Vasilis Spyridon Tseriotis, Vanessa Carvalho, Elena Moro, Claudio Lino Alberto Bassetti, Mike P Wattjes, Theodoros Mavridis, Anna Alexandratou, Carmen Tur, Edgar Carnero Contentti, Konstantinos Lallas, Aleksandar Sič, Gkirai Chamko, Dimitrios Kavvadas, Theodora Papamitsou, Dimitrios Tsiptsios, Spyridon Konitsiotis, Pavlos Pavlidis, Kyriaki Eleftheriadou, Marianthi Arnaoutoglou
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.