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Widespread cortical dyslamination in epilepsy patients with malformations of cortical development

  • Functional Neuroradiology
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Abstract

Purpose

Recent research in epilepsy patients confirms our understanding of epilepsy as a network disorder with widespread cortical compromise. Here, we aimed to investigate the neocortical laminar architecture in patients with focal cortical dysplasia (FCD) and periventricular nodular heterotopia (PNH) using clinically feasible 3 T MRI.

Methods

Eighteen epilepsy patients (FCD and PNH groups; n = 9 each) and age-matched healthy controls (n = 9) underwent T1 relaxation 3 T MRI, from which component probability T1 maps were utilized to extract sub-voxel composition of 6 T1 cortical layers. Seventy-eight cortical areas of the automated anatomical labeling atlas were divided into 1000 equal-volume sub-areas for better detection of cortical abnormalities, and logistic regressions were performed to compare FCD/PNH patients with healthy controls with the T1 layers composing each sub-area as regressors. Statistical significance (p < 0.05) was determined by a likelihood-ratio test with correction for false discovery rate using Benjamini-Hochberg method.

Results

Widespread cortical abnormalities were observed in the patient groups. Out of 1000 sub-areas, 291 and 256 bilateral hemispheric cortical sub-areas were found to predict FCD and PNH, respectively. For each of these sub-areas, we were able to identify the T1 layer, which contributed the most to the prediction.

Conclusion

Our results reveal widespread cortical abnormalities in epilepsy patients with FCD and PNH, which may have a role in epileptogenesis, and likely related to recent studies showing widespread structural (e.g., cortical thinning) and diffusion abnormalities in various human epilepsy populations. Our study provides quantitative information of cortical laminar architecture in epilepsy patients that can be further targeted for study in functional and neuropathological studies.

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Data availability

Full anonymized data will be shared at the request from any qualified investigator.

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Funding

This work was performed in partial fulfillment of the requirements for a Ph.D. degree by Eyal Lotan, MD, at the Sackler Faculty of Medicine, Tel Aviv University, Israel. No funding was received for this project.

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Author notes

  1. DT and YA contributed equally to this work.

Authors and Affiliations

  1. Department of Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, 52621, Ramat Gan, Israel

    Eyal Lotan, Ido Tavor, Chen Hoffmann & Galia Tsarfaty

  2. Sackler Faculty of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel

    Eyal Lotan, Ido Tavor, Ilan Blatt, Hadassah Goldberg-Stern, Chen Hoffmann, Galia Tsarfaty & David Tanne

  3. Department of Radiology, NYU Langone Medical Center, 660 1st Ave, New York, NY, 10016, USA

    Eyal Lotan

  4. Sagol School of Neuroscience, Tel Aviv University, 69978, Tel Aviv, Israel

    Omri Tomer & Yaniv Assaf

  5. Department of Neurology, Sheba Medical Center, Tel Hashomer, 52621, Ramat Gan, Israel

    Ilan Blatt

  6. Department of Neurology, Schneider Children’s Medical Center of Israel, 49202, Petah Tikva, Israel

    Hadassah Goldberg-Stern

  7. Stroke Center, Department of Neurology and Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, 52621, Ramat Gan, Israel

    David Tanne

  8. Department of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978, Tel Aviv, Israel

    Yaniv Assaf

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  1. Eyal Lotan
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  2. Omri Tomer
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  3. Ido Tavor
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  7. Galia Tsarfaty
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  9. Yaniv Assaf
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Correspondence to Eyal Lotan.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Ethics Committee of the Sheba Medical Center at Tel-Hashomer, affiliated to Tel-Aviv University (blinded for review).

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Lotan, E., Tomer, O., Tavor, I. et al. Widespread cortical dyslamination in epilepsy patients with malformations of cortical development. Neuroradiology 63, 225–234 (2021). https://doi.org/10.1007/s00234-020-02561-2

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