DIFFUSION TENSOR IMAGING ANALYSIS FOR CEREBELLAR WHITE MATTER ABNORMALITIES IN CHARCOT-MARIE-TOOTH DISEASE

Abstract

Introduction: Charcot-Marie-Tooth disease (CMT) is a hereditary peripheral neuropathy with clinical and genetic heterogeneities. Cerebral nervous system (CNS) symptoms have been reported in several CMT subtypes. Diffusion tensor imaging (DTI) study has been widely used in neuroscience field. We employed DTI to assess changes in white matter microstructure by leveraging its sensitivity to diffusion measurement on a microscopic scale.

Methods: We enrolled 94 study participants including 47 healthy controls and 47 CMT patients. Clinical assessments were obtained by detailed history taking and physical examination. Brain volumetry and DTI were performed in 47 CMT patients with PMP22 duplication(n=10), MFN2 (n=15), GJB1 (n=11), or NEFL mutations (n=11)and 47 controls to investigate for structural changes of the cerebellum. We analyzed volumetric and DTI data using the statistical tools.

Results: 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.

Conclusions: Therefore, we suggest that neuroimaging such as MRI volumetry or DTI can be helpful for early detection of cerebellar dysfunction in CMT patients with NEFL and/or GJB1 mutations, especially in cases harboring cerebellar ataxia.