White matter abnormalities across different epilepsy syndromes in adults: an ENIGMA-Epilepsy study
Authors: Hatton Sean N , Huynh Khoa H , Bonilha Leonardo , Abela Eugenio , Alhusaini Saud , Altmann Andre , Alvim Marina K M , Balachandra Akshara R , Bartolini Emanuele , Bender Benjamin , Bernasconi Neda , Bernasconi Andrea , Bernhardt Boris , Bargallo Núria , Caldairou Benoit , Caligiuri Maria E , Carr Sarah J A , Cavalleri Gianpiero L , Cendes Fernando , Concha Luis , Davoodi-bojd Esmaeil , Desmond Patricia M , Devinsky Orrin , Doherty Colin P , Domin Martin , Duncan John S , Focke Niels K , Foley Sonya F , Gambardella Antonio , Gleichgerrcht Ezequiel , Guerrini Renzo , Hamandi Khalid , Ishikawa Akari , Keller Simon S , Kochunov Peter V , Kotikalapudi Raviteja , Kreilkamp Barbara A K , Kwan Patrick , Labate Angelo , Langner Soenke , Lenge Matteo , Liu Min , Lui Elaine , Martin Pascal , Mascalchi Mario , Moreira José C V , Morita-Sherman Marcia E , O’Brien Terence J , Pardoe Heath R , Pariente José C , Ribeiro Letícia F , Richardson Mark P , Rocha Cristiane S , Rodríguez-Cruces Raúl , Rosenow Felix , Severino Mariasavina , Sinclair Benjamin , Soltanian-Zadeh Hamid , Striano Pasquale , Taylor Peter N , Thomas Rhys H , Tortora Domenico , Velakoulis Dennis , Vezzani Annamaria , Vivash Lucy , von Podewils Felix , Vos Sjoerd B , Weber Bernd , Winston Gavin P , Yasuda Clarissa L , Zhu Alyssa H , Thompson Paul M , Whelan Christopher D , Jahanshad Neda , Sisodiya Sanjay M , McDonald Carrie R 
Published: June 2020

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P &lt; 0.001). Across ‘all epilepsies’ lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research.