Progression of gray matter atrophy in seizure‐free patients with temporal lobe epilepsy

Abstract

SUMMARYObjectives: To investigate the presence and progression of gray matter (GM) reduction in seizure-free patients with temporal lobe epilepsy (TLE). Methods: We enrolled 39 consecutive TLE patients, seizure-free for at least 2 years-20 with magnetic resonance imaging (MRI) signs of hippocampal sclerosis (TLE-HS), 19 with normal MRI (TLE-NL), and 74 healthy controls. For longitudinal analysis, we included individuals who had a second MRI with minimum interval of 18 months: 21 patients (10 TLE-HS, 11 TLE-NL) and 11 controls. Three-dimensional (3D) T 1 -weighted images acquired in 3 Tesla MRI were analyzed with voxel-based morphometry (VBM). The images of patients with right-sided interictal epileptogenic zone (EZ) were right-left flipped, as well as a comparable proportion of controls. Cross-sectional analysis: The patients' images from each group were compared to controls to investigate differences in GM volumes. Longitudinal analysis: The first and second images were compared in each group to look for decreased GM volume. Results: Cross-sectional analysis: Patients with TLE-HS had diffuse GM atrophy, including hippocampus and parahippocampal gyrus, insula, frontal, and occipital lobes ipsilateral to EZ, bilateral thalamus and contralateral orbitofrontal gyrus, and caudate. In contrast, TLE-NL group did not present significant differences compared to controls. Longitudinal analysis: TLE-HS presented progressive GM reduction in ipsilateral insula and occipital lobe, contralateral motor area, and bilateral temporal and frontal lobes. TLE-NL had GM progression in ipsilateral hypothalamus and parietal lobe, contralateral cerebellum, and bilateral temporal lobe. Controls did not show changes in GM volume between MRIs. Significance: Diffuse extrahippocampal GM atrophy is present in seizure-free patients with TLE-HS. In addition, there is progressive GM atrophy in patients with and without HS. These results demonstrate that not only ongoing seizures are involved in the progression of GM atrophy. An underlying pathologic mechanism could be responsible for progressive brain volume loss in TLE patients even in seizure-free periods.

Altered structural and functional thalamocortical networks in secondarily generalized extratemporal lobe seizures

“…Labate et al observed GM decreases in the thalami of patients with hippocampal sclerosis and normal MRI with mild TLE (Labate et al, 2008, Labate et al, 2010). In a longitudinal MRI follow-up study of seizure-free TLE patients, Alvim and her colleagues not only found diffuse extrahippocampal GM atrophy but also clarified the progression of the GM atrophy (Alvim et al, 2016). Kim et al found a negative correlation between the disease duration and the thalamocortical FC strength of the bilateral medial prefrontal cortex in patients with IGEs (Kim et al, 2014).…”

Progressive topological disorganization of brain network in focal epilepsy

“…11 This result is in line with a previous study demonstrating the progression of diffuse extrahippocampal gray matter atrophy in temporal lobe epilepsy patients with and without hippocampal sclerosis. 27 Interestingly, we newly found that the characteristic path length was the first network measure of alteration, even in the patients with newly diagnosed epilepsy who were in a drug-naïve state. The characteristic path length is the average shortest path length between all nodes as a measurement of global connectivity and network integration, 2,16 and the mean clustering coefficient measures the connection density in local sub-networks surrounding a given node related to the local network efficiency and segregation, which was decreased in the patients with chronic epilepsy.…”

Impaired vigilance networks in temporal lobe epilepsy: Mechanisms and clinical implications

“…These include problems with executive function, cognitive processing, concentration, and social recognition . Furthermore, mTLE patients demonstrate diffuse neocortical hypometabolism, numerous brain connectivity perturbations, and multifocal gray matter atrophy . In one study using voxel‐based morphometry analysis of serial magnetic resonance imaging (MRI) scans in mTLE patients, gray matter reduction was noted not only in limbic structures, but also in frontal, parietal, and occipital cortices, as well as bilateral thalamus (Figure ) .…”

“…[10][11][12] Furthermore, mTLE patients demonstrate diffuse neocortical hypometabolism, numerous brain connectivity perturbations, and multifocal gray matter atrophy. 3,13,14 In one study using voxel-based morphometry analysis of serial magnetic resonance imaging (MRI) scans in mTLE patients, gray matter reduction was noted not only in limbic structures, but also in frontal, parietal, and occipital cortices, as well as bilateral thalamus (Figure 1). 15 These observations may suggest a common subcortical source (or sources) of widespread network dysfunction in mTLE.…”