Phase II Randomized Study of Early Surgery Vs Multiple Sequential Antiepileptic Drug Therapy for Infantile Spasms Refractory to Standard Treatment

Study Overview
=================
Brief Summary
-----------------
OBJECTIVES: I. Evaluate the efficacy of surgical resection of an identifiable zone of cortical abnormality versus multiple drug therapy in children with infantile spasms refractory to standard therapy. II. Assess how infantile spasms interfere with development and whether this is partially reversible. III. Determine the predictors of good surgical outcome and whether surgery permanently controls seizures and improves development.

Detailed Description
-----------------
PROTOCOL OUTLINE: This is a randomized study. Patients are randomly assigned to 1 of 2 treatment groups. The first group undergoes sequential antiepileptic therapy with pyridoxine, corticotropin, valproic acid, carbamazepine, and nitrazepam. The sequence of administration may be altered based on drugs taken prior to entry. Any drug may be omitted due to medical contraindications or prior use at study doses or higher. The second group undergoes surgical resection of the zone of cortical abnormality. A functional hemispherectomy is performed for hemiparesis or diffuse unihemispheric dysfunction. If seizures are controlled in the first group at 3 months, the current medication is maintained; if seizures are not controlled, sequential therapy continues to completion. Patients experiencing uncontrolled seizures at 6 months cross to surgery. Surgical patients experiencing uncontrolled seizures at 3 months or persistent seizures after taper of pre-study antiepileptics cross to drug therapy. All patients are followed at 6 months and 1, 2, 3, 5, 7, and 10 years.

Conditions
-----------------
Spasms, Infantile, Epilepsy

Intervention / Treatment
-----------------
* Drug: carbamazepine
* Drug: corticotropin
* Drug: nitrazepam
* Drug: pyridoxine
* Drug: valproic acid
* Procedure: Surgery


Participation Criteria
=================
Eligibility Criteria
-----------------
PROTOCOL ENTRY CRITERIA: Disease Characteristics Infantile spasms or seizures with diagnosis based on the following: short muscular contractions leading to flexion or extension; Single or repetitive electroencephalogram (EEG) consistent with diagnosis, i.e., hypsarrhythmia, modified hypsarrhythmia, multifocal spike and wave abnormalities; developmental quotient less than 70 Zone of cortical abnormality in 1 lobe, contiguous multilobes, or 1 hemisphere; confirmed by historical, neurological, and physical evidence, including EEG, closed circuit televised EEG, computed tomography, magnetic resonance imaging, and/or positron-emission tomography; at least 2 abnormal test/imaging results required No treatable seizure etiology such as metabolic disease or infection Prior/Concurrent Therapy Failed standard therapy, i.e., refractory to corticotropin (at least 40 IU/day for 14 days) as follows: persistent infantile spasms OR recurrent spasms after discontinuation or taper OR complications requiring dose modification At least 1 month of standard antiepileptic drug with documented therapeutic blood levels Patient Characteristics No medical contraindication to surgery English-speaking family

Ages Eligible for Study
-----------------
Minimum Age: 0 Years
Maximum Age: 2 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: carbamazepine|nan|
|Drug: corticotropin|nan|
|Drug: nitrazepam|nan|
|Drug: pyridoxine|nan|
|Drug: valproic acid|nan|
|Procedure: Surgery|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
infantile spasms, epilepsy, neurologic and psychiatric disorders, rare disease, seizures