Clinical and Preclinical Neuroimaging Changes in Spinocerebellar Ataxia Type 12: A Study of Three Chinese Pedigrees

Abstract

<b><i>Background:</i></b> Spinocerebellar ataxia type 12 (SCA12) is a rare SCA subtype with unclear clinical and imaging features. Also, the radiological changes in prodromal and early stages remain unknown. <b><i>Methods:</i></b> Ten symptomatic and two pre­symptomatic cases from three Chinese pedigrees received clinical assessments and imaging studies including routine magnetic resonance imaging (MRI), diffusion kurtosis imaging (DKI), and positron emission tomography (PET) using ¹⁸F-flurodeoxyglucose (FDG) to investigate glucose metabolism in brain and ¹⁸F-vesicle monoamine transporter 2 (VMAT2) to inspect the integrity of the dopaminergic neuron. Seventy-two healthy individuals were recruited as controls in the quantitative FDG-PET analysis. Imaging parameters were compared between symptomatic and presymptomatic cases with different disease durations. <b><i>Results:</i></b> Patients displayed prominent action tremor, moderate ataxia, and subtle parkinsonism with poor levodopa-response. MRI showed extensive but heterogeneous cerebral atrophy, which was most evident in the frontoparietal lobes. Cerebellar atrophy was apparent in later stages. DKI detected impaired fibers in the cerebellar peduncles. In both symptomatic and pre­symptomatic cases, PET-CT showed an earlier FDG decline than atrophic changes in multiple regions, and the frontoparietal lobes were the earliest and most severe. However, the VMAT2 density were normal in the putamen and caudate nucleus of most cases (7/8). <b><i>Conclusions:</i></b> We first found that hypometabolism in the cerebral cortex, but not cerebellum, is an early and prominent change in SCA12. The integrity of presynaptic dopaminergic neurons remains largely spared during the whole disease process.