Brain structure and organization five decades after childhood onset epilepsy

Abstract

The purpose of this project was to characterize brain structure and organization in persons with active and remitted childhood onset epilepsy 50 years after diagnosis compared to healthy controls. Participants from a population-based investigation of uncomplicated childhood onset epilepsy were followed up 5 decades later. Forty-one participants had a history of childhood onset epilepsy (mean age of onset= 5.2 yrs, current chronological age= 56.0 yrs) and were compared to 48 population-based controls (mean age= 55.9 yrs). Of the epilepsy participants, 8 had persisting active epilepsy and in 33 the epilepsy had remitted. All participants underwent 3T MRI with subsequent vertex analysis of cortical volume, thickness, surface area and gyral complexity. In addition, cortical and subcortical volumes, including regions of the frontal, parietal, temporal, and occipital lobes, and subcortical structures including amygdala, thalamus, and hippocampus, were analyzed using graph theory techniques. There were modest group differences in traditional vertex-based analyses of cortical volume, thickness, surface area and gyral index, as well as across volumes of subcortical structures, after correction for multiple comparisons. Graph theory analyses revealed suboptimal topological structural organization with enhanced network segregation and reduced global integration in the epilepsy participants compared to controls, these patterns significantly more extreme in the active epilepsy group. Furthermore, both groups with epilepsy presented a greater number of higher Z-score regions in betweenness centrality (BC) than lower Z-score regions compared to controls. Also, contrary to the group with remitted epilepsy, patients with active epilepsy presented most of their high BC Z-score regions in subcortical areas including the amygdala, thalamus, hippocampus, pallidum and accumbens. Overall, this population-based investigation of long term outcome (5 decades) of childhood onset epilepsy reveals persisting abnormalities, especially when examined by graph theoretical measurements, and provides new insights into the very long term outcomes of active and remitted epilepsy.

Network, clinical and sociodemographic features of cognitive phenotypes in temporal lobe epilepsy

“…Although regional and network-based analyses were performed using the same morphological data (i.e., volumetric data), the nature of graph theory analyses provided another view of morphometric data that rendered additional insights regarding how the cognitive phenotypes differed in their morphological associations. This same pattern was observed in a cohort of patients with uncomplicated childhood onset epilepsies 50 years after their diagnosis ( Garcia-Ramos et al, 2017 ), where graph theory analyses of the morphological networks revealed subtleties missed by conventional regional analyses. Further, Reyes et al (2019) recently demonstrated that TLE patients with an isolated language impairment showed unremarkable regional analyses but differences in network structure using graph theory analysis ( Reyes et al, 2019 ).…”

A Purinergic P2 Receptor Family-Mediated Increase in Thrombospondin-1 Bolsters Synaptic Density and Epileptic Seizure Activity in the Amygdala-Kindling Rat Model

“…Epileptic activity can induce excitotoxic damage locally, but it can also propagate through white matter tracts and damage distant areas, including areas that are contralateral to the focus (Feldt Muldoon et al, 2013 ; Burns et al, 2014 ; Caciagli et al, 2014 ; Xu et al, 2014 ). For example, complex partial seizures in patients with epilepsy were found to begin at abnormal hippocampal synapses in the middle temporal lobe (Colder et al, 1996 ) and were found to propagate through the hippocampal network to cause temporal lobe epilepsy (Garcia-Ramos et al, 2017 ; Lupica et al, 2017 ). This propagation can cause a pathological restructuring of the affected networks by increasing synaptogenesis that facilitates the development and spread of seizure activity (Fidzinski et al, 2015 ; Heller and Rusakov, 2015 ; Amakhin et al, 2016 ).…”

Obsessive-compulsive symptoms and resting-state functional characteristics in pre-adolescent children from the general population

“…Comparative studies between structural and functional connectivity have produced mixed results and demonstrate imperfect correspondence: at best half of the variance in functional connections is explained by structure (Suárez et al, 2020 ). In the literature, co-occurring alterations in thalamus morphometry and network topology have only been reported in epilepsy (Garcia-Ramos et al, 2017 ; Lee et al, 2020 ).…”