Abstracts

Rationale: Angelman Syndrome (AS) is a genetic disorder which occurs in approximately 1 in 10,000 to 20,000 births. Characteristics of AS include an ataxic gait, jerky limb movements, microcephaly with global developmental delays, severe expressive and receptive language impairment, and happy disposition. Epilepsy occurs in more than 80% of those with AS and is often intractable. We sought to examine a large cohort of patients with the goal of finding the most effective treatments for epilepsy in AS. Methods: An in-depth questionnaire was electronically conducted through the Angelman Syndrome Foundation. The survey included detailed questions pertaining to the different types of treatments used for epilepsy in AS patients. Results: The survey yielded a respondent total of of 461; 56% were male, 44% were female. The current average age of the AS patients was 13.9 years (1.3 – 45 years) with an average age at diagnosis of AS of 5.3 years. A total of 396 (86%) had epilepsy with an average age of onset at 3.8 years. Treatment of epilepsy among this population consisted of the use of anticonvulsant drugs (ACD) by all AS patients. Fifteen percent responded to the first medication used, whereas 78% were refractory to the first two medications and 64% had tried multiple medications (average of 3.2 medications). Of those who were refractory, 26% became seizure free with further treatment. At the time of data collection 40% were being treated with monotherapy (average current treatment of 1.2 medications). The most common of greater than 20 different medications tried were: valproate 62%, clonazepam 34%, phenobarbital 30%, topiramate 30%, lamotrigine 24%, carbamazepine 24%. For those who tried multiple medications the most effective were valproate, nitrazepam, levetiracetam, lamotrigine, clorazepate, topiramate, and clonazepam. The medications perceived by the respondents to have the most negative side effects were ACTH, carbamazepine, phenobarbital, oxcarbazepine. Seventeen percent of respondents had also used non-pharmacologic treatments for epilepsy. These included dietary therapy with the classic ketogenic diet in 31/396 (8%) and the low glycemic index treatment in 7/396 (2%). Of those that tried the ketogenic diet, 36% felt it was the most effective treatment. The vagal nerve stimulator was used by 16/396 (4%) of the AS patients, and it proved the most effective treatment for 3 of the 16. Two of the 396 (<1%) AS patients had undergone corpus callosotomies. Conclusions: Epilepsy occurs in over 80% of individuals with AS. In our population, the majority of AS patients were treated with more than 3 medications prior to achieving seizure control. Several of the new ACDs with broad spectrum efficacy were successful at providing seizure control and were well tolerated. Seizure freedom was achieved by 66% of AS patients with either ACD monotherapy or polytherapy. Dietary therapy and the vagus nerve stimulator also appeared to significantly reduce seizures in individuals with AS.