Nigral glucose metabolism as a diagnostic marker of neurodegenerative parkinsonian syndromes

Parkinson’s disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) are characterized by nigrostriatal degeneration. We used [(18)F]FDG PET to assess glucose metabolism of the substantia nigra (SN) in patients with these diseases and evaluated its ability to discriminate neurodegenerative parkinsonian syndromes (NP) from controls. We retrospectively evaluated [(18)F]FDG PET scans of 171 patients with NP (n = 115 PD, n = 35 MSA, n = 21 PSP) and 48 controls (13 healthy controls [HC] and 35 control patients). Mean normalized bilateral [(18)F]FDG uptake in the SN was calculated and compared between groups with covariance and receiver operating characteristic (ROC) analyses (selection of the optimal cut-off required a minimum specificity of 90% to meet the clinical need of a confirmatory test). PD patients were additionally stratified by the expression of the well-established PD-related metabolic pattern (PDRP; elevated expression defined as 2 standard deviations above the mean value of HC). [(18)F]FDG uptake was significantly lower in NP (Cohen’s d = 1.09, p < 0.001) and its subgroups (PD, d = 1.10, p < 0.001; MSA, d = 0.97, p < 0.001; PSP, d = 1.79, p < 0.001) than in controls. ROC analysis for discriminating NP vs. controls revealed an area under the curve of 0.81 and a sensitivity and specificity of 56 and 92%. Moreover, nigral metabolism was below the cut-off in 60% of PD patients without elevated PDRP expression. Glucose metabolism of the SN can distinguish patients with NP from controls with good diagnostic accuracy and can be used as a marker of nigral degeneration. Its evaluation is particularly valuable in PD patients without elevated PDRP expression and may thus help to narrow the diagnostic gap of [(18)F]FDG PET in neurodegenerative parkinsonism (i.e., identification of patients with PD without cortical involvement).