Diferenças clínicas e de alterações cerebrais estruturais e funcionais entre epilepsias de lobo temporal mesial com e sem sinais de esclerose hipocampal

Author(s)

Ana Carolina Coan

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2013-05-04

Examining board members

Fernando Cendes; Marcondes Cavalcante Franca Junior; Fábio Rogério; Jaderson Costa da Costa; João Pereira Leite

• Advisor: Fernando Cendes

Abstract

Introduction: Mesial temporal lobe epilepsy (MTLE) is not a single disease but a group of different diseases with distinct etiologies that share common clinical and EEG characteristics. Understanding the different types of MTLE is fundamental to the development of more appropriate and individualized therapies for ictal phenomena and comorbidities of each patient. Objective: To evaluate and compare the occurrence of structural and functional abnormalities of MTLE with (MTLE-HS) and without (MTLE-NL) signs of hippocampal sclerosis (HS) in magnetic resonance imaging (MRI) and to correlate these abnormalities with the response to treatment. Methods: Patients diagnosed with MTLE defined by clinical and electroencephalographic, and without structural lesions except for signs of HS were evaluated with clinical data and structural and functional 3T MRIs. Patients were classified as MTLE with (MTLE-HS) or without (TLE-NL) signs of HS by quantifying and hippocampal volume and signal. Amygdala volume quantification was also performed. Analysis of volume of brain gray matter (GM) of both groups was performed using the technique of voxel-based morphometry (VBM). Analysis of functional changes related to interictal epileptic discharges (IED) in both groups was performed with concomitant use of EEG and functional MRI (EEG-fMRI). Results: The quantification of volume and hippocampal signal in MRI scans of 203 patients with MTLE increased in 28% the sensitivity of detecting signs of HS compared with the visual analysis. Subgroups of patients with MTLE-HS and MTLE-NL and amygdala hypertrophy were observed. After exclusion of patients with undefined or bilateral epileptic focus, a group of 172 patients (122 ELTM-HS and 50 ELTM-NL) were evaluated with VBM technique. Patients with MTLE-NL had higher age of epilepsy onset and shorter duration of epilepsy as well as more frequent family history of epilepsy than patients with MTLE-HS. MTLE-HS and MTLE-NL showed diffuse GM atrophy, including bilateral sensorimotor cortex and thalamus. Different from MTLE-HS group, patients with MTLE-NL showed no atrophy in mesial and neocortical temporal regions and had pronounced atrophy in the orbito-frontal cortex ipsilateral to the epileptic focus. The subdivision of the groups according to the response to antiepileptic drug (AED) revealed diffuse GM atrophy in both benign and refractory and MTLE-HS, despite the second group exhibit more pronounced atrophy specially in areas with no direct connections with the hippocampus. Differently, GM atrophy was observed only in patients with MTLE-NL and refractory seizures. The functional neuronal networks related to IED were different in MTLE-HS and MTLE-NL groups and were distinct from the structural networks detected by VBM technique. Functional analysis revealed in both groups suppression of activity in brain areas compatible with the Default Mode Network (DMN) concomitantly with IED and this pattern was related to better surgical outcome in patients with AED resistant seizures. Conclusion: Structural and functional networks abnormalities are distinct in MTLE-HS and MTLE-NL. Different neural networks are related to surgical and clinical prognosis in MTLE. Detailed knowledge of the neural networks involved in various types of MTLE and the dynamic interaction between them might contribute to improving the treatment of seizures and comorbidities in these patients (AU)