Mitochondrial respiratory chain defects: underlying etiology in various epileptic conditions

Epilepsia. 2008 Apr;49(4):685-90. doi: 10.1111/j.1528-1167.2007.01522.x. Epub 2008 Feb 5.

Abstract

Purpose: To determine if defects in mitochondrial respiratory chain enzyme complexes (MRCs) contribute to the etiology of childhood epilepsy.

Methods: We reviewed the clinical and laboratory features of 48 epileptic patients (23 male, 25 female) with MRC defects that were confirmed by biochemical assays using muscle biopsies.

Results: (1) Thirty-five cases (72.9%) were MRC I deficient, one case (2.1%) was MRC II deficient, 11 cases (22.9%) were MRC IV deficient, and one case (2.1%) had combined MRC I and IV deficiencies. (2) In our clinical diagnosis, there were 10 cases (20.8%) with Leigh disease and one case each with myopathy, encephalopathy, lactic acidosis, stroke-like episodes (MELAS) or Alpers' disease (2.1%). Most of the remaining cases (75.0%) had uncategorized mitochondrial cytopathy with nonspecific encephalopathy. (3) For epileptic classification, there were two cases (4.2%) of Ohtahara syndrome, 10 cases (20.8%) of West syndrome, 12 cases (25.0%) of Lennox-Gastaut syndrome, two cases (4.2%) of Landau-Kleffner syndrome, 14 cases (29.2%) of generalized epilepsy, and eight cases (16.7%) of partial epilepsy. (4) The mean age of seizure onset was 2.68 +/- 2.21 (range: 1 month - 5.5 years). (5) Magnetic resonance imaging (MRI) showed diffuse cortical atrophy in 34 cases (70.8%), basal ganglia signal changes in 18 cases (37.5%) and thalamus signal changes in 12 cases (25.0%). (6) A ketogenic diet produced clinical improvements, including seizure reduction and global functional improvement in 75% of 24 patients.

Conclusions: MRC defects are one of the important causes of probably symptomatic childhood epilepsy. A ketogenic diet should be carefully considered for treatment of intractable epilepsy related to MRC defects.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Lactic / diagnosis
  • Age Factors
  • Age of Onset
  • Anticonvulsants / therapeutic use
  • Atrophy
  • Brain / pathology
  • Child
  • Child, Preschool
  • Drug Resistance
  • Electroencephalography / statistics & numerical data
  • Epilepsy / diagnosis
  • Epilepsy / diet therapy
  • Epilepsy / etiology*
  • Female
  • Humans
  • Ketosis / metabolism
  • Magnetic Resonance Imaging / statistics & numerical data
  • Magnetic Resonance Spectroscopy
  • Male
  • Mitochondrial Diseases / complications*
  • Mitochondrial Diseases / diagnosis
  • Mitochondrial Diseases / pathology
  • Muscle, Skeletal / pathology

Substances

  • Anticonvulsants