Lateralized glymphatic system impairment in acute ischemic stroke: a DTI-ALPS study of upper limb motor function

The glymphatic system (GS) is a brain-specific waste clearance pathway essential for maintaining cerebral homeostasis. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) provides a non-invasive means of evaluating GS function. However, the characteristics of GS impairment in acute ischemic stroke (AIS) and their relationship with clinical function remain incompletely understood.

Sixty-nine patients with AIS (35 left-sided infarction, 34 right-sided infarction) and 34 healthy controls (HCs) were enrolled. All patients underwent 3.0 T MRI within 72 h of onset. Bilateral DTI-ALPS indices were calculated using an automated ROI algorithm. Neurological and motor functions were assessed with the National Institutes of Health Stroke Scale (NIHSS) and the Fugl-Meyer Assessment-Upper Extremity (FMA-UE). Partial correlation analyses, controlling for age, sex and years of education, examined associations between DTI-ALPS indices and clinical scale scores.

Among right-handed HCs, the left-hemisphere DTI-ALPS index was significantly higher than the right (P < 0.0001), indicating physiological lateralization of GS clearance capacity. Compared with HCs, both the left- and right-sided infarction groups exhibited significantly reduced left hemisphere DTI-ALPS indices (P < 0.05), whereas right hemisphere indices did not differ significantly regardless of infarct side. In the left infarction group, the left hemisphere DTI-ALPS index was negatively correlated with NIHSS scores (r = -0.418, P = 0.017) and positively correlated with FMA-UE scores (r = 0.392, P = 0.026). In the right infarction group, the left hemisphere DTI-ALPS index showed a positive correlation with FMA-UE scores (r = 0.513, P = 0.003).

These findings suggest physiological lateralization of GS function with left hemispheric predominance in right-handed individuals. AIS produces a left-dominant pattern of GS impairment that is independent of infarct laterality. The left hemisphere DTI-ALPS index may represent a promising, lateralization-independent biomarker for upper limb motor function assessment in the acute phase of stroke.