Dorsolateral nigral hyperintensity in idiopathic REM sleep behavior disorder: a systematic review and meta-analysis

Dorsolateral nigral hyperintensity (DNH) on iron-sensitive MRI is a candidate biomarker of nigrostriatal degeneration. We systematically reviewed evidence on the diagnostic utility of visual DNH assessment in idiopathic REM sleep behavior disorder (iRBD), including concordance with ¹²³I-FP-CIT SPECT and disease stage. MEDLINE, Scopus, Web of Science, ProQuest, and Google Scholar were searched for observational studies assessing DNH in iRBD. Study quality was evaluated using QUADAS-2. Random-effects meta-analyses were performed for diagnostic accuracy and odds ratios (OR), with meta-regression used to explore heterogeneity. Six eligible studies investigated DNH abnormalities in 148 iRBD subjects, 237 PD subjects and 188 healthy controls (HCs), using 3-7T susceptibility-based MRI. Pooled sensitivity and specificity for iRBD-HCs differentiation were 0.54 [0.39; 0.69] (I² = 72.1%) and 0.89 [0.81; 0.94] (I² = 0.0%), respectively, with heterogeneity explained by motor severity in iRBD individuals. DNH abnormalities showed good performance in identifying iRBD individuals with abnormal ¹²³I-FP-CIT SPECT (sensitivity = 0.73 [0.55; 0.86], I² = 30.9%; specificity = 0.77 [0.54; 0.91], I² = 57.2%). PD individuals were significantly more likely to exhibit DNH abnormalities compared to iRBD (pooled OR = 13.06 [1.97-86.55], p = 0.0196); I² = 63.8%). Visual DNH assessment is a specific, non-invasive marker of prodromal alpha-synucleinopathy, but methodological heterogeneity and imprecision warrant standardized imaging and longitudinal validation.