# Glymphatic Function as a Prognostic Biomarker in Prolonged Disorders of Consciousness

## TL;DR

This study shows that impaired glymphatic function, measured via MRI, can predict recovery of consciousness in patients with prolonged disorders of consciousness.

## Contribution

Glymphatic function, measured by BOLD-CSF coupling, is proposed as a novel prognostic biomarker for consciousness recovery in pDoC.

## Key findings

- pDoC patients showed significantly delayed BOLD-CSF coupling time-lags compared to healthy controls.
- Shorter global BOLD-CSF coupling time-lags predicted improved consciousness with high accuracy.
- Glymphatic dysfunction is associated with impaired consciousness recovery in pDoC patients.

## Abstract

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).

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.

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.

The glymphatic system was impaired in patients with pDoC, and its function, measured by BOLD‐CSF coupling, can serve as a novel prognostic biomarker.

This study examines glymphatic dysfunction in pDoC via BOLD‐CSF coupling analysis using MRI. pDoC patients show delayed time‐lags and reduced coupling strengths, with time‐lags predicting consciousness recovery. Findings suggest glymphatic dysfunction as a potential biomarker for consciousness recovery in pDoC.