Abstracts

RATIONALE: Tuberous sclerosis complex (TSC) is a neurocutaneous disorder which possesses tow distinct genetic loci. The TSC 1 gene is on chromosome 9, with hamartin as its protein product. The TSC 2 gene is on chromosome 15 and produces the protein tuberin. The birth incidence of the disorder is estimated at 1 in 6,000-8,000. The gene exhibits highly variable clinical symptoms. Affected individuals have hamartonatous growths involving various organ systems; the brain, kidneys, heart, and skin are most often effected. Initially, identified by the triad of intractable epilepsy, mental retardation, and facial angiofibromas, it is now kown that this applies to no more than 30-40% of individuals with tuberous sclerosis. As many as 90% of individuals with TSC experience seizures, a signficant number suffer infantile spasms, intactable epilepsy, or Lennox-Gastaut syndrome.
Levetiracetam is a novel anticonvulsant for partial epilepsy. Its specific mechanism of action is unknown. It has no known hematologic or hepatic toxicity. We present our experience with the clinical treatment of epilepsy in seventeen individuals with tuberous sclerosis using levetiracetam. At the end of this activity, the participants should be able to discuss clinical situations in which levetiracetam may be effective in treating epilepsy in patients with tuberous sclerosis.
METHODS: We present our experience with levetiracetam therapy of epilepsy in tuberous sclerosis.The neurology records were reviewed for seventeen patients with tuberous sclerosis and epilepsy treated with levetiracetam in an unrandomized, open label study. Data gathered included change in seizure frequency and medication side effects while on levetiracetam. Additionally, tuber counts and diagnosis of autism were recorded. Assessments of efficacy were made at periodic follow-up visits or per telephone report from the parents.
RESULTS: The study group consisted of eight males and nine females with partial epilepsy. None of the patients were experiencing infantile spasms during treatment with levetiracetam. Eight individuals had TSC 2 mutations; one had TSC 1 mutation. Twleve cases were sporadic and five were familial. Levetiracetam treatment was initiated at 10 mg/kg/day divided bid to tid and titrated upward until either a clinical response or intolerable side effects were observed. Two individuals became seizure free. These subjects were experiencing relatively fewer seizures, from once per month to once per week. Five individuals experienced a greater than 50% reduction in seizure frequency. These individuals all had intractable epilepsy and had previously taken multiple seizure medications. Ten individuals did not respond meaning a less than 50% reduction in seizure frequency or no change was observed. Levetiracetam was withdrawn owing to hyperkinesis and agitation in two individuals, one with greater than 50% reduction in seizures and one non-responder. Number or location of tubers did not predict response to levetiracetam. Periodic monitoring of CBC, hepatic and renal profiles were undertaken. No clinically significant laboratory abnormalities were observed.
CONCLUSIONS: Levetiracetam is effective for the treatment of partial epilepsy and tuberous sclerosis and may have particular application for individuals with refractory epilepsy.