Progressive Myoclonus Epilepsy: Distinctive MRI Changes in Cerebellar and Motor Networks

Progressive myoclonus epilepsy (PME) is a rare generalized epilepsy syndrome with a well-characterized genetic basis. The brain networks that are affected to give rise to the distinctive symptoms of PME are less well understood.

Eleven individuals with PME with a confirmed genetic diagnosis and 22 controls were studied. MRI included diffusion acquisition using 64 directions, b = 3000 s/mm². Fixel-based analysis was used to identify white matter pathways with significant abnormality in structural connectivity, with subsequent tract segmentation and analysis. Region-of-interest and whole-brain volumetric analysis of T1-weighted images was performed. The relationship between structural connectivity measures and disease duration, and Unified Myoclonus Rating Scale was assessed.

Analysis of structural connectivity revealed significantly reduced fiber density and fiber bundle cross-section in white matter tracts in individuals with PME, with the most severe involvement of tracts within the cerebello-thalamo-cortical network, particularly the cerebello-thalamic, thalamo-cortical, cortico-thalamic, and corticospinal tracts, as well as the splenium of the corpus callosum. By comparison with these abnormalities, cortico-cortical association pathways were relatively preserved. There was reduced volume in the cerebellum, thalamus, brainstem, and mid-anterior corpus callosum.

Individuals with PME have atrophy and changes in fiber tracts that predominantly affect the cerebello-thalamic and motor systems, likely reflecting neuronal and axonal loss as part of a degenerative process. This imaging pattern is distinctive and accords well with the characteristic clinical, neuropathological, and neurophysiological features of the PMEs. The mechanism by which the PME genes affect these tracts is not yet known.