Age of onset of mesial temporal lobe epilepsy with hippocampal sclerosis: the effect of apolipoprotein E and febrile seizures

Int J Neurosci. 2017 Sep;127(9):800-804. doi: 10.1080/00207454.2016.1264396. Epub 2016 Dec 12.


Purpose: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most frequent pharmaco-resistant epilepsy. It has been associated with febrile seizures (FS) in childhood. Its aetiology remains unclear but genetic factors are involved. Apolipoprotein E (ApoE) is the main lipoprotein secreted in brain. It has a critical immunomodulatory function, influences neurotransmission and it is involved in repairing damaged neurons. ApoE ϵ4 is an isoform of ApoE with altered protein function, previously associated with refractoriness and early onset epilepsy. This study was undertaken to determine if ApoE isoforms are risk factors for MTLE-HS and influence clinical characteristics.

Methods: A group of 188 MTLE-HS patients (101 F, 87 M, mean age = 44.7 ± 11.6 years, 100 with FS antecedents) was studied and compared with a group of 342 healthy individuals in a case-control genetic association study. Data were analysed with Pearson Chi-squared Test or Student's t test, as appropriated.

Results: No differences in ApoE ϵ4 allelic frequencies between MTLE-HS patients and controls or between MTLE-HS subgroups were observed. Nevertheless, ApoE ϵ4 carriers had an earlier MTLE-HS onset (11.0 ± 7.9 years in ApoE ϵ4 carriers vs. 14.4 ± 11.2 years in ApoE ϵ4 non-carriers p < 0.05). Additionally, we observed that MTLE-HS patients with FS antecedents had a statistically significant early disease onset (11.5 ± 8.7 years in FS+ vs. 16.0 ± 12.1 years in FS-, p < 0.01).

Conclusions: Our data show that ApoE ϵ4 and FS may not participate directly in etiopathogenic mechanisms of MTLE-HS but could hasten the disease development in predisposed individuals.

Keywords: ApoE; Epilepsy; febrile seizures; hippocampus.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Apolipoprotein E4 / genetics*
  • Case-Control Studies
  • Electroencephalography
  • Epilepsy, Temporal Lobe / complications*
  • Epilepsy, Temporal Lobe / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Hippocampus / pathology*
  • Humans
  • Male
  • Middle Aged
  • Protein Isoforms / genetics
  • Sclerosis / etiology
  • Statistics, Nonparametric
  • Young Adult


  • Apolipoprotein E4
  • Protein Isoforms