Abstracts

Infantile spasms is a catastrophic epilepsy of the young child associated with a hypsarrthymic EEG and poor long-term outcome. Current conventional treatments include ACTH and valproate which show limited efficacy and are associated with high morbidity and mortality in this population. Vigabatrin has demonstrated efficacy in infantile spasms but is not available in the United States. The purported mechanism of action is through elevation of whole brain GABA.Tiagabine raises brain GABA levels by blocking reuptake. We performed a pilot study of tiagabine for treatment of infantile spasms. Patients age 1-36 months with infantile spasms experiencing at least one cluster of spasms per day for three days prior to enrollment with an EEG containing hypsarrthymia or modified hypsarrthymia were recruited for a prospective open label study of tiagabine as first line therapy. Dosing started at 0.2 mg/kg/day and increased every 3 days by 0.2 mg/kg/day until resolution of seizures, intolerability or a maximum dosage of 5 mg/kg/day.MRI[apos]s of the brain were obtained prior to enrollment to confirm the absence of a progressive lesion. Patients were evaluated weekly during titration and every 2 weeks during stabilization. Patients were recruited between 10/00 and 11/01. 5 patients were enrolled (3 female, 2 male) ages 6-10 months. At baseline patients experienced 3 - 7 spasm clusters/day. 2 patients had been diagnosed previously with a seizure disorder prior to development of spasms. All had symptomatic spasms (2 with trisomy 21, 1 traumatic brain injury, 1 tuberous sclerosis, 1 with porencephaly). 3 patients experienced resolution of hypsarrthymia and cessation of spasms. 2/3 developed other seizure types, 1 focal tonic,1 generalized tonic with development of a slow spike wave EEG. 2 demonstrated no efficacy with one withdrawing at low dose due to intolerability (sedation). Hematology and chemisrty labs including liver function tests were monitored during the study. No clinically significant changes in lab values occurred. In this pilot study, tiagabine demonstrated efficacy in infantile spasms with 3/5 showing resolution of hypsarrthymia and control of spasms.No life threatening reactions were noted and compared to current therapies were well tolerated.
Tiagabine demonstrates potential as treatment for infantile spasms.Tiagabine has a superior safety profile compared to treatments available in the United States. Further studies are warranted to determine its exact role. (Supported by Abbott Laboratories supplied drug at no cost)