Abstracts

Rationale: Although corticosteroids and benzodiazepines are effective in reducing spike burden among children with electrical status epilepticus in sleep (ESES) in the setting of Landau Kleffner Syndrome (LKS), encephalopathy with continuous spike-wave in sleep (CSWS), or autistic regression with epileptiform EEG (AREE), many patients either do not respond to therapy, cannot tolerate long-duration therapy, or relapse upon discontinuation of therapy. Given (1) success in the treatment of refractory absence epilepsy with amantadine, (2) the observation that stimulation of brainstem monoaminergic pathways (principally dopaminergic in the case of amantadine) can desynchronize the corticothalamic oscillator (CTO), and (3) the hypothesis that ESES involves recruitment of the CTO, we hypothesized that amantadine might reduce spike burden and improve cognitive function in children with refractory ESES. Methods: We retrospectively identified all patients at UCLA who received amantadine for treatment of video-EEG (VEEG)-confirmed ESES. Clinical and demographic factors were abstracted from the medical record. For each patient, we quantified amantadine exposure with review of all neurology progress notes, and separately tabulated spike-wave index (SWI) on sequential inpatient overnight VEEG studies. Results: We identified 20 patients (6 female) that received amantadine for treatment of ESES. Regarding phenotypic classification, we identified LKS, CSWS, and AREE in 2, 12, and 6 patients, respectively. 16 (80%) suffered comorbid epilepsy, with the discovery of ESES following epilepsy onset by a median of 2.9 years (IQR 1.3, 5.3). At the time of amantadine initiation, median age was 9.0 years (IQR 6.9, 11.2) and patients had failed a median of 4 prior treatments (IQR 3 – 5) for ESES; 19 (95%) and 5 (20%) had failed (or could not tolerate) therapy with benzodiazepines and corticosteroids, respectively. With respect to amantadine exposure, median duration of treatment was 11.5 months (IQR 7.4, 30.1), and median peak dose was 6.4 mg/kg/day (IQR 4.1, 8.8). Parents and/or practitioners reported subjective cognitive and/or behavioral benefit among 11 (55%) patients. Among 17 patients with overnight VEEG before and after amantadine initiation, median percent reduction in SWI was 45.2% (IQR 0, 100), with p = 0.006. Whereas 6 patients had complete resolution of spike-wave, 3 patients exhibited worsening of spike burden. Conclusions: This study suggests that amantadine might be efficacious in the treatment of refractory ESES, with both clinical and electrographic improvement. However, this study is retrospective and lacks several important experimental controls. Future study with a more rigorous experimental design, including standardized and blinded neurocognitive/behavioral assessments, is warranted to verify these findings. Funding: None