Blood–brain barrier impairment is functionally correlated with clinical severity in patients of multiple system atrophy

Multiple system atrophy (MSA) has been regarded as a unique entity within the spectrum of oligodendrogliopathy. However, the pathomechanisms underlying the initial trigger and aggravating factors responsible for disease progression remain unknown. Even though the implication of blood–brain barrier (BBB) dysfunction has not been fully elucidated, this dysfunction may act as a modifier of disease progression in neurodegenerative disease.We evaluated the integrity of the BBB and its functional significance in patients with MSA using the CSF/serum albumin index (CSF-AI) and the volume transfer coefficient (Ktrans) in dynamic contrast-enhanced MRI (DCE-MRI). CSF-AI and Ktrans values increased significantly in patients with MSA compared to the control (5.1 μg vs 3.6 μg, p = 0.02; 0.16/mim−1 vs 0.05/mim−1, p = 0.001, respectively). There were positive relationships between both CSF-AI and Ktrans and unified MSA rating scale (UMSARS). Ktrans in the periventricular white matter was significantly correlated with the volume of white matter hyperintensities among all subjects (r = 0.58, p = 0.001) and within patients with MSA (r = 0.58, p = 0.019), but not within controls (r = 0.42, p > 0.05). In addition, a significant positive correlation was detected between CSF-AI and Ktrans (r = 0.81, p = 0.002). Multiple linear regression analysis showed that only UMSARS score was a significantly independent predisposing factor for CSF-AI (β = 0.193, p = 0.04). Our data suggest that BBB dysfunction is related to the underlying nature of MSA and its dysfunction is closely coupled to disease severity.