Regional cortical thickness changes accompanying generalized tonic-clonic seizures

Jennifer A. Ogren; Raghav Tripathi; Paul M. Macey; Rajesh Kumar; John M. Stern; Dawn S. Eliashiv; Luke A. Allen; Beate Diehl; Jerome Engel, Jr; M.R. Sandhya Rani; Samden D. Lhatoo; Ronald M. Harper

NeuroImage: Clinical (Jan 2018)

Regional cortical thickness changes accompanying generalized tonic-clonic seizures

Jennifer A. Ogren,
Raghav Tripathi,
Paul M. Macey,
Rajesh Kumar,
John M. Stern,
Dawn S. Eliashiv,
Luke A. Allen,
Beate Diehl,
Jerome Engel, Jr,
M.R. Sandhya Rani,
Samden D. Lhatoo,
Ronald M. Harper

Affiliations

Jennifer A. Ogren: Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA
Raghav Tripathi: Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA; Case Western Reserve University School of Medicine, Cleveland, OH, USA
Paul M. Macey: UCLA School of Nursing, University of California at Los Angeles, Los Angeles, CA, USA; Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA
Rajesh Kumar: Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA; Department of Anesthesiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA; Department of Radiological Sciences, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA
John M. Stern: Department of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA
Dawn S. Eliashiv: Department of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA
Luke A. Allen: Institute of Neurology, University College London, London, United Kingdom
Beate Diehl: Institute of Neurology, University College London, London, United Kingdom
Jerome Engel, Jr: Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA; Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA
M.R. Sandhya Rani: Epilepsy Center, UH Case Medical Center, Cleveland, OH, USA
Samden D. Lhatoo: Epilepsy Center, UH Case Medical Center, Cleveland, OH, USA
Ronald M. Harper: Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, CA, USA; Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA; Corresponding author at: Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA 90095, USA.

Journal volume & issue: Vol. 20
pp. 205 – 215

Abstract

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Objective: Generalized tonic-clonic seizures are accompanied by cardiovascular and respiratory sequelae that threaten survival. The frequency of these seizures is a major risk factor for sudden unexpected death in epilepsy (SUDEP), a leading cause of untimely death in epilepsy. The circumstances accompanying such fatal events suggest a cardiovascular or respiratory failure induced by unknown neural processes rather than an inherent cardiac or lung deficiency. Certain cortical regions, especially the insular, cingulate, and orbitofrontal cortices, are key structures that integrate sensory input and influence diencephalic and brainstem regions regulating blood pressure, cardiac rhythm, and respiration; output from those cortical regions compromised by epilepsy-associated injury may lead to cardiorespiratory dysregulation. The aim here was to assess changes in cortical integrity, reflected as cortical thickness, relative to healthy controls. Cortical alterations in areas that influence cardiorespiratory action could contribute to SUDEP mechanisms. Methods: High-resolution T1-weighted images were collected with a 3.0-Tesla MRI scanner from 53 patients with generalized tonic-clonic seizures (Mean age ± SD: 37.1 ± 12.6 years, 22 male) at Case Western Reserve University, University College London, and the University of California at Los Angeles. Control data included 530 healthy individuals (37.1 ± 12.6 years; 220 male) from UCLA and two open access databases (OASIS and IXI). Cortical thickness group differences were assessed at all non-cerebellar brain surface locations (P < 0.05 corrected). Results: Increased cortical thickness appeared in post-central gyri, insula, and subgenual, anterior, posterior, and isthmus cingulate cortices. Post-central gyri increases were greater in females, while males showed more extensive cingulate increases. Frontal and temporal cortex, lateral orbitofrontal, frontal pole, and lateral parietal and occipital cortices showed thinning. The extents of thickness changes were sex- and hemisphere-dependent, with only males exhibiting right–sided and posterior cingulate thickening, while females showed only left lateral orbitofrontal thinning. Regional cortical thickness showed modest correlations with seizure frequency, but not epilepsy duration. Significance: Cortical thickening and thinning occur in patients with generalized tonic-clonic seizures, in cardiovascular and somatosensory areas, with extent of changes sex- and hemisphere-dependent. The data show injury in key autonomic and respiratory cortical areas, which may contribute to dysfunctional cardiorespiratory patterns during seizures, as well as to longer-term SUDEP risk. Keywords: Autonomic, Respiratory, Insula, Cingulate, SUDEP

Published in NeuroImage: Clinical

ISSN: 2213-1582 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General): Computer applications to medicine. Medical informatics; Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: http://www.journals.elsevier.com/neuroimage-clinical/

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