Surgery as a Treatment for Medically Intractable Epilepsy
Surgery as a Treatment for Medically Intractable Epilepsy
Background:

 - Medically intractable epilepsy is the term used to describe epilepsy that cannot be
 controlled by medication. Many people whose seizures do not respond to medication will
 respond to surgical treatment, relieving seizures completely or almost completely in one-half
 to two-thirds of patients who qualify for surgery. The tests and surgery performed as part of
 this treatment are not experimental, but researchers are interested in training more
 neurologists and neurosurgeons in epilepsy surgery and care in order to better understand
 epilepsy and its treatment.

 Objectives:

 - To use surgery as a treatment for medically intractable epilepsy in children and adults.

 Eligibility:

 - Children and adults at least 8 years of age who have simple or complex partial seizures
 (seizures that come from one area of the brain) that have not responded to medication, and
 who are willing to have brain surgery to treat their medically intractable epilepsy.

 Design:

 -  Participants will be screened with a medical history, physical examination, and
 neurological examination. Imaging studies, including magnetic resonance imaging and
 computer-assisted tomography (CT), may also be conducted as part of the screening.
 Participants who do not need surgery or whose epilepsy cannot be treated surgically will
 follow up with a primary care physician or neurologist and will not need to return to
 the National Institutes of Health for this study.

 -  Prior to the surgery, participants will have the following procedures to provide
 information on the correct surgical approach.

 -  Video electroencephalography monitoring to measure brain activity during normal
 activities within a 24-hour period. Three to four 15-minute breaks are allowed within
 this period.

 -  Wada test to evaluate speech, comprehension, and memory centers of the brain, using a
 contrast dye to study the blood vessels of the brain and a short-term anesthetic
 administration procedure to test the effects on areas of speech and memory.

 -  Depth electrodes and/or brain surface electrodes to measure brain activities and
 determine the part of the brain that is responsible for the seizures (seizure focus).

 -  Participants will have a surgical procedure at the site of their seizure focus. Brain
 lesions, abnormal blood vessels, tumors, infections, or other areas of brain abnormality
 will be either removed or treated in a way that will stop or help prevent the spread of
 seizures without affecting irreplaceable brain functions, such as the ability to speak,
 understand, move, feel, or see.

 -  Participants will return for outpatient visits and brain imaging studies 2 months, 1
 year, and 2 years after surgery.
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.