Cerebellar White Matter Abnormalities in Charcot-Marie-Tooth Disease: A Combined Volumetry and Diffusion Tensor Imaging Analysis.

Sungeun Hwang,Regina Eun-Young Kim,Hyang Woon Lee,Jeong Hyun Yoo,Chang-Hyun Park,Hyeon Jin Kim,Ki Wha Chung,Byung-Ok Choi,Yun Seo Choi,Sol-Ah Kim

doi:10.3390/jcm10214945

Abstract

Charcot–Marie–Tooth disease (CMT) is a genetically heterogeneous hereditary peripheral neuropathy. Brain volumetry and diffusion tensor imaging (DTI) were performed in 47 controls and 47 CMT patients with PMP22 duplication (n = 10), MFN2 (n = 15), GJB1 (n = 11), or NEFL mutations (n = 11) to investigate for structural changes in the cerebellum. Volume of 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 group (72.7%) than the GJB1 mutation group (9.1%) but was 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 the PMP22 duplication or MFN2 mutation groups. We found structural evidence of cerebellar WM abnormalities in CMT patients with NEFL and GJB1 mutations and an 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, for CMT patients could play an important role in detecting abnormalities of cerebellar WM.

Highlights

Charcot–Marie–Tooth disease (CMT) is a hereditary peripheral neuropathy with clinical and genetic heterogeneities [1]
We previously described the diffusion tensor imaging (DTI) abnormality of cerebral white matter (WM) that correlated with clinical disability in CMT patients with mitofusin 2 (MFN2), GJB1, and neurofilament light chain polypeptide (NEFL) mutations [10]
We found structural evidence of cerebellar WM abnormalities, including reduced cerebellar WM by volumetry in the NEFL mutation group and microstructural abnormalities by DTI of the superior cerebellar peduncle (SCP), middle cerebellar peduncle (MCP), and inferior cerebellar peduncle (ICP) in the NEFL and GJB1 subgroups

Summary

Introduction

Charcot–Marie–Tooth disease (CMT) is a hereditary peripheral neuropathy with clinical and genetic heterogeneities [1]. Cerebellar ataxia has been reported in some NEFL patients [6,7,9,10,11]. Even in patients who have been reported to have cerebellar ataxia, it is difficult to detect cerebellar atrophy using routine conventional brain MRI. We previously described the DTI abnormality of cerebral white matter (WM) that correlated with clinical disability in CMT patients with MFN2, GJB1, and NEFL mutations [10]. There has been a report of a combined structural and diffusion MRI study of CMT1A patients [16]. There has been no report of volumetry or DTI studies of the cerebellum in patients with NEFL mutations. We employed DTI to assess changes in white matter microstructure by leveraging its sensitivity to diffusion measurement on a microscopic scale

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Conclusion