Multicenter Validation of Metabolic Abnormalities Related to PSP According to the MDS-PSP Criteria

Background and objectives: It remains unclear whether the supportive imaging features described in the diagnostic criteria for progressive supranuclear palsy (PSP) are suitable for the full clinical spectrum. The aim is to define and cross-validate the pattern of glucose metabolism in the brain associated with a diagnosis of different PSP variants. Methods: retrospective, multicenter cohort study performed on 73 PSP patients who were referred for a FDG-PET scan: Richardson's Syndrome (PSP-RS), n=47; parkinsonian variant (PSP-P), n=18; and progressive gait freezing, n=8. Additionally, we included 55 healthy controls (HC) and 58 Parkinson's disease (PD) patients. Scans were normalized by global mean activity. We analyzed the regional differences in metabolism between the groups. Additionally, we applied a multivariate analysis to obtain a PSP related pattern (PSPRP) which was cross-validated in independent populations at individual level. Results: Group analysis showed relative hypometabolism in the midbrain, basal ganglia, thalamus and frontoinsular cortices, and hypermetabolism in the cerebellum and sensorimotor cortices in PSP patients as compared to HC and PD, the latter with more severe involvement in basal ganglia and occipital cortices. The PSPRP obtained confirmed the regions described above. At individual level, the PSPRP showed optimal diagnostic accuracy to distinguish between PSP and HC (sensitivity 80.4% specificity 96.9%), and between PSP and PD (sensitivity 80.4%, specificity 90.7%). Moreover, PSP-RS and PSP-P patients showed significantly more PSPRP expression than PD and HC. Conclusions: the glucose metabolism assessed by FDG-PET is a useful and reproducible supportive diagnostic tool for PSP-RS and PSP-P.