NINDS recognizes National Epilepsy Awareness Month

NINDS Deputy Director Ann Poduri, MD, MPH, and NINDS Director Walter J. Koroshetz, MD

In honor of National Epilepsy Awareness Month, we would like to highlight the current state of epilepsy research and the role of epilepsy. nines We support research to better understand, diagnose, treat, and ultimately prevent epilepsy.

epilepsy It is a neurological disease characterized by repeated seizures caused by abnormally synchronized brain activity. Epilepsy affects people of all ages and the lifetime prevalence of epilepsy worldwide is 1 in 26 people, meaning it affects 1 in 26 of us. Epilepsy often begins in childhood, with an estimated 500,000 children (ages 0-17 years) living with epilepsy in the United States, making it one of the most common childhood neurological disorders. What we call “epilepsy” is due to many underlying causes and associated symptoms. In about half of those diagnosed, epilepsy is associated with infections, head trauma, genetic causes, prenatal trauma, and other causes. Others continue to experience seizures and related symptoms without an identified cause and are presumed to have some genetic susceptibility.

The most common way to treat epilepsy is with antiepileptic drugs. a Research published todaysupported by nineshave shown that two common antiepileptic drugs used during pregnancy (lamotrigine and levetiracetam) do not adversely affect children's neurological development. Treatment of epilepsy during pregnancy is difficult and complex, but this long-term study provides valuable insight for pregnant women with epilepsy.

Antiepileptic drugs are effective for many people with epilepsy, but about one in three people with epilepsy develops “drug-resistant” seizures that persist despite multiple medications. Additionally, many antiepileptic drugs have significant side effects. To address the unmet need for effective and well-tolerated anti-seizure drugs, nines created EEpilepsy treatment screening program The program's current focus is on discovering drugs to treat drug-resistant epilepsy and to prevent and ameliorate the disease.

Surgery may also be considered if drugs do not control seizures or if doctors identify a distinct “seizure focus” in the brain. Research supported by NINDS. Brain research powered by innovative advances in neurotechnology® Initiative, or BRAIN Initiative®continues to refine methods to map seizure activity in the brain to guide surgical interventions. in nines It is run by Dr. Sarah K. Inati of the Intramural Programs Department. Epilepsy Neurophysiology Unit. Her lab uses non-invasive imaging approaches for individuals being evaluated for epilepsy surgery to determine where seizures begin and model how they spread in the brain.

To support better treatment and prevention of epilepsy, we need to know more about the causes of epilepsy, including the genes and pathways associated with it. In 2010, nines We launched the Center Without Walls for Collaborative Research in Epilepsy (CWoW), bringing together multidisciplinary teams from across the country to tackle epilepsy challenges. epilepsy research. After 4,000 patients with epilepsy were enrolled through the Epilepsy Phenomena/Genome Project; The Epi4K consortium has begun an effort to sequence the DNA of these 4,000 people.. The first big discovery was something new “Candidate gene” for childhood epilepsy It continues to be deeply studied today. Thanks to the Epi4K consortium, other NINDS-supported research institutions, and an extensive network of international collaborators, we have moved from a small number of epilepsy genes 20 years ago to hundreds of epilepsy genes today. Epi4K's efforts are now expanding around the world. Epi25 collaboration With support from the National Human Genome Research Institute.

my early days [Poduri’s] During my career, I discovered that epilepsy can be caused by “somatic mutations.” This refers to genetic mutations that occur after conception and leave genetic variants in some of an individual's cells. For example, if a mutation occurs early in prenatal development in a single progenitor to a subset of brain cells, the mutation will replicate across all cells derived from the affected progenitor and result in brain malformations. Associated local areas may arise. Epilepsy and intellectual disability. These abnormal areas contain genetically normal cells and cells with genetic mutations that disrupt brain function, resulting in a “mosaic” pattern. We discovered mosaic somatic mutants. hemimegalencephalya malformation of half the brain associated with severe and intractable epilepsy. Specifically, they discovered somatic variants that involve genes in specific signaling pathways involving a protein called mammalian target of rapamycin (mTOR).

