Protocol Number: 00-N-0158

Title:

Trial of Intracerebral Infusion in Patients with Medically Intractable Epilepsy

Number:

00-N-0158

Summary:

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.

Sponsoring Institute:

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

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

1. Be 18 years of age or older.

2. Have simple or complex partial seizures.

3. Seizures must persist at 6 or more per month, despite medical therapy.

4. Be able to give informed consent.

5. Have been determined by the NIH neurology staff to have medically intractable epilepsy.

6. Have a seizure focus in a single region of one cerebral hemisphere.

EXCLUSION CRITERIA:

Candidates will be excluded if they:

1. Are pregnant.

2. Have a contraindication to MRI scanning.

3. Have a bleeding disorder that cannot be corrected before testing or treatment.

4. Are unable to comprehend the risks of the testing and surgical therapy.

5. Have seizure foci in more than one region of one hemisphere or in both cerebral hemispheres.

6. Have a positive HIV test, because such patients would have increased risk of infection due to their immune deficiency.

Special Instructions:

Currently Not Provided

Keywords:

Video-EEG

Muscimol

Depth Electrode

Brain Catheter

Pharmacology

Epilepsy

Infusion

Magnetic Resonance Imaging

Recruitment Keyword(s):

Epilepsy

Condition(s):

Epilepsy

Investigational Drug(s):

Muscimol

Investigational Device(s):

None

Intervention(s):

Drug: Muscimol

Supporting Site:

National Institute of Neurological Disorders and Stroke

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Seizure control and mortality in epilepsy

Local perfusion of diazepam attenuates interictal and ictal events in the bicuculline model of epilepsy in rats

Effects of localized, chronic GABA infusions into different cortical areas of the photosensitive baboon, Papio papio

Heiss JD, Walbridge S, Morrison P, Hampton RR, Sato S, Vortmeyer A, Butman JA, O'Malley J, Vidwan P, Dedrick RL, Oldfield EH. Local distribution and toxicity of prolonged hippocampal infusion of muscimol. J Neurosurg. 2005 Dec;103(6):1035-45.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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