Impaired glymphatic system for upper limb motor dysfunction in patients with acute ischemic stroke

Acute ischemic stroke (AIS) is a common cerebrovascular disease associated with insufficient brain perfusion and accumulation of waste materials, which may further impair the glymphatic system. We aimed to investigate glymphatic activity using the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) method and assess its correlation with upper limb motor dysfunction in AIS patients, as well as identify factors associated with these changes.

We prospectively enrolled 59 patients with AIS [mean age: 62.4; males: 40; mean symptoms onset to magnetic resonance imaging (MRI): 5.9 days] and 29 age- and sex-matched healthy controls (HCs), among whom 18 patients underwent a second MRI scan. The ALPS index was utilized to assess glymphatic function. We compared the ALPS index between AIS patients and the HCs group in both hemispheres. Additionally, we investigated the association between ALPS index on the side of infarction and clinical variables including time since stroke onset, infarct volume, Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) scores, and National Institutes of Health Stroke Scale (NIHSS) scores. Furthermore, we examined changes in ALPS index from baseline to follow-up in 2 months.

Among 59 patients, 27 (45.8%) had left hemispheric infarct. The mean ALPS index on the ipsilateral side of the AIS patients was significantly lower than that on the contralateral side (1.225±0.132 vs. 1.337±0.138, P<0.001) and the corresponding side in the HCs group (P<0.001). Additionally, the mean ALPS index on the contralateral side of the infarct was significantly lower when compared to the corresponding side in the HC group (1.233±0.078 vs. 1.450±0.211 on the left side; 1.217±0.165 vs. 1.450±0.155 on the right side, both P<0.001). The ALPS index demonstrates a significant positive correlation (ρ=0.404, P=0.001) with FMA-UE and a notable negative correlation (ρ=-0.484, P<0.001) with the NIHSS score. However, subsequent MRI follow-up of the 18 patients revealed a statistically significant elevation in the ALPS index compared to baseline (1.296±0.141 vs. 1.174±0.109, P=0.001).

Our findings suggest that a decreased ALPS index in AIS patients with upper limb motor dysfunction indicates impaired glymphatic function. Moreover, the level of the ALPS index is associated with the severity of stroke. ALPS index could be a potential neuroimaging biomarker for AIS patients with upper limb motor dysfunction.