Researchers and clinicians can now use deep sequencing technology to find somatic mutations within surgically removed brain tissue. The rate of identifying specific genetic causes of epilepsy associated with brain malformations increases from 0% to 50% for small lesions, such as focal cortical dysplasia, routinely seen in epilepsy clinics; also increased from 0% to 80% for rare malformations. , hemiencephaly, etc.

Although we have identified many genes associated with epilepsy, there is still much to discover. Additionally, we now have an opportunity to bridge the gap between scientific discovery and providing accurate diagnosis for patients with active epilepsy. inside me [Poduri’s] Through our own research and partnerships with other pediatric hospitals, we are finding that nearly half of infants with new-onset epilepsy, whether seen in neonatal intensive care units or neurology clinics, have a rapidly identifiable genetic cause. It has been confirmed that it has an immediate effect. About diagnosis, prognosis, and clinical care. With partial funding from NIH (National Institutes of Health)My group and many others have been working with family-led foundations to create registries of individuals with pathogenic variants.. These registries provide important information to people with lived experiences about opportunities to contribute to research and share findings that influence decisions about care. nines We will continue to prioritize the perspectives of people with lived experience of epilepsy in our epilepsy research priorities.

Recognizing that there are many important unmet research needs in epilepsy and that this field is rapidly evolving, nines We have long partnered with the epilepsy research community, the American Epilepsy Society (AES), and the broader community to assess the current state of epilepsy research and development. Benchmarks in epilepsy research. nines Hosting a “Cure the Epilepsies” conference, where interested groups such as researchers, clinicians, epilepsy patients and their families, advocates, and representatives from nonprofit foundations come together to identify future research priorities to incorporate into benchmarks I'm doing it. Through this study, the epilepsy community recognizes the continued need for basic research into the molecular and network abnormalities underlying epilepsy, as well as research into the effects of comorbidities, antiepileptic drug side effects, and sudden death in epilepsy (SUDEP). I recognized it. .

In addition to the collaboration between Epi4K and Epi25 mentioned above, nines Supported the following CWoW for collaborative research in the field of epilepsy: 1) SUDEP Research CenterResearch the incidence, biomarkers, risk identification and prevention of SUDEP. 2) Epilepsy bioinformatics research for antiepileptic treatment (EpiBioS4Rx), to identify biomarkers to predict who is likely to develop epilepsy after traumatic brain injury. 3) Channelopathy-related epilepsy research centerused high-throughput techniques (such as stimulating and recording hundreds of neurons simultaneously) to determine the effects of genetic mutations identified in ion channels. and 4) Multiplatform variant prediction for epilepsy (EpiMVP) project. We focus on mutations in nonionic channel epilepsy genes of unknown significance. These large-scale studies have spawned new collaborations, training, and research that continue well beyond the five-year funding period for these centers. nines We also support a broad portfolio of investigator-initiated epilepsy research, including basic, translational, and clinical research.

nines We are deeply engaged in Improving health equity for neurological diseases Understand how social determinants play a role in disease prevalence, access to care, and health outcomes, including epilepsy. of latest research From Rebecca Gottsman, M.D., Senior Research Scientist at ninesshowing that self-reported sexual and sexual minorities (SGM) are twice as likely to report active epilepsy compared to their non-SGM peers. These findings highlight the importance of collecting SGM status in research and the need for targeted research on SGM populations. In addition, NINDS Senior Investigator and current AES President William Theodore, M.D., facilitated the work of the AES/International League Against Epilepsy-North American Joint Task Force on Epilepsy Care Disparities. The task force was established in 2023 to investigate the healthcare disparities experienced by people with epilepsy. Make recommendations to address these disparities. in ninesWe ensure that the exciting epilepsy research efforts we support are inclusive and accessible to individuals with epilepsy, regardless of age, gender, race, income, or geographic location. I am thinking of doing so.

What we are proud of is nineshas historic and ongoing support for epilepsy research and looks forward to building on these past successes to further advance the understanding, diagnosis, treatment, and ultimately prevention of epilepsy . Through ongoing partnerships with scientists, clinicians and experienced people, we are committed to a better future for people with epilepsy.