Efficacy of sodium channel blockers in SCN2A early infantile epileptic encephalopathy

Brain Dev. 2017 Apr;39(4):345-348. doi: 10.1016/j.braindev.2016.10.015. Epub 2016 Nov 19.

Abstract

Background: Recent clinical evidence supports a targeted therapeutic approach for genetic epileptic encephalopathies based on the molecular dysfunction.

Patient description: A 2-day-old male infant presented with epileptic encephalopathy characterized by burst-suppression EEG background and tonic-clonic migrating partial seizures. The condition was refractory to phenobarbital, pyridoxine, pyridoxal phosphate and levetiracetam, but a dramatic response to an intravenous loading dose of phenytoin was documented by video-EEG monitoring. Over weeks phenytoin was successfully switched to carbamazepine to prevent seizure relapses associated with difficulty in maintaining proper blood levels of phenytoin. Genetic analysis identified a novel de novo heterozygous mutation (c.[4633A>G]p.[Met1545Val]) in SCN2A. At two years and three months of age the patient is still seizure-free on carbamazepine, although a developmental delay is evident.

Conclusions: Sodium channel blockers represent the first-line treatment for confirmed or suspected SCN2A-related epileptic encephalopathies. In severe cases with compatible electro-clinical features we propose a treatment algorithm based on a test trial with high dose intravenous phenytoin followed in case of a positive response by carbamazepine, more suitable for long-term maintenance treatment. Because of their rarity, collaborative studies are needed to delineate shared therapeutic protocols for EIEE based on the electro-clinical features and the presumed underlying genetic substrate.

Keywords: Carbamazepine; Early infantile epileptic encephalopathy; Phenytoin; SCN2A; Sodium channel blockers.

Publication types

  • Case Reports

MeSH terms

  • Anticonvulsants / therapeutic use
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Brain / physiopathology
  • Carbamazepine / therapeutic use*
  • Dose-Response Relationship, Drug
  • Humans
  • Infant, Newborn
  • Male
  • NAV1.2 Voltage-Gated Sodium Channel / genetics*
  • Phenytoin / therapeutic use*
  • Sodium Channel Blockers / therapeutic use*
  • Spasms, Infantile / diagnostic imaging
  • Spasms, Infantile / drug therapy*
  • Spasms, Infantile / genetics*
  • Spasms, Infantile / physiopathology
  • Treatment Outcome

Substances

  • Anticonvulsants
  • NAV1.2 Voltage-Gated Sodium Channel
  • SCN2A protein, human
  • Sodium Channel Blockers
  • Carbamazepine
  • Phenytoin

Supplementary concepts

  • Infantile Epileptic-Dyskinetic Encephalopathy