Differential Neural Substrates of Freezing of Gait in Cerebral Small Vessel Disease and Parkinson Disease: A Dual-tracer PET Study.

Abstract

Freezing of gait (FOG) occurs in both Parkinson disease (PD) and cerebral small vessel disease (CSVD), but its mechanism in CSVD is unknown. We hypothesize that FOG arises from distinct neural substrates in these 2 disorders. This cross-sectional study included 7 CSVD patients with FOG, 7 PD patients with FOG, and 20 healthy controls. All underwent clinical assessment and dual-tracer PET ( 18 F-FDG for metabolism; 11 C-CFT for dopamine transporter (DAT) binding). Group comparisons and clinical correlations were performed. CSVD-FOG patients showed relatively lower 18 F-FDG uptake in frontal-striatal and posterior cingulate regions, accompanied by relatively higher uptake in temporal-occipital-cerebellar areas after whole-brain normalization. By contrast, PD-FOG patients exhibited relatively higher striatal 18 F-FDG uptake and relatively lower uptake in parietal-temporal regions. Critically, DAT binding was severely reduced in PD, while relatively preserved DAT binding was observed in CSVD patients compared with PD. In the CSVD group, higher putaminal 18 F-FDG SUVr was associated with faster gait speed and lower FOG severity. FOG in PD and CSVD is associated with divergent dopaminergic and metabolic imaging patterns. PD-FOG is characterized by marked nigrostriatal DAT reduction, whereas CSVD-FOG shows relatively preserved DAT binding compared with PD and distinct whole-brain-normalized 18 F-FDG uptake patterns, suggesting involvement of neural networks beyond primary nigrostriatal dopaminergic pathways. These imaging differences may support etiology-informed diagnostic considerations and individualized management strategies.