Impaired glymphatic clearance in multiple system atrophy: A diffusion spectrum imaging study

Introduction Impaired α-synuclein clearance is pivotal in the pathogenesis of neurodegenerative diseases. We evaluated glymphatic clearance in multiple system atrophy (MSA) patients using advanced imaging. Methods Forty-four MSA patients (11 with MSA-parkinsonian type [MSA-P] and 33 with MSA-cerebellar type [MSA-C]) and 30 healthy controls were studied using diffusion spectrum magnetic resonance imaging (DSI-MRI). Diffusivities were measured along the x-, y-, and z-axes to calculate the Analysis Along the Perivascular Space (ALPS) index. Comparisons of the ALPS index were conducted between MSA patients and controls and among MSA subtypes. The ALPS index correlation with the Unified Multiple System Atrophy Rating Scale (UMSARS) scores was also analyzed. Results The ALPS index differed significantly between patients with MSA and healthy controls, with lower values observed in the former (1.46 ± 0.17 versus1.63 ± 0.12, p < 0.001). Both MSA-P and MSA-C patients had lower ALPS-index (1.40 ± 0.13, p < 0.001; 1.47 ± 0.18, p = 0.003, respectively), but there was no significant difference between the two (p = 0.22). No correlation was found between the ALPS index and clinical scores for UMASRS I (r = −0.08, p = 0.61), UMASRS II (r = −0.04, p = 0.81), or UMASRS I + II (r = −0.05, p = 0.74). Conclusion MSA patients show reduced glymphatic clearance as measured by the ALPS index, underscoring the utility of this imaging method in neurodegenerative disease research.