. Dr. Seemant Chaturvedi:  My pleasure.  

In part one of this series, Dr. Andy Southerland and Dr. Seemant Chaturvedi discuss two trials highlighted at the 2026 International Stroke Conference.  Show citation:  Read more about the CHOICE-2 trial.  Show transcript:  Dr. Andy Southerland: Hello everyone. This is Andy Southerland. And for this week's Neurology Minute, I have just been speaking once again with my colleague, Seemant Chaturvedi, about his impressions from this year's 2026 American Heart Association, American Stroke Association International Stroke Conference. We've discussed a number of the very exciting pivotal trials presented at this year's meeting that occurred just a couple of weeks ago. But for the minute today, we want to just highlight two that were represented as late breaking trials in the world of acute stroke treatment. And the first was OPTION, which was a trial looking at extended window thrombolysis patients between four and a half and 24 hours. And the second was in the use of thrombolysis as an adjunct local treatment in patients receiving thrombectomy. So Seemant, to the best of your ability in our brief snippet today, what were the main highlights from these studies? Dr. Seemant Chaturvedi: In the OPTION trial, 570 patients were enrolled from China, and these were patients in the four and a half to 24 hour window with no evidence of large vessel occlusion. And they had a mismatch present at baseline imaging, median NIH score was seven. And when the tenecteplase was administered in this select group of patients, there was improvement in the excellent outcome of about 44% with tenecteplase and 34% with placebo. And there was a slight increase in hemorrhage of about 3%, but no increase in mortality. The second trial, CHOICE-2, also looked at thrombolysis, but it looked at local intraarterial thrombolysis following thrombectomy. And they enrolled patients with a median NIH score of 15 and the patients were enrolled from Spain and they gave a local TPA versus placebo following successful thrombectomy. And they also reported improved outcomes with about 57.5 having an excellent outcome with intraarterial TPA compared to 43% with placebo. There was slightly increased mortality in the TPA group, but this didn't seem to be explained by intracerebral hemorrhage. And so I think both of these were very intriguing and they add some complexity to acute stroke treatment. And so primary stroke centers and comprehensive stroke centers need to discuss the results with their teams and see if they want to embrace these treatment options. Dr. Andy Southerland: Fantastic, Seemant. So bottom line is thrombolysis is much more than it used to be in that very narrow time window and that very narrow indication. There are now patients who may benefit in that extended time window, and it's also being shown to have benefit in cases in which we get incomplete reperfusion with our traditional mechanical thrombectomy. So take that and run with it. Hopefully we can apply it to our stroke systems of care and help patients. Thank you again, Seemant for being with us on today's Neurology Minute. Seek out the full interview and also the primary publications as well.  

In part four of this series, Dr. Tesha Monteith explores the true potential of AI integration in medical education.  Show transcript:  Dr. Tesha Monteith: Hi. This is Tesha Monteith with the Neurology Minute. I've been speaking with Roy Strowd, Jeff Ratliff, and Justin Abbatemarco about the use of AI in neurology education for the neurology podcast. My take is that we're just getting started with this stuff, including the true potential of AI integration in medical education. In my regular work, I used AI to generate clinical case vignettes that help trainees practice diagnostic reasoning, and also to create patient images that better reflect the cultural diversity of our neurology population. Beyond content creation, AI has helped me evaluate my curriculum by identifying gaps and strengths to better train fellows and residents. I've even used it as a tool to help me frame feedback, highlighting strengths, identifying areas for growth, and to provide a more forward-looking feedback approach. AI still needs work. It should be monitored and scrutinized, and it certainly can't replace us, but it can provide meaningful augmentation of how we teach and how our learners develop. This is Tesha Monteith. Thank you for listening to the Neurology Minute.