Brain Damage Newsroom

Brain Infusion of Muscimol to Treat Epilepsy

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. Candidates will be screened under protocol (75-N-0124 - Monitoring of Seizures, EEG and Serum Antiepileptic Drug Concentrations in Patients with Uncontrolled 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 or possible location of the seizure focus (the part of the brain where the seizures originate) - Small holes are drilled through the skull. Electrodes with a hole in the center of the tubing that holds them are 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 in patients in whom the location of the seizure focus is known but longer (up to 33 days) in patients in whom the seizure focus is difficult to locate. 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 electrodes will be left in place for muscimol infusion (see #3), except in patients in whom a seizure focus cannot be located. Patients in whom a seizure focus cannot be located will not receive muscimol infusion or undergo surgery.

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 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.