White Matter Damage and Myelin Loss in Rare PolyG Diseases: A 3T MRI Pilot Study

Motivation: Literature suggests that white matter (WM) may be specifically affected in polyG diseases, a novel class of genetic neurodegenerative diseases including fragile X-associated tremor/ataxia syndrome (FXTAS) and neuronal intranuclear inclusion disease (NIID). Goal(s): To use advanced MRI to characterize WM in polyG disease. Approach: 3T myelin water imaging and diffusion tensor imaging in participants with FXTAS and NIID. Results: FXTAS and NIID demonstrated diffuse cerebral WM damage and myelin loss. Middle cerebellar peduncle (MCP) changes were seen in FXTAS, but not in NIID. Diffusion hyperintense foci in the MCP (FXTAS) and frontal WM (FXTAS and NIID) matched foci of highest dysmyelination. Impact: Fragile X-associated tremor/ataxia syndrome and neuronal intranuclear inclusion disease show diffuse cerebral white matter abnormalities and myelin damage, and spatially differential changes in the frontal white matter and middle cerebellar peduncle.