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Trajectories of brain remodeling in temporal lobe epilepsy

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Abstract

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.

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Abbreviations

AO:

Age of disease onset

FS:

Frequency of seizures

FWE:

Family-wise error correction

MRI−:

MRI negative temporal lobe epilepsy

MTS:

Mesial temporal lobe sclerosis

ROI:

Region-of-interest

SPM:

Statistical parametric mapping

TD:

Time duration of disease

TIV:

Total intracranial volume

TLE:

Medial temporal lobe epilepsy

VBM:

Voxel-based morphometry

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Acknowledgements

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.

Funding

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.

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Author notes

  1. Elisabeth Roggenhofer and Emiliano Santarnecchi shared the first authorship.

Authors and Affiliations

  1. LREN, Department for Clinical Neurosciences, CHUV, University of Lausanne, Mont Paisible 16, 1011, Lausanne, Switzerland

    Elisabeth Roggenhofer, Sandrine Muller, Ferath Kherif & Bogdan Draganski

  2. Department for Clinical Neurosciences, HUG, University Hospitals and Faculty of Medicine, Geneva, Switzerland

    Elisabeth Roggenhofer & Margitta Seeck

  3. Berenson-Allen Center for Non-Invasive Brain Stimulation, Cognitive Neurology Department, Beth Israel Medical Center, Harvard Medical School, Boston, MA, USA

    Emiliano Santarnecchi

  4. Siena Brain Investigation and Neuromodulation Lab, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy

    Emiliano Santarnecchi

  5. Support Center for Advanced Neuroimaging, Institute for Diagnostic and Interventional Neuroradiology, University Hospital Inselspital, University of Bern, Bern, Switzerland

    Roland Wiest

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  1. Elisabeth Roggenhofer
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  2. Emiliano Santarnecchi
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  3. Sandrine Muller
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  4. Ferath Kherif
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  5. Roland Wiest
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  6. Margitta Seeck
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  7. Bogdan Draganski
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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.

Corresponding author

Correspondence to Bogdan Draganski.

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Supplementary file1 (DOCX 21 kb)

415_2019_9546_MOESM2_ESM.tif

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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Roggenhofer, E., Santarnecchi, E., Muller, S. et al. Trajectories of brain remodeling in temporal lobe epilepsy. J Neurol 266, 3150–3159 (2019). https://doi.org/10.1007/s00415-019-09546-z

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  • DOI: https://doi.org/10.1007/s00415-019-09546-z

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