Magnetic Resonance Imaging and Its Clinical Correlation in Spinocerebellar Ataxia Type 3: A Systematic Review

Spinocerebellar ataxia type 3 (SCA3) is a complex cerebrocerebellar disease primarily characterized by ataxia symptoms alongside motor and cognitive impairments. The heterogeneous clinical presentation of SCA3 necessitates correlations between magnetic resonance imaging (MRI) and clinical findings in reflecting progressive disease changes. At present, an attempt to systematically examine the brain-behavior relationship in SCA3, specifically, the correlation between MRI and clinical findings, is lacking.We investigated the association strength between MRI abnormality and each clinical symptom to understand the brain-behavior relationship in SCA3.We conducted a systematic review on Medline and Scopus to review studies evaluating the brain MRI profile of SCA3 using structural MRI (volumetric, voxel-based morphometry, surface analysis), magnetic resonance spectroscopy, and diffusion tensor imaging, including their correlations with clinical outcomes.Of 1,767 articles identified, 29 articles met the eligibility criteria. According to the National Institutes of Health quality assessment tool for case-control studies, all articles were of excellent quality. This systematic review found that SCA3 neuropathology contributes to widespread brain degeneration, affecting the cerebellum and brainstem. The disease gradually impedes the cerebral cortex and basal ganglia in the late stages of SCA3. Most findings reported moderate correlations (r = 0.30-0.49) between MRI features in several regions and clinical findings. Regardless of the MRI techniques, most studies focused on the brainstem and cerebellum.Clinical findings suggest that rather than individual brain regions, the connectivity between different brain regions in distributed networks (i.e., cerebellar-cerebral network) may be responsible for motor and neurocognitive function in SCA3. This review highlights the importance of evaluating the progressive changes of the cerebellar-cerebral networks in SCA3 patients, specifically the functional connectivity. Given the relative lack of knowledge about functional connectivity on SCA3, future studies should investigate possible functional connectivity abnormalities in SCA3 using fMRI.