Glymphatic Reserve as a Determinant of Responsiveness to Neurological Rehabilitation: A Hypothesis

Recovery after acquired neurological injury is highly heterogeneous. Some patients improve rapidly with standard rehabilitation, whereas others recover slowly despite comparable lesion characteristics, comorbidity profiles, and therapy. The glymphatic system supports clearance of metabolic waste, neurotoxic proteins, excess interstitial fluid, and inflammatory mediators from the brain. This hypothesis proposes that a clinically meaningful subgroup of neurological rehabilitation patients has reduced glymphatic function, which contributes to slower functional gains through prolonged neuroinflammation, impaired proteostasis, edema persistence, sleep fragmentation, and reduced plasticity efficiency. Therefore, a glymphatic-optimized rehabilitation approach may improve recovery trajectories in individuals with low glymphatic reserve. As a result, impaired glymphatic function may represent an under-recognized biological determinant of rehabilitation responsiveness and prognosis.