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.
Department of Neurology and Brain Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
Sook K
SK
Song
Seung-Koo
SK
Lee
Jae Jung
JJ
Lee
Ji E
JE
Lee
Hyun Seok
HS
Choi
Young H
YH
Sohn
Phil Hyu
PH
Lee
D000368:Aged; D001812:Blood-Brain Barrier / Q000473:pathology* / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000134:cerebrospinal fluid* / Q000473:pathology*; D011446:Prospective Studies; D012720:Severity of Illness Index