Journal of Neurology

, Volume 266, Issue 12, pp 3150–3159 | Cite as

Trajectories of brain remodeling in temporal lobe epilepsy

  • Elisabeth Roggenhofer
  • Emiliano Santarnecchi
  • Sandrine Muller
  • Ferath Kherif
  • Roland Wiest
  • Margitta Seeck
  • Bogdan DraganskiEmail author
Original Communication


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.


Temporal 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


Voxel-based morphometry



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.

Author contributions

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.

Supplementary material

415_2019_9546_MOESM1_ESM.docx (21 kb)
Supplementary file1 (DOCX 21 kb)
415_2019_9546_MOESM2_ESM.tif (13.3 mb)
Fig. s1. Structural remodeling in temporal lobe epilepsy subtypes. Statistical parametric maps – SPMs, of between-groups t tests in (A and B) MRI- and (C) MTS TLE in comparison to C, based on VBM whole-brain analysis, displayed on axial T1-weighted image in standard MNI space, at statistical threshold of p<0.001, uncorrected for multiple comparisons. A RED color– increases in volume estimates [for left MRI->C], A-C BLUE color– decreases in left TLE [for C>left MRI- or MTS], B-CGREEN color– decreases in right TLE [for C>right MRI- or MTS]. Abbreviations: TLE – temporal lobe epilepsy, MRI- – MRI negative, MTS – mesial temporal lobe sclerosis, C – healthy controls (TIF 13652 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.LREN, Department for Clinical Neurosciences, CHUVUniversity of LausanneLausanneSwitzerland
  2. 2.Department for Clinical NeurosciencesHUG, University Hospitals and Faculty of MedicineGenevaSwitzerland
  3. 3.Berenson-Allen Center for Non-Invasive Brain Stimulation, Cognitive Neurology Department, Beth Israel Medical CenterHarvard Medical SchoolBostonUSA
  4. 4.Siena Brain Investigation and Neuromodulation Lab, Department of Medicine, Surgery and NeuroscienceUniversity of SienaSienaItaly
  5. 5.Support Center for Advanced Neuroimaging, Institute for Diagnostic and Interventional Neuroradiology, University Hospital InselspitalUniversity of BernBernSwitzerland

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