Abstract
OBJECTIVE: The glymphatic system is a major waste clearance system in the central nervous system. We aim to investigate the glymphatic function and its prognostic values in patients with prolonged disorders of consciousness (pDoC). METHODS: We conducted a prospective and explorative cohort study including 40 patients with pDoC and 20 healthy controls. Glymphatic function was measured with the global and regional blood-oxygen-level-dependent and cerebrospinal fluid (BOLD-CSF) couplings, characterized by time-lags and strengths of the couplings. The clinical outcome was defined as improvement and no improvement in consciousness 6 months after enrollment, determined via a structured telephone follow-up based on the Coma Recovery Scale-Revised (CRS-R) score. RESULTS: Patients with pDoC exhibited significantly delayed time-lags in BOLD-CSF coupling (p < 0.05) and significantly reduced coupling strengths (p < 0.05) when compared to healthy controls. Follow-up studies indicated that shorter global BOLD-CSF coupling time-lags can predict an improved consciousness 6 months after enrollment, with an area under the receiver operating characteristic curve of 0.837, a sensitivity of 82.4%, and an accuracy of 85.7% using a cutoff point of 7.5. CONCLUSION: The glymphatic system was impaired in patients with pDoC, and its function, measured by BOLD-CSF coupling, can serve as a novel prognostic biomarker.