[18F]fluordeoxyglucose positron emission tomography in spinocerebellar ataxias type 1,2,3 and 6

Introduction: The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of autosomal dominant ataxias. Some mutations, including SCA 1,2, and 3 are multisystemic disorders, characterized by a variety of noncerebellar symptoms, while others, like SCA 6, give rise to a pure cerebellar syndrome. Functional imaging studies so far have reported decreased glucose metabolism in the cerebellum and brainstem. The present study therefore aimed to identify specific local cerebral metabolic patterns associated with a given SCA mutation using [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET).

Methods: Up to now 12 healthy controls (47,5±12,5 years, m/f: 6/6), 7 SCA 1 patients (43±12 years, m/f: 3/4), 5 SCA 2 patients (45,6±11,4 years, m/f: 3/2), 15 SCA 3 patients (42,7±9,7 years, m/f: 9/6) and 8 SCA 6 patients (60,3±8,9 years, m/f: 6/2) were examined. Each participant was examined clinically using the Scale for assessment and rating of ataxia (SARA), neuropsychological testing and a 60min dynamic FDG-PET with arterial bloodsampling and a 3D-T1-weighted MRI. After movement correction and coregistration with MRI metabolic images of the local cerebral metabolic rate of glucose consumption (LCMRglu) were calculated using the Patlak plot calculation and spatially normalized in respect to the MNI-PET-template defined in SPM2. In a preliminary statistical analysis with SPM2 we performed a 2 sample-t-test using proportional scaling and an uncorrected threshold of 0.005.

Results: We found a reduction of LCMRglu in SCA1 patients in brainstem, cerebellum (more pronounced in the vermis) and thalamus, in SCA 2 patients in the cerebellum (hemispheres and vermis), lower pons and occipital pole, in SCA 3 patients in brainstem, cerebellum and thalamus, and in SCA 6 patients in cerebellum and several cortical areas (frontotemporal, occipital). Increased LCMRglu was found in SCA 1 in frontal, parietal and occipital regions, in SCA 2 and SCA 3 in subcortical areas throughout the brain and in SCA 6 in subcortical regions of the frontal and occipital lobes.

Conclusion: All SCAs showed widespread infra- and supratentorial changes of glucose metabolism. Interestingly SCA 6 which has been regarded a pure cerebellar syndrome, resulted in pronounced changes in frontal and occipital lobes. In the absence of histopathological changes these changes may compensate for disconnection of cerebello-cortical tracts.