Epilepsy and respiratory chain defects in children with mitochondrial encephalopathies

Neuropediatrics. 2008 Feb;39(1):8-13. doi: 10.1055/s-2008-1076737.

Abstract

Objective: The purpose of this study was to determine the relationship between epilepsy and respiratory chain defects in children with mitochondrial encephalopathies (ME).

Study design: We conducted a retrospective review of the medical records of children referred for evaluation of an ME. Only patients assigned a definite diagnosis of ME using modified Walker criteria and with a respiratory chain defect were included. Clinical data pertaining to the ME and epilepsy type were collected. Mitochondria were isolated by subcellular fractionation from a vastus lateralis muscle biopsy and studies were performed using polarographic and spectroscopic techniques for the quantitative determination of NADH and cytochrome components of the respiratory chain.

Results: A total of 38 children with ME were identified. Seizures were present in 61%. Sixteen of 23 children with epilepsy (70%) had refractory epilepsy associated with a progressive encephalopathy. Children with epilepsy had a significantly higher incidence of complex I defects than children without epilepsy (p<0.01). Complex III and IV defects were significantly higher in patients without epilepsy (p<0.01 and p<0.05, respectively) than in those with epilepsy.

Conclusions: Epilepsy is an important component of ME. The higher incidence of complex I defects in patients with epilepsy suggests a possible relationship between mitochondrial oxidative stress dysfunction and epileptogenic process.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cytochromes / metabolism
  • Electroencephalography / methods
  • Electron Transport
  • Electron Transport Complex I / metabolism
  • Electron Transport Complex III / metabolism
  • Electron Transport Complex IV / metabolism
  • Epilepsy / complications
  • Epilepsy / pathology*
  • Epilepsy / physiopathology
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mitochondria, Muscle / metabolism*
  • Mitochondrial Encephalomyopathies / complications
  • Mitochondrial Encephalomyopathies / metabolism
  • Mitochondrial Encephalomyopathies / physiopathology*
  • NAD / metabolism
  • Oxidative Stress
  • Retrospective Studies

Substances

  • Cytochromes
  • NAD
  • Electron Transport Complex IV
  • Electron Transport Complex I
  • Electron Transport Complex III