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 KM , Balachandra Akshara R , Bartolini Emanuele , Bender Benjamin , Bernasconi Neda , Bernasconi Andrea , Bernhardt Boris , Bargallo Núria , Caldairou Benoit , Caligiuri Maria Eugenia , Carr Sarah JA , 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 Akaria , Keller Simon S , Kochunov Peter V , Kotikalapudi Raviteja , Kreilkamp Barbara AK , Kwan Patrick , Labate Angelo , Langner Soenke , Lenge Matteo , Liu Min , Lui Elaine , Martin Pascal , Mascalchi Mario , Moreira José CV , 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 , Thompson Paul M , Jahanshad Neda , Sisodiya Sanjay M , McDonald Carrie R 
Published: December 2019

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 analyzed from 1,069 non-epileptic controls and 1,249 patients: temporal lobe epilepsy with hippocampal sclerosis (N=599), temporal lobe epilepsy with normal MRI (N=275), genetic generalized epilepsy (N=182) and nonlesional 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 fiber 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<0.001). Across“all epilepsies”lower fractional anisotropy was observed in most fiber tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. Less robust effects were seen with 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. Those 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 differences in fractional anisotropy in the corpus callosum,corona radiataand external capsule, and in mean diffusivity of the anteriorcorona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of microstructural abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibers in a large multicentre study of epilepsy. Overall, epilepsy patients 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 new insights into pathological substrates that may be used to guide future therapeutic and genetic studies.