Brain MRI findings in severe myoclonic epilepsy in infancy and genotype-phenotype correlations

Epilepsia. 2007 Jun;48(6):1092-6. doi: 10.1111/j.1528-1167.2007.01020.x. Epub 2007 Mar 22.

Abstract

Introduction: To determine the occurrence of neuroradiological abnormalities and to perform genotype-phenotype correlations in severe myoclonic epilepsy of infancy (SMEI, Dravet syndrome).

Patients and methods: Alpha-subunit type A of voltage-gated sodium channel (SCN1A) mutational screening was performed by denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation probe amplification (MLPA). MRI inclusion criteria were: last examination obtained after the age of 4 years on 1.5-T systems; hippocampal cuts acquired perpendicular to the long axis of the hippocampus; qualitative assessment was performed on T(1)-weighted, T(2)-weighted, proton density, and 1-3 mm thick coronal FLAIR images.

Results: We collected 58 SMEI patients in whom last MRI was performed at or later than 4 years of age. SCN1A mutations occurred in 35 (60%) cases. Thirteen (22.4%) out of 58 patients showed abnormal MRIs. Eight patients showed cortical brain atrophy of which 3 associated to ventricles abnormalities, 1 to cerebellar atrophy, 1 to white matter hyperintensity; 3 patients had ventricles enlargement only; 1 patient showed hippocampal sclerosis (HS); 1 had focal cortical dysplasia. Genotype-phenotype analysis indicated that abnormal MRIs occurred more frequently in patients without SCN1A mutations (9/23; 39.1%) compared to those carrying SCN1A mutations (4/35; 11.4%) (p=0.02).

Conclusion: Different brain abnormalities may occur in SMEI. Only one case with HS was observed; thus, our study does not support the association between prolonged febrile seizures and HS in SMEI. Abnormal MRIs were significantly more frequent in patients without SCN1A mutations. Prospective MRI studies will assess the etiological role of the changes observed in these patients.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Brain / pathology*
  • Child
  • Child, Preschool
  • Chromatography, High Pressure Liquid*
  • Epilepsies, Myoclonic / diagnosis
  • Epilepsies, Myoclonic / genetics*
  • Epilepsies, Myoclonic / pathology*
  • Female
  • Genotype*
  • Hippocampus / pathology
  • Humans
  • Infant
  • Magnetic Resonance Imaging / statistics & numerical data*
  • Male
  • Mutation / genetics
  • NAV1.1 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins / genetics
  • Phenotype*
  • Retrospective Studies
  • Severity of Illness Index
  • Sodium Channels / genetics*
  • Syndrome

Substances

  • NAV1.1 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins
  • SCN1A protein, human
  • Sodium Channels