Amantadine: A new treatment for refractory electrical status epilepticus in sleep

Epilepsy Behav. 2018 Jul:84:74-78. doi: 10.1016/j.yebeh.2018.04.018. Epub 2018 May 10.

Abstract

Purpose: Electrical status epilepticus in sleep (ESES) is an electrographic abnormality linked to language abnormalities and cognitive dysfunction and specifically associated with Landau-Kleffner syndrome (LKS), the syndrome of continuous spike and wave in slow-wave sleep (CSWS), and autistic regression with epileptiform EEG (AREE). As first-line therapies for treatment of ESES display inadequate efficacy and confer substantial risk, we set out to describe our center's experience with amantadine in the treatment of ESES.

Methods: Patients with video-EEG-confirmed ESES who received amantadine were retrospectively identified in a clinical EEG database. Spike-wave index, before and after amantadine exposure, was compared in a pairwise fashion. In an exploratory analysis, we cataloged reported changes in language functioning, cognition, and autistic features, which accompanied treatment.

Results: We identified 20 patients with ESES-associated syndromes. Median cumulative weighted average amantadine dosage was 2.1 mg/kg/d (interquartile range (IQR): 1.1, 4.5), and median duration of therapy was 11.5 months (IQR: 7.8, 26.6). In comparison with median baseline spike-wave index (76%), post-amantadine spike-wave index (53%) was reduced, with P = 0.01. Six (30%) patients exhibited complete (or nearly complete) resolution of ESES. A majority of patients exhibited subjective cognitive, linguistic, or behavioral benefit. Amantadine was generally well-tolerated despite substantial dosage and duration of therapy.

Conclusions: This study suggests that amantadine may be effective in the treatment of ESES-associated syndromes but warrants replication in a more rigorous study.

Keywords: Autism; Benzodiazepine; Corticosteroid; EEG; ESES; Epileptic encephalopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amantadine / administration & dosage
  • Amantadine / therapeutic use*
  • Autistic Disorder / complications
  • Autistic Disorder / drug therapy
  • Autistic Disorder / physiopathology
  • Child
  • Child, Preschool
  • Cognition / drug effects
  • Cognitive Dysfunction / complications
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / physiopathology
  • Dopamine Agents / administration & dosage
  • Dopamine Agents / therapeutic use*
  • Electroencephalography
  • Female
  • Humans
  • Landau-Kleffner Syndrome / complications
  • Landau-Kleffner Syndrome / physiopathology
  • Language*
  • Male
  • Retrospective Studies
  • Sleep / drug effects*
  • Sleep / physiology
  • Status Epilepticus / complications
  • Status Epilepticus / drug therapy*
  • Status Epilepticus / physiopathology
  • Treatment Outcome

Substances

  • Dopamine Agents
  • Amantadine