Evaluation of the glymphatic system in relapsing remitting multiple sclerosis by measuring the diffusion along the perivascular space

Background: In the inflammatory process of multiple sclerosis (MS) several toxic waste products are generated. The clearance of these products might depend on the glymphatic system; however, it's preserved function in MS is uncertain. Recently, it was suggested that this 'waste clearance' system can be examined by measuring the diffusion along the perivascular space (ALPS) index.

Methods: Reproducibility of the ALPS index was tested with intraclass correlation on two open-source datasets with two methods: calculating ALPS indices from the skeleton map (sk-ALPS) and via registration to the common space (ro-ALPS). ALPS indices of 66 MS patient were calculated via the reorientation method. Spearman's correlation and partial least squares regression were applied to reveal the connection between the ALPS indices and the radiological (lesion count) and clinical parameters (SDMT, BVMT, CVLT, EDSS, disease duration) of the patients.

Results: Repeatability of the ALPS index calculated by the ro-ALPS method is the most reliable (ICC: 0.961). Significant correlation was found between the left ALPS index and SDMT. On the right side, significant correlation was found between the ALPS index and the number of periventricular lesions and black holes. The most important predictors of EDSS are disease duration, age, SDMT and infratentorial lesion count.

Conclusion: Reproducibility of the ALPS index ranges from 'good' to 'excellent'. No relationship was found between the ALPS index and clinical disability. A lateralization was observed with cognitive characteristics on the left sided ALPS index and radiological characteristics on the right sided ALPS index.