Abstract
Objective
Although previous imaging studies have reported cerebellar gray matter loss in patients with familial cortical myoclonic tremor with epilepsy (FCMTE), the corresponding white matter alterations remain unknown. We investigated white matter structural changes in FCMTE1 and compared them with clinical and electrophysiological features.
Methods
We enrolled 36 patients carrying heterozygous pathogenic intronic pentanucleotide insertions in the SAMD12 gene and 52 age- and sex-matched healthy controls. Diffusion tensor imaging-derived metrics, including fractional anisotropy, mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated along with white matter voxel-based morphometry (VBM) analysis. We also examined correlations between MR metrics and clinical and electrophysiological features.
Results
We detected widespread white matter reductions in MD, RD, and AD values in FCMTE patients, including in the commissural, projection, and association fibers. VBM analysis revealed that increases in white matter volume predominantly occurred in the right cerebellum and sagittal stratum. MD, RD, AD, and VBM analysis clearly indicated changes in the sagittal stratum. We found a positive correlation between VBM values in the right cerebellum and SEP P25–N33 amplitude. Decreased MD and AD values in the right sagittal stratum were detected in patients with versus without photophobia.
Significance
FCMTE is a network disorder involving a wide range of cortical and subcortical structures, including the cerebellum, thalamus, thalamo-cortical connections, and cortico-cortical connections. The right sagittal stratum is closely related with visual symptoms, especially photophobia. Our findings indicate that cerebellum and cortical hyperexcitability are closely linked, and emphasize the important role of the cerebellum in the pathophysiological mechanisms of cortical tremor.
MAR