Abstracts

Rationale: Angelman Syndrome (AS) is a neurodevelopmental genetic condition characterized by developmental delay, severe speech impairment, movement or balance disorders, and behavioral uniqueness, predominantly caused by chromosome 15 irregularities. Epilepsy is present in over 80% of affected individuals and is often refractory to anti-seizure medications (ASM). Despite the high prevalence of seizures in AS, as well as their pharmaco-resistance (combination therapy between 47-60%), the literature provides minimal evidence for ASM-efficacy. However, valproic acid (VPA) continues to be the most commonly prescribed ASM in AS, and there is minimal evidence regarding newer ASMs in this disorder. This case report describes the dramatic seizure-response to levetiracetam (LEV) in a child with AS (who previously failed VPA), and reviews the scant literature related to similar cases. Methods: Case report with literature review. Fluorescent in-situ hybridization (FISH), Electroencephalography (EEG). Results: A 3-year-old boy with AS, confirmed by genetic testing (FISH) at age 22 months, presented with frequent seizures at age 33 months. Initial EEG was unobtainable and VPA was introduced (20mg/kg/d), reaching a therapeutic dose (30mg/kg/d) within 2 weeks, but without significant seizure-response. Hence, VPA-titration continued up to 55mg/kg/d with only partial seizure-control while the patient gradually became encephalopathic (VPA-encephalopathy). Concomitant EEG results revealed paroxysmal occipital spike-and-slow waves/notched-delta activity, and very frequent runs of high-voltage generalized slow repetitive sharp-and-slow wave complexes in association with impairment of consciousness and blepharoptosis, during wakefulness. The combination of poor seizure-control with development of VPA-encephalopathy lead to VPA discontinuation. LEV was simultaneously introduced and titrated up to 40mg/kg with significant seizure-response (>50%) within 1 week. As LEV continued up to 60mg/kg, complete seizure-control was achieved. Nine months after LEV was initiated, the EEG showed no interictal epileptiform activity in wakefulness, and very frequent asynchronous occipital spikes, and runs of fast repetitive bi-occipital sharp-and-slow waves, in sleep. Fourteen months following LEV-commencement, the child remains seizure-free and his developmental progress has resumed at a remarkable pace. Review of the literature regarding treatment of epilepsy in AS showed only one (questionnaire-based) study which assessed the use of ASMs in AS, and it confirmed the lack of evidenced-based data for its use. Conclusions: - There are minimal studies documenting the use of newer ASMs in AS. - Newer ASMs may be both efficacious and associated with a more favorable side-effect profile in patients with AS. - LEV may be a valid mono- or combination therapy in AS. - Further studies are needed to evaluate the use of newer ASMs in AS; such studies would be especially useful if done in combination with genetic sub-typing analyses.