Individual fixel-based white matter abnormalities in the epilepsies

Diffusion MRI has provided insight into the widespread structural connectivity changes that characterise the epilepsies. Although syndrome-specific white matter abnormalities have been demonstrated, studies have predominantly relied on statistical comparisons between patient and control groups. For diffusion MRI techniques to be of clinical value, they should be able to detect white matter microstructural changes in individual patients. In this study, we apply an individualised approach to a novel technique known as fixel-based analysis, to examine fibre-tract-specific abnormalities in individuals with epilepsy. We explore the potential clinical value of this individualised fixel-based approach in epilepsy patients with differing syndromic diagnoses. Diffusion MRI data from 90 neurologically healthy control participants and 10 patients with epilepsy (temporal lobe epilepsy, Progressive Myoclonus Epilepsy, Dravet Syndrome, malformations of cortical development) were included in this study. Measures of fibre density and cross-section were extracted for all participants across brain white matter fixels, and mean values computed within select tracts-of-interest. Scanner harmonised and normalised data were then used to compute Z-scores for individual patients with epilepsy. Microstructural white matter abnormalities were observed in distinct patterns in individual patients with epilepsy, both at the tract and fixel level. For patients with specific epilepsy syndromes, the detected white matter abnormalities were largely in line with expected syndrome-specific clinical phenotypes. In patients with lesional epilepsies (e.g., hippocampal sclerosis, periventricular nodular heterotopia, bottom-of-sulcus dysplasia), microstructural abnormalities were concordant with lesion location. This study demonstrates the clinical potential of translating advanced diffusion MRI methodology to individual patient-level use in epilepsy. This technique could be useful both in aiding diagnosis of specific epilepsy syndromes, and in localising structural abnormalities, and is readily amenable to other neurological disorders. We have included code and data for this study, so that individualised white matter changes can be explored robustly in larger cohorts in future work.