Resistance to epilepsy treatments may wane over time

(Press-News.org) About one-third of patients with focal epilepsy, a common form of the neurological disorder, are believed to respond poorly to available therapies. Yet they too may eventually see improvement, if not total relief, from their seizures, a new study shows. 

Most people with epilepsy have focal epilepsy, which occurs when nerve cells in a certain brain region send out a sudden, excessive burst of electrical signals. This uncontrolled activity, which is called a focal seizure, can cause problems such as abnormal emotions or feelings and unusual behaviors. 

Led by NYU Langone Health researchers, the new study, which was part of the international Human Epilepsy Project, explored the minority of focal epilepsy patients who are considered treatment resistant because they continue to have seizures after trying at least four of the many available medications for the disorder. Monitoring nearly 150 treatment-resistant men and women for up to three years, the study revealed that almost 70% of participants saw reductions in their average monthly seizure frequency. 

“Our findings challenge the assumption that once a patient with focal epilepsy has failed a certain number of antiseizure drugs, their chances of finding relief are small and not worth the effort,” said study lead author Ojas Potnis, MD, a resident in the Department of Neurology at the NYU Grossman School of Medicine. 

While the medications rarely stopped seizures altogether, they appeared to prompt longer periods between episodes. Almost 13% of the study volunteers went at least three months without a seizure, nearly 8% were seizure free for at least six months, and 3% had no seizures for a year or longer. 

While these percentages may seem small, Potnis notes that they are markedly higher than those identified in earlier studies, which stopped following patients after three months. This suggests that it may take more time for antiseizure drugs to start working for treatment-resistant patients, he says.

Publishing online Oct. 20, the report on the study is the second released in the journal JAMA Neurology by the Human Epilepsy Project, a multicenter effort to better understand how epilepsy patients respond to therapies. 

In the previous investigation, which published earlier this year, the researchers found that even those who respond well to medications (people with treatment-sensitive epilepsy) continue to have seizures for at least a year before their doctors find the right drug and dose for them. 

Ten epilepsy centers in the United States were involved in the new study, which took place from 2018 to 2021. The team collected data about the patients’ medical histories, demographic factors such as sex and race, and the details of their seizures, such as the frequency and type.  

During the study period, the patients tracked their seizure frequency in an electronic diary, noting either “seizure-free” or “had a seizure” for each day. The time, duration, and type of episode, along with other notes, were also recorded. The study volunteers reported information about their antiseizure medications too, indicating the type, dose, and reasons for discontinuing a regimen. In addition, they noted their experiences with any other forms of treatment such as surgery and use of neuromodulation devices, which are designed to stop seizures by sending an electrical signal through the nervous system. The research team followed up with each patient three times in six-month intervals. 

According to the results, 68% of participants had a reduction in seizure frequency during the second half of their involvement in the study compared with the first half. Taking an antiseizure medication appeared to make a difference — more than half of volunteers who experienced a decline in seizures started a new drug during the study. 

The findings also showed that the number of failed antiseizure medications had no effect on a patient’s likelihood of seizure reduction. 

“These results offer hope that focal epilepsy will get better over time for most people,” said study co-senior author and neurologist Jacqueline French, MD. “Health care providers should keep searching for the best treatment regimen for their patients no matter how many therapies they may need to try.” French is a professor in the Department of Neurology at NYU Grossman School of Medicine and co-principal investigator of the Human Epilepsy Project. 

French cautions that it remains unclear whether seizure reduction over time results from the natural way treatment-resistant epilepsy behaves or from management with interventions, since most of the study participants had ongoing adjustments to their therapies.

In the next stage of the Human Epilepsy Project, researchers plan to explore generalized epilepsy, another form of the disorder that occurs in about a quarter of people with epilepsy, says French.

Funding for the study was provided by UCB, Neurelis, and SK Life Science.

Along with French, Ruben Kuzniecky, MD, at Northwell Health in New York City, and Daniel Lowenstein, MD, at the University of California, San Franscisco, are study co-senior authors. They are also co-principal investigators for the Human Epilepsy Project. Other study co-investigators are Gabriel Biondo, BS, at the University of Notre Dame in Indiana; Rachel Sukonik, MLS, at Johns Hopkins Hospital in Baltimore; Caitlin Grzeskowiak, PhD, at the Epilepsy Foundation in Bowie, Maryland; Gary Cutter, PhD, at the University of Alabama at Birmingham; and Hamada Hamid Altalib, DO, MPH, at Yale University in New Haven, Connecticut.

French receives salary and research support from the Epilepsy Foundation and the Epilepsy Study Consortium. These organizations also covered fees for consulting or attending scientific advisory board meetings for Acadia Pharmaceuticals, Access Industries, Acuta Capital Partners, AfaSci, AgriThera, Alterity Therapeutics, Angelini Pharma, Autifony Therapeutics, Axonis Therapeutics, Beacon Biosignals, Biogen, Biohaven, Bloom Science, Bright Minds Biosciences, CAMP4, Capsida Biotherapeutics, Cerebral Therapeutics, Cerecin Neurosciences, Cerevel Therapeutics, Ceribell, Cognizance Biomarkers, Cowen and Co., Crossject, EcoR1 Capital, Eisai Co., Encoded Therapeutics, Engrail, EpiMinder, Epitel, Équilibre BioPharmaceuticals Corp., Genentech, GRIN Therapeutics, Harmony Biosciences/Epygenix Therapeutics, iQure Pharma, IQVIA, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Korro Bio, Leal Therapeutics, LivaNova, Longboard Pharmaceuticals, Marinus Pharmaceuticals, Modulight Biotherapeutics, Neumirna Therapeutics, Neurelis, Neurocrine Biosciences, Neurona Therapeutics, NeuroPace, NeuroPro Therapeutics, Neuroventis, Neurvati, Noema Pharma, Ono Pharmaceutical Co., Otsuka, Ovid Therapeutics, Praxis Precision Medicines, PureTech Health, Rapport Therapeutics, Receptor Holdings, RiverVest, Sage Therapeutics, SK Life Science, Stoke Therapeutics, Supernus Pharmaceuticals, Takeda Pharmaceuticals, Taysha Gene Therapies, Third Rock Ventures, UCB, uniQure, Ventus Therapeutics, Vida Ventures, and Xenon Pharmaceuticals. French has received additional research support from FACES, the One8 Foundation, the National Institute of Neurological Disorders and Stroke, and Praxis Precision Medicines. French serves on the editorial boards of The Lancet Neurology and Neurology Today and is the chief medical and innovation officer for the Epilepsy Foundation. She is the president and serves on the board of directors of the Epilepsy Study Consortium, and she has received travel/meal reimbursement related to research, advisory meetings, and presentation of results at scientific meetings from the Epilepsy Study Consortium, the Epilepsy Foundation, Biohaven Pharmaceuticals, Cerebral Therapeutics, Ceribell, Cowen and Co., Longboard Pharmaceuticals, Harmony Biosciences, LivaNova, MapLight Therapeutics, Neumirna Therapeutics, Neurocrine Biosciences, NeuroPace, Neurvati, Praxis Precision Medicines, Rapport Therapeutics, SK Life Science, Takeda Pharmaceuticals, Ventus Therapeutics, and Xenon Pharmaceuticals. 

The terms and conditions of all of these relationships are being managed in accordance with NYU Langone Health policies and procedures.

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