title: Age of onset of mesial temporal lobe epilepsy with hippocampal sclerosis: the effect of apolipoprotein E and febrile seizures.
abstract: OBJECTIVE
  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.
authors.affiliation: a Unidade Multidisciplinar de Investigação Biomédica , Instituto Ciências Biomédicas Abel Salazar, Universidade do Porto (UMIB/ICBAS-UP) , Porto , Portugal.|b Laboratório Imunogenética, Departamento de Patologia e Imunologia Molecular , Instituto Ciências Biomédicas Abel Salazar, Universidade do Porto (ICBAS/UP) , Porto , Portugal.
authors.forename: Bárbara
authors.identifier: http://orcid.org/0000-0003-0936-4719
authors.initials: B
authors.lastname: Leal
authors.affiliation: c Departamento de neurociências, Serviço de Neurologia , Hospital de Santo António, Centro Hospitalar do Porto , Porto , Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Chaves
authors.affiliation: a Unidade Multidisciplinar de Investigação Biomédica , Instituto Ciências Biomédicas Abel Salazar, Universidade do Porto (UMIB/ICBAS-UP) , Porto , Portugal.|b Laboratório Imunogenética, Departamento de Patologia e Imunologia Molecular , Instituto Ciências Biomédicas Abel Salazar, Universidade do Porto (ICBAS/UP) , Porto , Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Carvalho
authors.affiliation: a Unidade Multidisciplinar de Investigação Biomédica , Instituto Ciências Biomédicas Abel Salazar, Universidade do Porto (UMIB/ICBAS-UP) , Porto , Portugal.|b Laboratório Imunogenética, Departamento de Patologia e Imunologia Molecular , Instituto Ciências Biomédicas Abel Salazar, Universidade do Porto (ICBAS/UP) , Porto , Portugal.
authors.forename: Andreia
authors.identifier: http://orcid.org/0000-0001-5511-5137
authors.initials: A
authors.lastname: Bettencourt
authors.affiliation: c Departamento de neurociências, Serviço de Neurologia , Hospital de Santo António, Centro Hospitalar do Porto , Porto , Portugal.
authors.forename: Joel
authors.initials: J
authors.lastname: Freitas
authors.affiliation: f Departamento de neurociências, Serviço de Neurofisiologia , Hospital de Santo António, Centro Hospitalar do Porto , Porto , Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Lopes
authors.affiliation: f Departamento de neurociências, Serviço de Neurofisiologia , Hospital de Santo António, Centro Hospitalar do Porto , Porto , Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Ramalheira
authors.affiliation: a Unidade Multidisciplinar de Investigação Biomédica , Instituto Ciências Biomédicas Abel Salazar, Universidade do Porto (UMIB/ICBAS-UP) , Porto , Portugal.|d Departamento de Genética , Instituto Nacional de Saúde Dr. Ricardo Jorge , Porto , Portugal.
authors.forename: Paulo P
authors.identifier: http://orcid.org/0000-0001-6125-7000
authors.initials: PP
authors.lastname: Costa
authors.affiliation: e Departamento do Estudo das Populações , Instituto de Ciências Biomédicas Abel Salazar [ICBAS], Universidade do Porto , Porto , Portugal.
authors.forename: Denisa
authors.identifier: http://orcid.org/0000-0003-4835-8944
authors.initials: D
authors.lastname: Mendonça
authors.affiliation: a Unidade Multidisciplinar de Investigação Biomédica , Instituto Ciências Biomédicas Abel Salazar, Universidade do Porto (UMIB/ICBAS-UP) , Porto , Portugal.|f Departamento de neurociências, Serviço de Neurofisiologia , Hospital de Santo António, Centro Hospitalar do Porto , Porto , Portugal.
authors.forename: António M
authors.identifier: http://orcid.org/0000-0003-1364-5724
authors.initials: AM
authors.lastname: Silva
authors.affiliation: a Unidade Multidisciplinar de Investigação Biomédica , Instituto Ciências Biomédicas Abel Salazar, Universidade do Porto (UMIB/ICBAS-UP) , Porto , Portugal.|b Laboratório Imunogenética, Departamento de Patologia e Imunologia Molecular , Instituto Ciências Biomédicas Abel Salazar, Universidade do Porto (ICBAS/UP) , Porto , Portugal.
authors.forename: Berta M
authors.identifier: http://orcid.org/0000-0001-6579-5068
authors.initials: BM
authors.lastname: Silva
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D053327:Apolipoprotein E4 / Q000235:genetics*; D016022:Case-Control Studies; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000150:complications* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics; D012598:Sclerosis / Q000209:etiology; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4; D020033:Protein Isoforms
keywords: ApoE; Epilepsy; febrile seizures; hippocampus