Investigation of neuronal auto-antibodies in children diagnosed with epileptic encephalopathy of unknown cause

Brain Dev. 2018 Nov;40(10):909-917. doi: 10.1016/j.braindev.2018.06.002. Epub 2018 Jun 21.

Abstract

Aim: Cryptogenic forms of epileptic encephalopathies (EE) with their well-known features of drug-resistance, mental deterioration and partial response to immunotherapies are ideal candidates for screening for neuronal autoantibodies (NAA).

Method: Fifty consecutive pediatric patients with a diagnosis of EE of unknown cause were included. Nine NAAs were tested by ELISA, RIA or cell-based assays. Clinical features of seronegative and seropositive patients were compared.

Results: NAAs were found in 7/50 (14%) patients. They were N-methyl-d-aspartate receptor in two (4%), glycine receptor in two (4%), contactin-associated protein-like 2 in one (2%), glutamic acid decarboxylase in one (2%) and type A gamma aminobutyric acid receptor in one patient (2%). Furthermore, serum IgGs of two patients negative for well-characterized NAAs, showed strong reactivity with the uncharacterized membrane antigens of live hippocampal neurons. There were no significant differences between seropositive and seronegative patients by means of epilepsy duration, anti-epileptic drug resistance, EE type, types of seizures, seizure frequencies, EEG features or coexisting autoimmune diseases. Some seropositive patients gave good-moderate response to immunotherapy.

Discussion: Potential clues for the possible role of autoimmunity in seropositive patients with EE were atypical prognosis of the classical EE type, atypical progression and unusual neurological findings like dyskinesia.

Keywords: Epileptic encephalopathy; Immune-mediated epilepsy; Lennox-Gastaut syndrome; Neuronal auto-antibodies; West syndrome.

MeSH terms

  • Adolescent
  • Adult
  • Autoantibodies / blood*
  • Child
  • Child, Preschool
  • Epilepsy / blood
  • Epilepsy / diagnosis*
  • Epilepsy / immunology*
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Lennox Gastaut Syndrome / diagnosis
  • Lennox Gastaut Syndrome / immunology
  • Male
  • Membrane Proteins / immunology*
  • Neurons / immunology*
  • Receptors, Neurotransmitter / immunology*
  • Spasms, Infantile / diagnosis
  • Spasms, Infantile / immunology
  • Young Adult

Substances

  • Autoantibodies
  • Membrane Proteins
  • Receptors, Neurotransmitter