MRI-based brain structural changes in adult-onset dentatorubral-pallidoluysian atrophy.

BACKGROUND AND PURPOSE: Adult-onset dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant spinocerebellar ataxia subtype, characterized by widespread brain neurodegeneration. However, comprehensive studies on whole-brain structural changes remain limited. This study aimed to quantify brain structural damage in adult-onset DRPLA and correlate these findings with clinical data.

METHODS

Twenty-four adult-onset DRPLA patients were recruited and underwent structural and diffusion MRI at 3.0 Tesla. Multimodal analyses were conducted to assess cortical thickness, the volumes of subcortical structures, the brainstem, cerebellum, and cerebral white matter (WM), as well as the microstructural integrity of WM. Results were compared with those from 30 age- and gender-matched healthy controls. The relationships between neuroimaging abnormalities and clinical data, including ataxia severity, cognitive performance, CAG repeat length, and disease duration, were explored.

RESULTS

In adult-onset DRPLA patients, reduced cortical thickness was observed in the bilateral frontal, parietal, temporal, and occipital lobes. Volumetric analysis revealed significant reductions in all subcortical structures, as well as in the brainstem, cerebellum, and cerebral WM substructures. Tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics demonstrated widespread WM abnormalities throughout the brain. Furthermore, several imaging measures demonstrated significant correlations with ataxia severity, cognitive function scores, CAG repeat length, and disease duration.

CONCLUSION

DRPLA should be considered a multisystem neurodegenerative disease, characterized by widespread and severe gray matter and WM atrophy throughout the brain. The advanced MRI techniques employed in this study expand our understanding of the underlying pathophysiological mechanisms.