The impact of enlarged perivascular spaces on the association among peripheral inflammation, disease progression and motor symptoms in Parkinson's disease.

Journal of the neurological sciences 2026

Shi M, Zhao H, Zhu Y, Chen M, Jiang H, Chen Z, Feng M

Abstract

BACKGROUND: The glymphatic system and peripheral inflammation are involved in Parkinson’s disease (PD), but the underlying mechanisms remain unclear. We studied enlarged perivascular spaces (EPVSs) to investigate the interactions among glymphatic system, peripheral inflammation, disease progression and motor symptoms in PD patients. METHODS: This study included 85 PD patients and 87 healthy controls (HCs). Based on MDS-UPDRS score, patients were divided into tremor-dominant (TD) and postural instability and gait difficulty (PIGD) subgroups. The disease stage was assessed using the Hoehn-Yahr (H-Y) scale. We evaluated EPVS number in basal ganglia (BG) and centrum semiovale (CSO), collected serum leukocyte counts and their derived ratios, explored their potential effects on motor symptoms and H-Y stage. RESULTS: The numbers of BG-EPVSs and CSO-EPVSs were significantly greater in PD patients than in HCs. Furthermore, the numbers of BG-EPVSs and CSO-EPVSs were positively correlated with leukocyte, neutrophil, neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), H-Y stage, and motor symptoms and negatively correlated with lymphocyte and lymphocyte-to-monocyte ratio (LMR). However, motor symptoms were positively associated only with neutrophil, NLR, SII, and H-Y stage. Multiple regression analysis confirmed that neutrophil, NLR, SII, and H-Y stage significantly influenced BG-EPVSs numbers, CSO-EPVSs numbers, and MDS-UPDRS III score. Mediation analysis showed that EPVS numbers mediated the relationships among peripheral inflammation, disease progression, and motor symptoms. CONCLUSIONS: The EPVS number is associated with peripheral inflammation and may mediate the effects of peripheral inflammation and disease progression on motor symptoms in PD. EPVSs may serve as an effective indicator of glymphatic system dysfunction.

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