Surgery as a Treatment for Medically Intractable Epilepsy

Objective This protocol is being performed collect prospective data on patients who receive standard care therapy for drug resistant epilepsy and to follow the therapeutic course of patients from pre-operative evaluation, through surgery, and post-operatively, and to collect prospective data on seizure outcomes following surgery to add to the body of knowledge in this field. Primary outcome measures will be used to assess efficacy of surgery for clinical care purposes. Any treatment under this protocol will be based on the current standard of care for epilepsy surgery. The secondary goals of this protocol will be to investigate neurophysiological correlates of human cognitive function and to provide invasive monitoring for patients with tumor related epilepsy. Study Population Patients 8 years and older whose seizures are uncontrollable with medication may participate in this study as well as patients with tumor related epilepsy in whom invasive monitoring is indicated. Study Design Patients will be screened by study neurologists to confirm their diagnosis of drug resistant epilepsy. Patients that do not have a confirmed diagnosis of drug resistant epilepsy will be offered further evaluation in protocol 18-N-0066, Investigating Epilepsy: Screening,Evaluation and Treatment. Patients confirmed to have drug resistant epilepsy will be offered standard invasive and non-invasive diagnostic and surgical procedures. Diagnostic invasive monitoring with intracranial electrodes for further localization of their seizure focus may be required. The ultimate goal is to surgically remove or modify the epileptic focus. Standard procedures to be performed are 1) anterior temporal lobectomy or 2) amygdalohippocampectomy for temporal lobe epilepsy, 3) focal cortical resection for epilepsy that arises outside the temporal lobe, 4) removal of brain lesions causing epilepsy, and 5) multiple subpial transection. In patients in whom invasive monitoring is medically necessary, neurophysiologic activity during cognitive tasks will be captured from intracranial surface and depth electrodes. Analysis will focus on the role of neuronal firing and aggregate neural activity 1) during cognitive function, 2) in other states such as wakefulness and sleep, and 3) during periods of time surrounding seizure activity. Drug Resistant Epilepsy Patients with drug resistant epilepsy will be followed for two years after the surgical procedure and will receive standard neurological examinations and MRI evaluation of the brain. Patients who do not have surgical resection of epileptogenic tissue will complete participation after the three-month post-op visit. Participants in this protocol will be evaluated for potential eligibility for other NINDS clinical trials. Tumor Related epilepsy Patients with tumor related epilepsy will be enrolled in this protocol because of clinical indications arising from participation in a seperate protocol, 16-N-0041 Tumor Related Epilepsy. Patients will complete participation after the three-month post-op visit. Outcome Measures The primary goal of this protocol is to collect prospective data on patients who receive standard care therapy for drug resistant epilepsy, and to determine the efficacy of surgery for treatment while collecting physiology, tissue, and behavioral data for research.The primary outcome measure for patients with drug resistant epilepsy is the change in seizure frequency, as measured by the Engel scale before and 1 year after treatment. Secondary outcome measures include 1) percentage of patients who are able to be completely withdrawn from anti-epileptic medication; 2) percentage of patients who are seizure-free (Engel Class I); 3) mean Engel Class one year after surgery stratified by the type of surgical procedure; 4) percentage of patients with permanent neurological side-effects from surgical treatment; and 5) neurophysiological correlates of cognitive function. Outcomes for patients with tumor related epilepsy will be assessed under a seperate protocol, 16-N-0041, Tumor Related Epilepsy.

- INCLUSION CRITERIA: To be eligible for entry into the study, candidates must meet all the following criteria: 1. Be 8 years of age or older with drug resistant epilepsy or tumor related epilepsy. 2. Have focal onset seizures. 3. Seizures must persist despite medical therapy (drug resistant epilepsy) or seizures must be associated with the presence of a brain tumor. 4. Able to give informed consent, or have a parent able to provide informed consent if a child. 5. Agree to undergo brain surgery if indicated to treat drug resistant epilepsy. EXCLUSION CRITERIA: Candidates will be excluded if they: 1. Are pregnant (subjects of childbearing age will be tested with a urine pregnancy test and will have agreed to avoid being pregnant by practicing a reliable form of contraception or by abstinence from sexual intercourse while undergoing evaluation for epilepsy surgery and for 1 month after epilepsy surgery). 2. Cannot have an MRI scan. 3. Have a bleeding disorder that cannot be corrected before invasive testing or surgery, or other medical conditions which would make testing or surgery unsafe, such as lung or cardiac disease which would increase the risk of general anesthesia or severe immunodeficiency or systemic cancer not related to a brain lesion.

Study Location