Abstracts

Rationale: Myoclonic-Astatic Epilepsy of Doose is a generalized epilepsy syndrome with seizure onset between 2-5 years of age, myoclonic-astatic-absence seizures with or without tonic seizures, and an electroencephalogram demonstrating irregular generalized polyspike and slow wave complexes in the context of normal background activities. The seizures are often refractory and standard antiepileptic medications have limited efficacy. Most of these children have associated cognitive and behavioral dysfunction. This study was undertaken to evaluate the efficacy of felbamate in the treatment of myoclonic-astatic epilepsy of Doose. Methods: We conducted a retrospective chart review of our epilepsy database and identified 8 patients who met the criteria for Myoclonic-Astatic Epilepsy of Doose. All patients had onset of epilepsy between 2.5-5 years of age; all but one were boys. Their primary seizure type was absence seizures with myoclonic and astatic components. All of them had multiple daily seizures. All patients had long term video EEG monitoring, which demonstrated frequent high amplitude, generalized, irregular polyspike, spike, and slow wave discharges in the context of a normal background. Multiple electroclinical seizures were recorded and documented absence seizures with myoclonic-astatic components. All of the patients had co-morbid cognitive and behavior dysfunction, typically attention deficit hyperactivity disorder (ADHD). All patients had failed multiple antiepileptic medications, including valproate, topiramate, lamotrigine, clobazam, levetiracetam, and/or ethosuximide, prior to the initiation of felbamate. Results: The 8 pediatric patients (ages 3.5 to 12 years old) with refractory Myoclonic-Astatic Epilepsy of Doose were started on felbamate, initially as adjunctive therapy. Six out of the 8 patients have remained seizure-free on felbamate monotherapy for an average of 21 months (range: 6 months to 4 years). The two remaining patients have had a greater than 75% reduction in seizure frequency within 4 and 6 months respectively and have been tapered off of most of their other antiepileptic medications. They remain on felbamate and one other antiepileptic therapy (clonazepam and ketogenic diet, respectively). The felbamate dosage has ranged from 35-75mg/kg/day with trough levels of 20-99 mcg/ml, with 90% of the patients being on 35-50 mg/kg/day. Only 3/8 patients have had significant side effects, i.e. insomnia and gastrointestinal symptoms. The side effects have been effectively treated with the combination of melatonin and cyproheptadine. None of the patients have had significant or life-threatening hematological side effects or liver dysfunction. With the improvement in seizure control, there has been a significant improvement in cognitive abilities and attention and concentration. Conclusions: On the basis of this small study, felbamate appears to be highly effective in the treatment of medically refractory Myoclonic Astatic Epilepsy of Doose, with patient dosages generally less than 50mg/kg/day.