Abstracts

Rationale: Felbamate can be used in the treatment of partial seizures as well as primary generalized seizures in patients with Lennox-Gastaut syndrome. Besides its antiepileptic efficacy, some antiparkinsonian benefits have been ascribed to felbamate. We report the development of acute abnormal involuntary movements in a patient recently started on felbamate as adjunctive therapy. Methods: This is the case of a 34 year-old man with a history of Lennox-Gastaut syndrome with several seizure semiologies, consisting predominantly of atypical absence seizures with associated myoclonic seizures and tonic seizures on treatment with pregabalin, valproic acid and levetiracetam. Due to concern for depressed mental status related to either pharmacological oversedation versus increased frequency of unrecognized seizures, he was admitted to the epilepsy monitoring unit (EMU). He was noted to have frequent atypical absence seizures and more than 30 tonic seizures daily. Felbamate was introduced and titrated up from 600mg TID to 1200mg TID over the course of 4 days and then pregabalin was reduced from 150mg BID until discontinuation due to complaint of oversedation. Results: One week after felbamate was titrated up to 1200mg TID, he presented to the emergency room with continuous involuntary movements. These movements would interfere with his caretaking, including feeding and repositioning. Neurological exam revealed normal alertness, choreic movements of head and trunk, upper limbs dystonia, and orofacial dyskinesias. EEG showed abundant interictal multifocal epileptiform discharges, generalized paroxysmal fast activity, and generalized slow spike-wave and polyspikes-wave discharges. There were frequent tonic seizures, atypical absence seizures, and subclinical seizures lasting up to 15 seconds, occurring up to 50 times a day. VPA level on admission was 130 ug/mL (baseline: 89 ?" 131 ug/mL), levetiracetam level was 55 ug/mL, and felbamate level was 108 ug/mL. Ammonia level was unremarkable at 68 umol/L. As felbamate was tapered off over the next 5 days, the abnormal movements improved and then ceased 5 days after complete discontinuation of the drug. Notably, pregabalin was reintroduced at the time of felbamate discontinuation. A significant improvement in tonic seizures was also seen in the week after felbamate discontinuation and pregabalin reinitiation. Conclusions: Emergence of involuntary movements is a rare complication of antiepileptic drugs. To our knowledge, only two cases of felbamate-induced abnormal movements (one with choreoathetosis and one with acute dystonic reaction) have been described in the literature thusfar. The exact mechanism and neurotransmitter involvement of AED-induced involuntary movements is unknown. Antiparkinsonian benefits have been previously ascribed to felbamate, related to inhibition of the N-methyl-D-aspartate (NMDA) receptor. Specifically, felbamate's ability to block the glycine-binding sites of the NMDA receptor complex has been proposed to, in turn, antagonize inhibitory dopaminergic D2 receptor-mediated effects on the indirect striatopallidal pathway. This could theoretically lead to an increase in excessive, involuntary movements. As such, we hypothesize that felbamate toxicity may have led to the development of hyperkinetic movements in our patient due to dysregulation of dopamine signaling in the cortico-basal ganglia circuitry. Funding: None