This study will examine the safety and effectiveness of infusing a chemical called muscimol
into the brain to control seizures in patients with intractable epilepsy (frequent seizures
that persist despite therapy). Muscimol, which is similar to a naturally occurring brain
chemical called GABA, has been shown to reduce seizures in rats. After the infusion study,
patients will undergo a standard surgical procedure for controlling seizures.
Patients 18 years of age or older with intractable epilepsy may be eligible for this study.
Before entering protocol 00-N-0158, candidates will be screened under protocol 01-N-0139,
Evaluation and Treatment of Patients with Epilepsy, with a medical history, physical and
neurologic examination, chest X-ray, electrocardiogram, blood and urine tests,
electroencephalographic (EEG) monitoring and magnetic resonance imaging (MRI) of the head.
Patients enrolled in this study will have the following procedures:
1. Computerized tomography (CT) and magnetic resonance imaging (MRI) of the head to guide
catheter/electrode placement (see #2).
2. Depth catheter/electrode placement into the presumed location of the seizure focus (the
part of the brain where the seizures originate) - A small hole is drilled through the
skull. A depth electrode with a hole in the center of the tubing is passed through the
brain into the structures usually involved in intractable epilepsy. MRI will be done to
check electrode placement. Video-EEG monitoring will continue for 5 days for this part
of the study. Patients will be tested for their ability to understand and produce
speech, see normally, move their arms and legs, distinguish sharp and dull objects, and
put pegs in a pegboard. They will be questioned about headache, weakness, numbness or
sleepiness. The electrode will be left in place for muscimol infusion (see #3).
3. Muscimol infusion - Into the seizure focus, patients will be given two infusions-one of
saline (salt water) alone and one of muscimol diluted in saline. Each infusion will be
given over a period of one-half to 5 1/2 days, infused at the rate of 0.1 ml (1/50th of
a teaspoon) per hour. During the infusions video-EEG recordings will continue and
patients will be interviewed and examined as described in #2 above).
4. Blood testing - About 2 tablespoons of blood will be drawn daily during the testing
period and for the first 2 days after surgery (see #5).
5. Surgery - Temporal lobectomy or topectomy (removal of a small, specific area of brain
tissue) is the standard surgical treatment for medically intractable epilepsy whose
seizure focus is not in a critical brain region, such as an area that controls language,
movement, or sensation. If the patient's seizures arise from one of these areas, an
alternative procedure called multiple subpial transection will be offered. In this
procedure, vertical cuts are made in the seizure focus to prevent neurons (nerve cells
that transmit electrical impulses) in the focus from spreading the seizure to the rest
of the brain.
6. Surgery follow-up - Patients will be monitored in the surgical intensive care unit for
24 to 48 hours and then in the NINDS nursing unit for 4 to 8 days before being
discharged to home. Another visit in the NINDS outpatient clinic will be scheduled for
6-12 weeks after surgery.
Phase:
Phase 1
Details
Lead Sponsor:
National Institute of Neurological Disorders and Stroke (NINDS)