Tumor Related Epilepsy
Tumor Related Epilepsy
Background:

 Some people with brain tumors have seizures related to the tumor. This is called
 tumor-related epilepsy. Usually brain tumors are treated by removing as much of the brain
 tumor as possible without causing problems. Researchers think this may improve the outcome
 for people with brain tumors. It may completely relieve or greatly reduce the number of
 seizures they have.

 Objectives:

 To evaluate people with brain tumors that are associated with seizures and to offer surgical
 treatment. Also, to study how surgery affects seizures.

 Eligibility:

 People age 8 and older who have a brain tumor with associated seizures. They must be willing
 to have brain surgery to treat their epilepsy.

 Design:

 Participants will be screened with a review of their medical records.

 Participants will have a medical history and physical exam.

 Participants will be admitted to the hospital at NIH. They will have

 Medical history

 Physical exam

 Neurological exam

 Tests of memory, attention, and thinking

 Questions about their symptoms and quality of life

 Blood drawn

 They may also have:

 MRI or CT scan. They will lie on a table that slides in and out of a machine that takes
 pictures. For part of the MRI, they will get a dye through an intravenous (IV) catheter.

 Video electroencephalography monitoring. Electrodes will be placed on the scalp. The
 participant s brain waves will be recorded while doing normal activities. Participants will
 be videotaped.

 Participants will keep a seizure diary before and after surgery.

 Participants will have surgery to remove their brain tumor and the brain area where their
 seizures start.

 They will stay in the hospital up to a week after surgery.

 Participants have for follow-up visits at NIH.
Objective

 This protocol is being performed to 1) study the natural history and disease pathogenesis in
 patients with tumor related epilepsy, 2) collect prospective data on seizure outcomes
 following standard surgical treatment of brain tumors with associated seizures2, 3) follow
 the clinical course of patients after surgical resection of brain tumors with associated
 seizures, such as outcomes in seizure activity as they relate to type of tumor and extent of
 resection, 4) investigate neuropsychological and cognitive outcomes as they relate to
 surgical and seizure outcomes, 5) evaluate patient reported outcomes such as symptom burden
 changes as a result of surgical resection in patients with tumor-related epilepsy, 6) examine
 changes in structural and, when available, functional imaging in the context of tumor related
 epilepsy before and after surgical resection, 8) investigate molecular markers of
 tumor-related seizures in tumor and peritumoral specimens and, when available, to compare
 them to electrophysiological markers of tumor-related seizure activity.

 Study Population

 Patients 8 years and older with brain tumors and associated seizures may participate in this
 study.

 Study Design

 Patients will be screened by study neurosurgeon or neuro-oncologists to verify their
 confirmed or likely diagnosis of brain tumor and associated seizures. Patients confirmed to
 have a brain tumor with associated seizures will be offered standard diagnostic and surgical
 procedures. Non-invasive diagnostic procedures include structural MRI and neuropsychological,
 cognitive, and outcome assessments which may be performed under other NIH protocols. Some
 patients may receive functional MRI when clinically indicated, which will be performed under
 separate NIH protocols. Prior to tumor resection, diagnostic invasive monitoring with
 intracranial electrodes for further localization of seizure focus and identification of
 eloquent cortex may be clinically required. In these cases, invasive monitoring will be
 performed under a separate protocol, 11-N-0051 Epilepsy Surgery. Patients will be followed
 for three-six months after the surgical procedure to collect prospective data on seizure
 outcomes following standard surgical treatment of brain

 tumors with associated seizures. Patients may also be seen at one year following surgery if
 medically stable and healthy. Participants in this protocol will not forego other standard
 treatments for their brain tumor, including chemotherapy and radiation treatment.
 Participation in this protocol will not preclude eligibility or participation in other NIH
 clinical trials.

 Outcome Measures

 The primary outcome measure is the change in seizure frequency, as measured by the Engel
 scale before and 3-6 months after treatment. Secondary outcome measures include 1) mean Engel
 Class and absolute and relative change in seizure frequency three-six months after surgery
 stratified by the type of brain tumor and location and Engel scale, seizure frequency, and
 mean Engel Class and absolute and relative change in seizure frequency one year after surgery
 stratified by the type of brain tumor and location; 2) extent of tumor and peri-tumoral
 resection as seen on MRI imaging and correlation with seizure outcome; 3) changes in
 neuropsychological and cognitive assessment following surgical resection stratified by
 location and type of tumor and extent of resection; 4) longitudinal changes in symptom burden
 and interference scores using established instruments in brain tumor patients; 5) changes in
 structural imaging following surgical resection; 6) change in the use of anti-epileptic
 medication; and 7) percentage of patients with permanent neurological side-effects from
 surgical treatment.
-  INCLUSION CRITERIA:

 To be eligible for entry into the study, a candidate must meet all the following criteria:

 -  Be 8 years of age or older.

 -  Have solitary primary or recurrent brain tumor with associated seizures. Brain tumor
 may be diagnosed radiologically. Associated seizures are defined as those with
 activity starting within three months of radiologic diagnosis of the primary or
 recurrent tumor. In cases when the timing of seizure activity is unclear with respect
 to the timing of diagnosis, seizures will be considered associated with the tumor if
 seizure semiology is consistent with that location. Ongoing seizures are not required.
 Patients can be included if they have had a single previous seizure. Patients who have
 not experienced seizures after institution of anti-convulsant therapy are not
 excluded.

 -  Agree to undergo brain surgery.

 -  Willing and able to appoint a durable power of attorney.

 EXCLUSION CRITERIA:

 Candidates will be excluded if they:

 -  Have a bleeding disorder that cannot be corrected before invasive testing or surgery,
 or other medical conditions that would make surgery unsafe, such as lung or cardiac
 disease that would render them unable to tolerate the risk of general anesthesia, or
 severe immunodeficiency or systemic cancer not related to a brain lesion.

 -  Cannot have an MRI scan.

 -  Have multiple brain tumors, evidence of carcinomatous meningitis, gliomatosis cerebri,
 or primary CNS lymphoma. Patients with multiple metastatic lesions that for which
 surgery is not indicated will be exluded. Patients with peripheral neurological or
 systemic metabolic disorders that cause seizures will be excluded.

 -  Have an underlying seizure disorder that is unrelated to the brain tumor, or
 underlying neurological disorder that is unrelated to the brain tumor and that may
 contribute to seizure activity.

 -  At the time of enrollment, lack consent capacity due to cognitive impairment that
 would make them incapable of understanding the explanation of the procedures in this
 study. Cognitive capacity to consent will be determined at the time of enrollment.
 Patients with mental disorders or those patients who are cognitively impaired yet
 still retain consent capacity will not be excluded. Children may be enrolled if there
 is a parent or guardian able to consent on their behalf.