Trajectories of brain remodeling in temporal lobe epilepsy
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Temporal lobe epilepsy has been usually associated with progressive brain atrophy due to neuronal cell loss. However, recent animal models demonstrated a dual effect of epileptic seizures with initial enhancement of hippocampal neurogenesis followed by abnormal astrocyte proliferation and neurogenesis depletion in the chronic stage. Our aim was to test for the hypothesized bidirectional pattern of epilepsy-associated brain remodeling in the context of the presence and absence of mesial temporal lobe sclerosis. We acquired MRIs from a large cohort of mesial temporal lobe epilepsy patients with or without hippocampus sclerosis on radiological examination. The statistical analysis tested explicitly for common and differential brain patterns between the two patients’ cohorts and healthy controls within the computational anatomy framework of voxel-based morphometry. The main effect of disease was associated with continuous hippocampus volume loss ipsilateral to the seizure onset zone in both temporal lobe epilepsy cohorts. The post hoc simple effects tests demonstrated bilateral hippocampus volume increase in the early epilepsy stages in patients without hippocampus sclerosis. Early age of onset and longer disease duration correlated with volume decrease in the ipsilateral hippocampus. Our findings of seizure-induced hippocampal remodeling are associated with specific patterns of mesial temporal lobe atrophy that are modulated by individual clinical phenotype features. Directionality of hippocampus volume changes strongly depends on the chronicity of disease. Specific anatomy differences represent a snapshot within a progressive continuum of seizure-induced structural remodeling.
KeywordsTemporal lobe epilepsy Magnetic resonance imaging Computational anatomy Voxel-based morphometry Brain plasticity Hippocampus Medial temporal lobe
Age of disease onset
Frequency of seizures
Family-wise error correction
MRI negative temporal lobe epilepsy
Mesial temporal lobe sclerosis
Statistical parametric mapping
Time duration of disease
Total intracranial volume
Medial temporal lobe epilepsy
We would like to thank the participants for their beneficial contribution to the study and Lester Melie-Garcia for support on preprocessing of structural MRI data.
ER, ES, RW, MS and BD were involved in conception of the project. ER and BD were involved in design of the study. ES and GV were involved in acquisition of data. ER and SM performed imaging preprocessing. ER analyzed the data. ER, FK and BD interpreted the data. ER and BD prepared the manuscript. All the authors reviewed, edited the manuscript and were involved in subsequent revisions.
BD and ER are supported by the Swiss National Science Foundation (NCCR Synapsy, project Grant Nr 32003B_159780 and SPUM 33CM30_140332/1) and the Leenaards Foundation. E. S. was partly supported by the SHARP Grant from the Intelligence Advanced Research Projects Activity (IARPA). The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under Grant agreement no. 604102 (Human Brain Project). LREN is very grateful to the Roger De Spoelberch and Partridge Foundations for their generous financial support.
Compliance with ethical standards
Conflicts of interest
Nothing to report.
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