Headache Medicine and Women's Health Series: Menstrual Migraine

In part one of this two-part series, Dr. Neishay Ayub discusses the history of a novel anti-epileptic drug, levetiracetam.  Show citations:  Abou-Khalil B. Levetiracetam in the treatment of epilepsy. Neuropsychiatr Dis Treat. 2008;4(3):507-523. doi:10.2147/ndt.s2937  Löscher W, Gillard M, Sands ZA, Kaminski RM, Klitgaard H. Synaptic Vesicle Glycoprotein 2A Ligands in the Treatment of Epilepsy and Beyond. CNS Drugs. 2016;30(11):1055-1077. doi:10.1007/s40263-016-0384-x Rogawski MA. Brivaracetam: a rational drug discovery success story. Br J Pharmacol. 2008;154(8):1555-1557. doi:10.1038/bjp.2008.221 Ulloa CM, Towfigh A, Safdieh J. Review of levetiracetam, with a focus on the extended release formulation, as adjuvant therapy in controlling partial-onset seizures. Neuropsychiatr Dis Treat. 2009;5:467-476. doi:10.2147/ndt.s4844 Wu PP, Cao BR, Tian FY, Gao ZB. Development of SV2A Ligands for Epilepsy Treatment: A Review of Levetiracetam, Brivaracetam, and Padsevonil. Neurosci Bull. 2024;40(5):594-608. doi:10.1007/s12264-023-01138-2 Mahmoud A, Tabassum S, Al Enazi S, et al. Amelioration of Levetiracetam-Induced Behavioral Side Effects by Pyridoxine. A Randomized Double Blind Controlled Study. Pediatr Neurol. 2021;119:15-21. doi:10.1016/j.pediatrneurol.2021.02.010 Major P, Greenberg E, Khan A, Thiele EA. Pyridoxine supplementation for the treatment of levetiracetam-induced behavior side effects in children: preliminary results. Epilepsy Behav. 2008;13(3):557-559. doi:10.1016/j.yebeh.2008.07.004 Romoli M, Perucca E, Sen A. Pyridoxine supplementation for levetiracetam-related neuropsychiatric adverse events: A systematic review. Epilepsy Behav. 2020;103(Pt A):106861. doi:10.1016/j.yebeh.2019.106861 Show transcript:  Dr. Neishay Ayub: Hello, my name is Neishay Ayub, and today we are discussing the history of a novel anti-epileptic drug, levetiracetam. It's a story of a scientific dead end, a radical new testing method, and a mystery that took years to unravel. To set the scene, let's go back to 1974. The pharmaceutical company, UCB Pharma, was working on compounds to boost cognitive function. They were looking for a successor to their drug piracetam. During this research, levetiracetam was first synthesized, but the compound didn't show any significant brain-boosting effects. With no discernible purpose, it was filed away and largely forgotten. For nearly two decades, this medicine sat on a shelf an anonymous entry in a long list of failed drug candidates. The story could have ended there, but in the early 1990s, researchers took a different approach to drug discovery. Researchers screened their entire library of forgotten compounds against audiogenic seizure-susceptible mice. These are mice prone to seizures triggered by sound. Levetiracetam was incredibly ineffective in chronic epileptic mice. Interestingly, levetiracetam had previously failed traditional screening tests which was to prevent acute seizures in normal animals subjected to maximal electroshock or pentylenetetrazole. Levetiracetam was pushed forward to human clinical trials and was found to be efficacious in three placebo-controlled, randomized, blinded clinical trials for adults with refractory focal epilepsy. Two of the clinical trials reviewed levetiracetam three grams per day compared to placebo. They found the responder rate, i.e., 50% reduction in seizure frequency, was 39% to 42% for patients on three grams per day versus placebo at 10% to 16% when used as adjunctive therapy. One of these trials also used levetiracetam as monotherapy, noting a median percent reduction in focal seizure frequency of 73%, a responder rate of 59%, and 18% of patients achieving seizure freedom. In November 1999, the FDA gave its approval for adjunctive treatment of partial onset seizures. While levetiracetam was effective, how it worked was still unclear. It didn't affect the ion channels and neurotransmitter receptors that older, more traditional anti-epileptic drugs targeted. Eventually in 2004, scientists made another breakthrough. They identified the drug's primary molecular target, a protein called SV2A. This protein is involved in regulating the release of neurotransmitters. Instead of suppressing all neurologic activity, levetiracetam appears to bind to SV2A and selectively modulate neurotransmitter release in overactive seizing neurons. This precise mechanism is why it has such a favorable side effect profile. With the mystery solved and a novel mechanism understood, levetiracetam continues to be a popular anti-seizure medication to this day, and its use has been expanded. Further clinical trials led to FDA approvals for use in adult and pediatric patients with myoclonic epilepsy for myoclonic seizures as well as adult and pediatric patients with idiopathic generalized epilepsy for primary generalized tonic-clonic seizures. There is an off-label use for status epilepticus and seizure prophylaxis in TBI, in traumatic brain injury, subarachnoid hemorrhage, and neurosurgical cases. Formulations have also expanded to include tablets and liquid formulations for immediate release, extended-release tablets, and intravenous formulations. Today, with the original patent expired, generic versions are available, making this treatment accessible to millions. The journey of levetiracetam from an abandoned compound to a frontline treatment is a powerful reminder that in science, a failure might just be a success waiting to be tested in a different way.

