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 (K(trans)) in dynamic contrast-enhanced MRI (DCE-MRI). CSF-AI and K(trans) 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 K(trans) and unified MSA rating scale (UMSARS). K(trans) 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 K(trans) (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.