White matter abnormalities at a regional and voxel level in focal and generalized epilepsy: A systematic review and meta-analysis

Objective Since the introduction of diffusion tensor imaging, white matter abnormalities in epilepsy have been studied extensively. However, the affected areas reported, the extent of abnormalities and the association with relevant clinical parameters are highly variable. We aimed to obtain a more consistent estimate of white matter abnormalities and their association with clinical parameters in different epilepsy types. Methods We systematically searched for differences in white matter fractional anisotropy and mean diffusivity, at regional and voxel level, between people with epilepsy and healthy controls. Meta-analyses were used to quantify the directionality and extent of these differences. Correlations between white matter differences and age of epilepsy onset, duration of epilepsy and sex were assessed with meta-regressions. Results Forty-two studies, with 1027 people with epilepsy and 1122 controls, were included with regional data. Sixteen voxel-based studies were also included. People with temporal or frontal lobe epilepsy had significantly decreased fractional anisotropy (Δ –0.021, 95% confidence interval –0.026 to –0.016) and increased mean diffusivity (Δ0.026 × 10^–3 mm²/s, 0.012 to 0.039) in the commissural, association and projection white matter fibers. White matter was much less affected in generalized epilepsy. White matter changes in people with focal epilepsy correlated with age at onset, epilepsy duration and sex. Significance This study provides a better estimation of white matter changes in different epilepsies. Effects are particularly found in people with focal epilepsy. Correlations with the duration of focal epilepsy support the hypothesis that these changes are, at least partly, a consequence of seizures and may warrant early surgery. Future studies need to guarantee adequate group sizes, as white matter differences in epilepsy are small.