Tumor Related Epilepsy

Objective

This protocol is being performed to 1) study the natural history and disease pathogenesis in
patients with tumor related epilepsy, 2) provide standard surgical treatment of brain tumors
with associated seizures, 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 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
and outcome assessments. Some patients may receive functional MRI when clinically indicated,
which will be performed under a separate protocol, 14-N-0061, Non-invasive pre-surgical
evaluation of patients with focal epilepsy. Invasive procedures include surgical resection of
the brain tumor and associated epileptogenic region. The ultimate goal of surgical resection
is to safely remove tumor tissue and to remove or modify the associated epileptic focus.
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 separte protocol,
11-N-0051 Epilepsy Surgery. Patients will be followed for three months after the surgical
procedure and will receive standard neurological examinations and MRI evaluation of the brain
as dictated by their care indicated for the brain tumor. 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 NINDS or NCI clinical trials.

Outcome Measures

The primary outcome measure is the change in seizure frequency, as measured by the Engel
scale before and 3 months after treatment. Secondary outcome measures include 1) mean Engel
Class three months after surgery stratified by the type of brain tumor and location and Engel
scale, seizure frequency, and mean Engel Class 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 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.