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. 2019 Sep 24:10:1025.
doi: 10.3389/fneur.2019.01025. eCollection 2019.

Gene-Related Cerebellar Neurodegeneration in SCA3/MJD: A Case-Controlled Imaging-Genetic Study

Huirong Peng  1 , Xiaochun Liang  1 , Zhe Long  2 , Zhao Chen  1 , Yuting Shi  1 , Kun Xia  3 , Li Meng  4 , Beisha Tang  1   3   5   6   7   8   9 , Rong Qiu  10 , Hong Jiang  1   3   5   6   11
Affiliations

Gene-Related Cerebellar Neurodegeneration in SCA3/MJD: A Case-Controlled Imaging-Genetic Study

Huirong Peng et al. Front Neurol. .

Erratum in

Abstract

Background: Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is one of the nine polyglutamine (polyQ) diseases and is caused by a CAG repeat expansion within the coding sequence of the ATXN3 gene. Few multimodal imaging analyses of the macro- and micro-structural changes have been performed. Methods: In the present study, we recruited 31 genetically-confirmed symptomatic SCA3/MJD patients and 31 healthy subjects as controls for a multimodal neuroimaging study using structural magnetic resonance imaging (sMRI), proton magnetic resonance spectroscopy (1H-MRS) and diffusion tensor imaging (DTI). Results: The SCA3/MJD patients displayed a significantly reduced of gray matter volume in the cerebellum, pons, midbrain and medulla, as well as inferior frontal gyrus and insula, and left superior frontal gyrus. The total International Cooperative Ataxia Rating Scale (ICARS) score was inversely correlated with the gray matter volume in the cerebellar culmen, pons and midbrain. The numbers of CAG repeats in the expanded alleles were inversely correlated with the gray matter in the cerebellar culmen. NAA/Cr and NAA/Cho ratio in the middle cerebellar peduncles, dentate nucleus, cerebellar vermis, and thalamus in the SCA3/MJD patients were significantly reduced when compared to that in the normal controls, suggesting neurochemical alterations in cerebellum in the SCA3/MJD patients. Tract-Based Spatial Statistics (TBSS) analysis revealed significant lower volume and mean FA values of the cerebellar peduncles, which inversely correlated with the total scores of ICARS in our patients. Conclusions: In this study, we demonstrated cerebellar degeneration in SCA3/MJD based on tissue volume, neurochemistry, and tissue microstructure. Moreover, the associations between the clinical measures, cerebellar degeneration and genetic variation support a distinct genotype-phenotype relationship in SCA3/MJD.

Keywords: 1HMRS; gray matter; imaging genetics study; spinocerebellar ataxia 3; white matter.

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Figures

Figure 1
Figure 1
Flow-chart of the study. Seventy participants (including 36 SCA3/MJD patients and 34 normal controls) volunteered and were screened for inclusion and exclusion criteria. Five SCA3/MJD patients had to be excluded because they were younger than 18 years old. Three normal controls had to be excluded because they had neurological or psychiatric deficits. Sixty-two participants (including 31 SCA3/MJD patients and 31 normal controls) were enrolled in the study.
Figure 2
Figure 2
The anatomically defined ROIs in the 1HMRS images. 1 = MCP; 2 = dentate nucleus; 3 = cerebellar vermis; 4 = cerebellar cortex; 5 = putamen; 6 = thalamus.
Figure 3
Figure 3
ROIs of the cerebellar peduncles in the color-coded FA maps. The anatomically defined ROIs of the cerebellar peduncles in the color-coded FA maps (superior row) and their resulting fiber tracts (inferior row). SCP, superior cerebellar peduncle; MCP, middle cerebellar peduncle; ICP, inferior cerebellar peduncle.
Figure 4
Figure 4
Reduced white matter volume in the SCA3/MJD patients. Reduced gray matter volume in the SCA3/MJD patients compared with the controls based on voxel-based morphometry (p < 0.05). The color bar refers to the T-values.
Figure 5
Figure 5
Tractography of the cerebellar peduncles. Tractography of the cerebellar peduncles in a control (upper row) and a SCA3/MJD patient (lower row).
See this image and copyright information in PMC

References

    1. Klockgether T, Mariotti CPaulson HL. Spinocerebellar ataxia. Nat Rev Dis Primers. (2019) 5:24. 10.1038/s41572-019-0074-3 - DOI - PubMed
    1. Tang B, Liu C, Shen L, Dai H, Pan Q, Jing L, et al. . Frequency of SCA1, SCA2, SCA3/MJD, SCA6, SCA7, and DRPLA CAG trinucleotide repeat expansion in patients with hereditary spinocerebellar ataxia from Chinese kindreds. Arch Neurol. (2000) 57:540–4. 10.1001/archneur.57.4.540 - DOI - PubMed
    1. Chen Z, Wang P, Wang C, Peng Y, Hou X, Zhou X, et al. . Updated frequency analysis of spinocerebellar ataxia in China. Brain. (2018) 141:e22. 10.1093/brain/awy016 - DOI - PubMed
    1. Jiang H, Tang B, Xia K, Zhou Y, Xu B, Zhao G, et al. . Spinocerebellar ataxia type 6 in Mainland China: molecular and clinical features in four families. J Neurol Sci. (2005) 236:25–9. 10.1016/j.jns.2005.04.009 - DOI - PubMed
    1. Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, et al. . CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet. (1994) 8:221–8. 10.1038/ng1194-221 - DOI - PubMed

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