Dr. Tesha Monteith discusses menstrual migraine and treatment options.  Show transcript: Dr. Tesha Monteith: This is Tesha Monteith with the Neurology Minute. Welcome back to our series on headache medicine and women's health. I'm continuing our discussion on menstrual migraine, and I want to focus on treatment. We talked about increasing the yield of diagnosis for menstrual migraine, but what are the best ways to treat our patients? I think there are two broad categories we can think about: We can think about non-hormonal methods or hormonal methods. The non-hormonal methods include a combination of abortive therapies, as well as preventative therapies that can be used for a mini prophylaxis, as well as when patients have a higher burden of overall migraine, considering the general highly effective preventive therapies. Common mini prophylaxis include triptans such as Frovatriptan, Naratriptan, and Zolmitriptan when used twice per day. Nonsteroidal anti-inflammatories can be used for five to seven days around menses, such as naproxen, 550 milligrams twice per day. Magnesium, 360 milligrams daily or higher, can also be started mid-cycle, so day 15, towards menstruation. Although considered off-label, gepants, ubrogepant, as well as rimegepant, can also be used during the susceptible window. This is Tesha Monteith. Thank you for listening to the Neurology Minute. 

In the January episode of the President's Spotlight, Dr. Jason Crowell and Dr. Natalia Rost discuss AAN's plans for 2026, including a general neurology boot camp, Autoimmune Conference, and new resources for members.  Stay informed by watching the President's Spotlight video.  Show transcript: Dr. Jason Crowell: Hello, and welcome to today's Neurology Minute. This is the first installment of 2026 that we have with the president of the AAN, Natalia Rost. Natalia, thanks so much for joining us today, we look forward to our monthly chats to talk about things going on with the AAN. Before we start talking about the plans for 2026 with the American Academy of Neurology, what are the things that are on your mind? Dr. Natalia Rost: Happy new year, Jason, great to join you today. Well, first of all, I think 2026 is going to be a strong year, and as I think what's coming down our pipeline, it's our work to promote brain health and to support neuroscience research. It's the fight that we have to fulfill Medicare payments, and to protect patient access to care. Our efforts to advance physician-led neurology teams and to reduce burnout. And to always stand firmly for science and evidence-based medicine. Dr. Jason Crowell: Now, I know every year the AAN has new programming and content that they're putting out, what's going to be in store for 2026? Dr. Natalia Rost: First of all, we're launching a brand new general neurology bootcamp at the annual meeting, high impact learning, real connections, and great energy guaranteed. Also back by popular demand, the Autoimmune Conference will take place again this summer, featuring all the latest science, so I'm excited about that. For our advanced practice provider members, expect a new online toolkit to improve your neurology knowledge and patient care skills. For our residents, we are adding a new pediatric neurology option for our RITE exam lineup. And last but not least, we are fully reimagining our patient education on brainandlife.org, because as you know and as our members know, an informed public makes powerful partners in our Brain Health For All movement. Dr. Jason Crowell: Terrific. And so, are there any efforts from last year that will continue to be a focus for this coming year? Dr. Natalia Rost: Two things immediately come to mind, and our work will only grow stronger there. Number one is to continue to modernize our digital platforms and provide resources to our members to tackle AI and emerging technologies. As you know, this is a big issue. And number two is to advocate relentlessly for fair reimbursement and access to care. Our advocacy is only going to grow stronger in 2026. Dr. Jason Crowell: So, Natalia, most of us are still working to keep our New Year's resolutions intact, I'm a few days into my exercise program, we'll see how long that goes. But what would you say are the New Year's resolutions, if you will, for the AAN? Dr. Natalia Rost: Well, this year is going to be the year to fully embrace our Brain Health For All approach, I think. Neurologists are the experts in brain health, so our promise is for the AAN to continue tirelessly support our members so they can lead, care, and thrive as they do. Dr. Jason Crowell: Terrific, Natalia. Thanks so much. Happy New Year again. Dr. Natalia Rost: Happy New Year.    

