Epilepsy

David B. Burkholder, MD

Elaine C. Wirrell, MD

Epilepsy is one of the most common neurological disorders, affecting approximately one in 26 people over their lifetime. Epilepsy is defined as a disorder of the brain that is characterized by an enduring predisposition to generate epileptic seizures, and by the neurobiological, cognitive, psychological, and social consequences of this condition.[1] Holistic care for persons with epilepsy involves addressing both seizure control as well as these nonseizure manifestations.

Epilepsies are due to a diverse range of etiologies, including genetic, structural, metabolic, autoimmune, infectious, and unknown causes. Determining the underlying etiology as well as epilepsy type and/or electroclinical syndrome is critical to informing the best therapies and providing an accurate prognosis.

Epilepsy may have an age of onset at any time over the life span, with the highest rates in very young children as well as the elderly.

Early optimization of the treatment of epilepsy is critical not only for seizure control but also for decreasing or preventing the nonseizure comorbidities and stigma that are often associated with persisting seizures. In this issue, we begin with several articles addressing overall principles of medical treatment, including how to select and manage antiseizure medications and how to use polytherapy rationally in persons with epilepsy. Additionally, given that epilepsy is one of the most common neurological disorders in children, further discussion on the unique management considerations for the pediatric age range is provided.

Unfortunately, approximately 30% of persons with epilepsy are drug-resistant, which is defined as the failure of two or more appropriately chosen and used antiseizure medications to achieve seizure control. New antiseizure medications are emerging with novel mechanisms of action and improved tolerability, however, the likelihood that subsequent medications will control seizures after two or more have already failed is low. In such cases, nonpharmacologic options should be considered. The latter group of articles is focused on therapies for drug-resistant epilepsies, highlighting the breadth of therapies available, the selection of optimal candidates, and potential risks and benefits.

In properly selected patients, resective epilepsy surgery is associated with the highest likelihood of seizure freedom and should not be considered a therapy of last resort. Numerous techniques continue to advance the identification of the epileptogenic zone, including novel MRI imaging, functional imaging such as PET or SPECT, MEG, and invasive monitoring. The use of minimally invasive surgical techniques is expanding, minimizing complications and morbidity associated with epilepsy surgery. For those with drug-resistant epilepsy who are not candidates for resective or disconnective surgeries, advances in neuromodulation as well as dietary options promise the potential for significant seizure reduction and improved quality of life.

There have been tremendous advances in our understanding of the genetic contributions to epilepsy over the last decade. Increasingly, pathogenic monogenetic variants are found, which collectively lead to a significant proportion of drug-resistant epilepsies, particularly developmental and epileptic encephalopathies, which typically onset in early life. Several targeted genetic therapies are currently in clinical trials for specific developmental and epileptic encephalopathies, which could potentially prevent or ameliorate developmental impairment as well as seizures; however, early initiation of treatment will likely be key to obtaining optimal results.

Additionally we include an article that focuses on management of autoimmune epilepsies, where early use of immunomodulatory therapies may be key in improving outcome.

While there have been significant advances in our ability to determine the underlying etiology of epilepsy, as well as in improving therapies for persons with drug-resistant epilepsies, many persons with epilepsy continue to struggle with refractory seizures and their sequelae, and thus we still have work to do!

We thank our authors for these high-quality, state-of-the-art articles, and also wish to extend our thanks to Dr. Greer and the staff of “Seminars in Neurology” for allowing us to present updates in epilepsy treatment.

Publication History

Article published online:
08 May 2025

• Reference

• 1 Fisher RS, van Emde Boas W, Blume W. et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005; 46 (04) 470-472