Cerebellar White Matter Abnormalities in Patients with Charcot-Marie-Tooth disease

Abstract Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous hereditary peripheral neuropathy. Brain volumetry and diffusion tensor imaging (DTI) were performed in CMT patients with PMP22 duplication, MFN2, GJB1, or NEFL mutations to investigate for structural changes of the cerebellum.Volume in cerebellar white matter (WM) was significantly reduced in CMT patients with NEFL mutations. Abnormal DTI findings ​​were observed in the superior, middle, and inferior cerebellar peduncles predominantly in NEFL mutations, and partly in GJB1 mutations. Cerebellar ataxia was more prevalent in the NEFL mutation (72.7%) than GJB1 mutation (9.1%), but not observed in other genotypic subtypes, which indicates that structural cerebellar abnormalities were associated with the presence of cerebellar ataxia. However, NEFL and GJB1 mutations did not affect cerebellar gray matter (GM), and neither cerebellar GM nor WM abnormalities were observed in PMP22 duplication or MFN2 mutations. We found structural evidence of cerebellar WM abnormalities in CMT patients with NEFL and GJB1 mutations and the association between cerebellar WM involvement and cerebellar ataxia in these genetic subtypes, especially in the NEFL subgroup. Therefore, we suggest that neuroimaging such as MRI volumetry or DTI in CMT patients could play an important role in detecting abnormalities of the cerebellar WM.