Dr. Derek Stitt and Drs. Joseph Safdieh and Matthew S. Robbins discuss subspecialization's impact on patient care, why preserving a core neurologist identity matters, and how training can reinforce it. Show citation: Safdieh JE, Robbins MS. Opinion & Special Articles: The Core Identity of the Neurologist. Neurology. 2025;105(9):e214265. doi:10.1212/WNL.0000000000214265 

Dr. Shuvro Roy and Dr. Rosa Cortese discuss new ways to improve MS and MOGAD diagnosis, including how AI and imaging could enhance accuracy and influence future care. Show citations: Cortese R, Sforazzini F, Gentile G, et al. Deep Learning Modeling to Differentiate Multiple Sclerosis From MOG Antibody-Associated Disease. Neurology. 2025;105(6):e214075. doi:10.1212/WNL.0000000000214075 

Dr. Bradley Ong discusses evidence for candesartan in migraine prevention. Show citation: Øie LR, Wergeland T, Salvesen Ø, et al. Candesartan versus placebo for migraine prevention in patients with episodic migraine: a randomised, triple-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2025;24(10):817-827. doi:10.1016/S1474-4422(25)00269-8

In the second part of this two-part series, Dr. Shuvro Roy examines the study's findings and their implications for clinical practice moving forward. Show citation: Kim M, Park YH, Song YS, et al. Gait Improvement Following CSF Tap Test in NPH Patients With and Without Striatal Dopaminergic Deficit: A Preliminary Study. Neurol Clin Pract. 2025;15(6):e200549. doi:10.1212/CPJ.0000000000200549

In part one of this two-part series, Dr. Shuvro Roy explains idiopathic normal pressure hydrocephalus (iNPH), its diagnostic challenges, and a study on whether dopamine transporter (DAT) scan results affect gait improvement after a CSF tap test. Show citation: Kim M, Park YH, Song YS, et al. Gait Improvement Following CSF Tap Test in NPH Patients With and Without Striatal Dopaminergic Deficit: A Preliminary Study. Neurol Clin Pract. 2025;15(6):e200549. doi:10.1212/CPJ.0000000000200549

Drs. Mahinda Yogarajah, Benjamin Tolchin, and Jon Stone discuss recommendations for clinicians, patients, and other stakeholders on the management of functional seizures.  Show citation: Tolchin B, Goldstein LH, Reuber M, et al. Management of Functional Seizures Practice Guideline Executive Summary: Report of the AAN Guidelines Subcommittee. Neurology. 2026;106(1):e214466. doi:10.1212/WNL.0000000000214466  Show transcript:  Dr. Mahinda Yogarajah: Welcome to this edition of Neurology Minute. I'm your host for this. My name's Mahinda Yogarajah. I've just finished interviewing Dr. Ben Tolchin and Jon Stone for this week's Neurology® Podcast. For today's Neurology Minute, I'm hoping Ben can tell us the main points of the podcast and the paper discussed in that podcast. Dr. Ben Tolchin: We discussed the AAN guideline on the Management of Functional Seizures. This is the first American Academy of Neurology evidence-based guideline on functional neurologic disorder. It includes a systematic review of the randomized controlled trials relating to the treatment of this disorder, which found that psychological interventions are possibly effective in improving the chance of achieving freedom from functional seizures, in reducing the frequency of functional seizures, in improving quality of life, and in improving anxiety. In addition to the systematic review, there are clinical recommendations based on the systematic review and on related evidence. The recommendations deal with all stages of the diagnosis, management, and treatment of functional seizures and are particularly relevant to neurologists caring for patients with functional seizures. In addition, there are recommendations for future research relating to the diagnosis and management of functional seizures. Dr. Mahinda Yogarajah: Thank you, Ben. For more information, I'd recommend go to the main podcast or go and have a read of the article that's been published in Neurology® on the Management of Functional Seizures Practice Guidelines.

Drs. Greg Cooper, Natalia Rost, and Behnam Sabayan discuss preventive neurology and the need for neurologists to move beyond diagnosis and treatment toward proactive strategies for brain health.  Show citation: Sabayan B, Boden-Albala B, Rost NS. An Ounce of Prevention: The Growing Need for Preventive Neurologists. Neurology. 2025;105(1):e213785. doi:10.1212/WNL.0000000000213785 Show transcript:  Dr. Greg Cooper: Hi, this is Greg Cooper. I just finished interviewing Behnam Sabayan and Natalia Rost for this week's Neurology® Podcast. For today's Neurology Minute, I'm hoping you can tell us the main points of your paper, An Ounce of Prevention, the Growing Need for Preventative Neurologist. Dr. Behnam Sabayan: We are living in a very exciting time for the field of neurology where we are not just getting very good at diagnosis and treatment of neurological condition, but also we are stepping one step back, and that means that we will find the root causes of neurological conditions. We would act as preventive specialists and we would decrease the burden of neurological conditions, not just at the individual level, but also at the population level. And this paper calls for thinking about playing roles at different levels and stages from our offices and our rounds all the way to the community to be brain health advocates and helping other fields and disciplines to reduce the burden of neurological conditions. Dr. Greg Cooper: Well, thank you for that summary and for all of your work on this topic. Please check out this week's podcast to hear the full interview or read the full article published in Neurology®, An Ounce of Prevention: The Growing Need for Preventative Neurologists. Thank you.