Glymphatic system activity in functional movement disorder — a link to widespread pain

AIM OF THE STUDY: The study aimed to evaluate glymphatic function in functional movement disorder (FMD) and examine its clinical correlates. CLINICAL RATIONALE FOR THE STUDY: The glymphatic system plays a key role in brain homeostasis by facilitating perivascular clearance of interstitial fluid and metabolic waste, particularly during sleep. The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index provides a non-invasive magnetic resonance imaging-derived (MRI-derived) proxy of glymphatic system activity. The involvement of the glymphatic system in FMD is unknown. MATERIAL AND METHODS: Fifty-four patients with FMD and 52 healthy controls underwent 3T MRI, including DTI. Glymphatic activity was quantified using the DTI-ALPS index. Group differences were assessed with t-tests and analyses of covariance (ANCOVA), controlling for age, gender, and medication status. Associations with clinical measures, including pain intensity - Visual Analog Scale (VAS), Widespread Pain Index (WPI) - fatigue, mood, and motor severity, were examined using Pearson and partial correlations. RESULTS: DTI-ALPS indices did not differ between patients and controls. Compared with healthy controls, patients with FMD showed significantly higher levels of depressive symptoms, fatigue, pain, and somatic symptom burden (all p < 0.001). Among clinical measures, only WPI showed significant negative correlations with ALPS indices (average ALPS index partial r = -0.42; p = 0.004; ALPS index of the right hemisphere partial r = -0.39; p = 0.008; ALPS index of the left hemisphere partial r = -0.38; p = = 0.011), whereas VAS and other clinical symptoms did not. CONCLUSIONS AND CLINICAL IMPLICATIONS: Glymphatic function appears preserved in FMD. In line with previous reports, we found an association with widespread pain experience, suggesting that glymphatic dysfunction could play a role in symptom perception rather than disorder-specific pathology.