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

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 ?4 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 ?4 allelic frequencies between MTLE-HS patients and controls or between MTLE-HS subgroups were observed. Nevertheless, ApoE ?4 carriers had an earlier MTLE-HS onset (11.0 ± 7.9 years in ApoE ?4 carriers vs. 14.4 ± 11.2 years in ApoE ?4 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 ?4 and FS may not participate directly in etiopathogenic mechanisms of MTLE-HS but could hasten the disease development in predisposed individuals.