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

Abstract

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 of the current study was to define and cross-validate the pattern of glucose metabolism in the brain associated with a diagnosis of different PSP variants. A retrospective multicenter cohort study performed on 73 PSP patients who were referred for a fluorodeoxyglucose positron emission tomography PET scan: PSP-Richardson's syndrome, n = 47; PSP-parkinsonian variant, n = 18; and progressive gait freezing, n = 8. In addition, we included 55 healthy controls and 58 Parkinson's disease (PD) patients. Scans were normalized by global mean activity. We analyzed the regional differences in metabolism between the groups. Moreover, we applied a multivariate analysis to obtain a PSP-related pattern that was cross-validated in independent populations at the individual level. 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 compared with healthy controls and PD patients, the latter with more severe involvement in the basal ganglia and occipital cortices. The PSP-related pattern obtained confirmed the regions described above. At the individual level, the PSPrelated pattern showed optimal diagnostic accuracy to distinguish between PSP and healthy controls (sensitivity, 80.4%; specificity, 96.9%) and between PSP and PD (sensitivity, 80.4%; specificity, 90.7%). Moreover, PSP-Richardson's syndrome and PSP-parkinsonian variant patients showed significantly more PSP-related pattern expression than PD patients and healthy controls. The glucose metabolism assessed by fluorodeoxyglucose PET is a useful and reproducible supportive diagnostic tool for PSP-Richardson's syndrome and PSP-parkinsonian variant.

EANM procedure guidelines for brain PET imaging using [18F]FDG, version 3

“…These patterns have been described based on qualitative interpretation and semiquantitative analysis using voxel-based analysis or principal component analyses with the estimation of spatial covariance patterns (i.e. metabolic connectivity) [33][34][35][36][37][38][39][40]. Cortical hypometabolism in temporooccipital and parietal regions has also been described in PD-MCI or PD patients that develop dementia at follow-up [33].…”

Stereotyped Relationship Between Motor and Cognitive Metabolic Networks in Parkinson's Disease

“…Even so, the simpler model based on PDRP and delta has a number of advantages. Unlike PDRP and PDCP, MSARP and PSPRP have not been extensively validated across centers and imaging platforms 33,34,48‐50 . This is particularly relevant in the rs‐fMRI domain in which PDRP and PDCP networks have recently been identified and validated, 6,39,44 whereas MSA‐ and PSP‐related networks analogous to those identified using FDG‐PET have yet to be characterized using this modality.…”

“…Unlike PDRP and PDCP, MSARP and PSPRP have not been extensively validated across centers and imaging platforms. 33,34,[48][49][50] This is particularly relevant in the rs-fMRI domain in which PDRP and PDCP networks have recently been identified and validated, 6,39,44 whereas MSA-and PSP-related networks analogous to those identified using FDG-PET have yet to be characterized using this modality. Our preliminary results suggest that the stereotyped relationship between PDRP and PDCP can also be discerned using noninvasive rs-fMRI techniques, which are better suited for large-scale clinical trials and potential diagnostic use.…”

Progressive supranuclear palsy and corticobasal degeneration: novel clinical concepts and advances in biomarkers

“…Concerning PSP, however, there is still uncertainty regarding its usefulness in distinguishing PSP clinical variants. A previous study demonstrated that FDG-PET is a reproducible diagnostic tool for PSP-RS and PSP-P variants 68 .…”