[11C](R)-PK11195 Positron Emission Tomography Imaging of Skull Inflammation in Isolated Rapid-Eye-Movement Sleep Behavior Disorder.

BACKGROUND: Skull bone marrow is a specialized immune compartment supplying cells to the meninges. Experimental evidence suggests skull marrow activity may contribute to neuroinflammation in early Parkinson's disease, but in vivo assessment has not yet been performed in any α-synucleinopathy. OBJECTIVE: The objective is to assess skull/meningeal inflammatory activity in patients with isolated rapid-eye-movement sleep behavior disorder (iRBD). METHODS: 20 iRBD patients recieved longitudinal [11C](R)-PK11195 positron emission tomography scans and were compared to 19 healthy controls. RESULTS: Global skull inflammation in the iRBD patients was 22.87% higher (95% confidence interval: 12.78-32.97) compared to controls, especially in frontal regions, differing from that previously reported in Alzheimer's disease and multiple sclerosis. This inflammation progressed during a 3-year follow-up period but did not correlate with phenoconversion. CONCLUSION: This is the first in vivo evidence of skull marrow activation in an α-synucleinopathy. Our findings support a role for the skull-meningeal immune axis in iRBD, linking peripheral and central inflammation in prodromal disease. © 2025 International Parkinson and Movement Disorder Society.