CAG repeat length does not associate with the rate of cerebellar degeneration in spinocerebellar ataxia type 3

Shang-Ran Huang; Yu-Te Wu; Chii-Wen Jao; Bing-Wen Soong; Jiing-Feng Lirng; Hsiu-Mei Wu; Po-Shan Wang

doi:10.1016/j.nicl.2016.11.007

CAG repeat length does not associate with the rate of cerebellar degeneration in spinocerebellar ataxia type 3

Neuroimage Clin. 2016 Nov 10:13:97-105. doi: 10.1016/j.nicl.2016.11.007. eCollection 2017.

Authors

Shang-Ran Huang¹, Yu-Te Wu², Chii-Wen Jao³, Bing-Wen Soong⁴, Jiing-Feng Lirng⁵, Hsiu-Mei Wu⁵, Po-Shan Wang⁶

Affiliations

¹ Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No.155, Sec. 2, Linong St., Taipei, Taiwan.
² Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No.155, Sec. 2, Linong St., Taipei, Taiwan; Institute of Biophotonics, National Yang-Ming University, No.155, Sec. 2, Linong St., Taipei, Taiwan.
³ Institute of Biophotonics, National Yang-Ming University, No.155, Sec. 2, Linong St., Taipei, Taiwan.
⁴ Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Rd., Taipei, Taiwan; School of Medicine, National Yang-Ming University, No.155, Sec. 2, Linong St., Taipei, Taiwan.
⁵ School of Medicine, National Yang-Ming University, No.155, Sec. 2, Linong St., Taipei, Taiwan; Department of Radiology, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Rd., Taipei, Taiwan.
⁶ Institute of Biophotonics, National Yang-Ming University, No.155, Sec. 2, Linong St., Taipei, Taiwan; Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Rd., Taipei, Taiwan; School of Medicine, National Yang-Ming University, No.155, Sec. 2, Linong St., Taipei, Taiwan; Department of Neurology, Taipei Municipal Gan-Dau Hospital, No.12, Ln. 225, Zhixing Rd., Taipei, Taiwan.

Abstract

This cross-sectional study investigated the correlation between the CAG repeat length and the degeneration of cerebellum in spinocerebellar ataxia type 3 (SCA3) patients based on neuroimaging approaches. Forty SCA3 patients were recruited and classified into two subgroups according to their CAG repeat lengths (≥ 74 and < 74). We measured each patient's Scale for the Assessment and Rating of Ataxia (SARA) score, N-acetylaspartate (NAA)/creatine (Cr) ratios based on magnetic resonance spectroscopy (MRS), and 3-dimensional fractal dimension (3D-FD) values derived from magnetic resonance imaging (MRI) results. Furthermore, the 3D-FD values were used to construct structural covariance networks based on graph theoretical analysis. The results revealed that SCA3 patients with a longer CAG repeat length demonstrated earlier disease onset. However, the CAG repeat length did not significantly correlate with their SARA scores, cerebellar NAA/Cr ratios or cerebellar 3D-FD values. Network dissociation between cerebellar regions and parietal-occipital regions was found in SCA3 patients with CAG ≥ 74, but not in those with CAG < 74. In conclusion, the CAG repeat length is uncorrelated with the change of SARA score, cerebellar function and cerebellar structure in SCA3. Nevertheless, a longer CAG repeat length may indicate early structural covariance network dissociation.

Keywords: Brain connectivity; Fractal dimension; Magnetic resonance imaging; Magnetic resonance spectroscopy; NAA; SCA3.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aspartic Acid / analogs & derivatives*
Aspartic Acid / metabolism
Cerebellum* / diagnostic imaging
Cerebellum* / metabolism
Cerebellum* / pathology
Creatine / metabolism*
Cross-Sectional Studies
Female
Humans
Machado-Joseph Disease* / diagnostic imaging
Machado-Joseph Disease* / metabolism
Machado-Joseph Disease* / pathology
Machado-Joseph Disease* / physiopathology
Magnetic Resonance Imaging / methods*
Magnetic Resonance Spectroscopy / methods
Male
Middle Aged
Severity of Illness Index
Trinucleotide Repeats* / genetics

Substances

Aspartic Acid
N-acetylaspartate
Creatine