The Significance and Mechanism of Cerebral Enlarged Perivascular Space in Amyotrophic Lateral Sclerosis
Journal
International Journal of Molecular Sciences
Journal Volume
26
Journal Issue
19
Start Page
9474
ISSN
1661-6596
Date Issued
2025-10
Author(s)
Kuo, Yih-Chih
Cheng, Lo-Fan
Tsai, Yi-Chieh
Huang, Jia-Zheng
Lin, Jhih-Syuan
Huang, Po-Ya
Ting, Chen-Hung
Lai, Hsing-Jung
Abstract
Enlarged perivascular spaces (EPVS) are MRI markers of impaired glymphatic clearance and have been associated with neurodegenerative diseases. However, their clinical significance in amyotrophic lateral sclerosis (ALS) and underlying mechanisms remain poorly understood. This study investigated the prevalence, clinical relevance, and pathophysiological basis of EPVS in ALS. MRI data from 114 ALS patients and 119 matched controls were analyzed, with high-degree EPVS defined as more than 20 visible spaces. High-degree EPVS in the centrum semiovale (CSO) was more prevalent in ALS patients (49.1%) than in controls (15.1%, < 0.001). Age, male sex, and ALS diagnosis were independent predictors, while disease severity and aggressiveness were not associated. ALS patients with high-degree CSO-EPVS were older at disease onset and MRI but showed similar clinical progression. In SOD1/G93A ALS mice, cerebral perivascular spaces were significantly enlarged at 5 months compared to wild-type and younger ALS mice. Cervical lymphatic ligation promoted misfolded SOD1 accumulation in motor neurons and cerebral vessels, further increasing perivascular space width without altering motor function. These findings suggest that about half of ALS patients exhibit high-degree CSO-EPVS, reflecting impaired protein clearance rather than disease aggressiveness.
Subjects
amyotrophic lateral sclerosis (ALS)
animal model
enlarged perivascular space
magnetic resonance imaging (MRI)
misfolded protein
superoxide dismutase type 1
Type
journal article