Glymphatic Dysfunction in Patients With Ischemic Stroke.

Cheng Hong Toh,Tiing Yee Siow

doi:10.3389/fnagi.2021.756249

Cheng Hong Toh, Tiing Yee Siow

Open Access

https://doi.org/10.3389/fnagi.2021.756249

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Abstract

Objectives: Rodent experiments have provided some insight into the changes of glymphatic function in ischemic stroke. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) method offers an opportunity for the noninvasive investigation of the glymphatic system in patients with ischemic stroke. We aimed to investigate the changes of glymphatic function in ischemic stroke and the factors associated with the changes.Materials and Methods: A total of 50 patients (mean age 56.7 years; 30 men) and 44 normal subjects (mean age 53.3 years; 23 men) who had preoperative diffusion-tensor imaging for calculation of the analysis along the perivascular space (ALPS) index were retrospectively included. Information collected from each patient included sex, age, time since stroke onset, infarct location, hemorrhagic change, infarct volume, infarct apparent diffusion coefficient (ADC), infarct fractional anisotropy (FA), and ALPS index of both hemispheres. Interhemispheric differences in ALPS index (infarct side vs. contralateral normal side) were assessed with a paired t-test in all patients. ALPS index was normalized by calculating ALPS ratios (right-to-left and left-to-right) for comparisons between patients and normal subjects. Comparisons of ALPS ratios between patients and normal subjects were performed using analysis of covariance with adjustments for age and sex. Linear regression analyses were performed to identify factors associated with the ALPS index.Results: In patients, the mean ALPS index ipsilateral to infarct was 1.162 ± 0.126, significantly lower (P < 0.001) than that of the contralateral side (1.335 ± 0.160). The right-to-left ALPS index ratio of patients with right cerebral infarct was 0.84 ± 0.08, significantly lower (P < 0.001) than that of normal subjects (0.95 ± 0.07). The left-to-right ALPS ratio of patients with left cerebral infarct was 0.92 ± 0.09, significantly (P < 0.001) lower than that of normal subjects (1.05 ± 0.08). On multiple linear regression analysis, time since stroke onset (β = 0.794, P < 0.001) was the only factor associated with the ALPS index.Conclusion: The ALPS index showed lower values in ischemic stroke suggesting impaired glymphatic function. Following initial impairment, the ALPS index increased with the time since stroke onset, which is suggestive of glymphatic function recovery.

Highlights

The glymphatic system has been recently recognized as a pathway for waste clearance and maintaining fluid balance in the brain’s parenchymal interstitium (Rasmussen et al, 2018)
We aimed to investigate the changes of the along the perivascular space (ALPS) index, which suggests a glymphatic function in ischemic stroke, and factors associated with the changes
There were excellent interobserver agreements in the measurements of infarct volumes (ICC = 0.802, 95% confidence intervals (CIs) = 0.792–0.814, P < 0.001), infarct apparent diffusion coefficient (ADC) (ICC = 0.956, 95% CI = 0.950–0.958, P < 0.001), infarct Fractional anisotropy (FA) (ICC = 0.912, 95% CI = 0.906–0.918, P < 0.001), and bilateral ALPS indices (ICC = 0.838, 95% CI = 0.821–0.844, P < 0.001)

Summary

Introduction

The glymphatic system has been recently recognized as a pathway for waste clearance and maintaining fluid balance in the brain’s parenchymal interstitium (Rasmussen et al, 2018). The discovery of the glymphatic system led to a new perspective on the pathogenesis of many brain diseases including ischemic stroke (Mestre et al, 2020). Rodent experiments have provided some insights into the changes in glymphatic function associated with ischemic stroke. It is widely accepted that interstitial fluid clearance in the glymphatic system is reduced after ischemic infarct (Ji et al, 2021; Lv et al, 2021). Understanding the role of the glymphatic system in the pathophysiological process of ischemic stroke may help develop treatments that promote poststroke functional recovery. Comprehensive human research on the glymphatic system, is limited by the invasiveness of current evaluation tools (e.g., intrathecal contrast medium injection) (Ringstad et al, 2018; Edeklev et al, 2019; Watts et al, 2019)

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