White matter abnormalities across different epilepsy syndromes in adults: an ENIGMA-Epilepsy study

Abstract

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 < 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.

Mosaic trisomy of chromosome 1q in human brain tissue associates with unilateral polymicrogyria, very early-onset focal epilepsy, and severe developmental delay

“…Our results are in line with a recently published international consensus recommendation on the diagnostic work-up for MCD [ 59 ]. This expert panel recognized PMG as one of the most frequent and most heterogeneous malformations in etiology with currently only 9–20% of cases yielding a (blood-based) molecular diagnosis.…”

Functional and microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19

“…We acquired all images (patients and controls) in a 3T Philips Achieva scanner using the same protocols: i) structural 3D T1-weighted images with isotropic voxel (1×1×1 mm 3 ), acquired in the sagittal plane with 180 slices, TE = 3.2 ms, TR = 7 ms, matrix = 240×240, flip angle = 8 and FOV = 240×240mm2) ii) Resting-state: echo planar functional images with isotropic voxel (3×3×3 mm 3 ), acquired on the axial plane with 40 slices, no gap, matrix of 80×80, flip angle = 90°, FOV = 240×240mm 2 , TR=2s, TE=30ms and 180 dynamics, resulting in a six minutes scan; iii) DTI was acquired with a single-shot EPI technique (voxel size = 2×2×2 mm 3 , 32 gradient directions, max b-factor = 1000 s/mm 2 , FOV = 256×256 mm 2 )(Garcia et al, 2019; Hatton et al, 2020). Additional details of MRI protocol acquisitions for post-COVID individuals are presented in the supplementary file.…”

Epilepsy as a Disease of White Matter

“…More recent neuroimaging studies definitively confirm involvement of white matter in patients with epilepsy. 5 , 6 The introductory text by Hatton et al 7 nicely summarizes previous studies about white matter changes in epilepsy, which document white matter changes in patients with temporal lobe epilepsy (TLE) and genetic generalized epilepsy (GGE). White matter changes also correlate with cognitive changes as well as postoperative seizure outcomes in people with long-standing epilepsy.…”