Broad white matter impairment in multiple system atrophy

• Main Authors: Brefel-Courbon, C. (Author), Del Campo, N. (Author), Galitzky, M. (Author), Joshi, S. (Author), Narr, K.L (Author), Ory-Magne, F. (Author), Pavy-LeTraon, A. (Author), Péran, P. (Author), Phillips, O. (Author), Rascol, O. (Author), Singh, M.K (Author), Thalamas, C. (Author)
• Format: Article
• Language: English
• Published: John Wiley and Sons Inc 2021
• Subjects: adult; aged; Aged; alpha synuclein; Article; axial diffusivity; clinical article; cognition; controlled study; diagnostic imaging; diffusion tensor imaging; diffusion weighted imaging; echo planar imaging; female; Female; fractional anisotropy; human; Humans; image processing; in vivo study; Magnetic Resonance Imaging; male; Male; mean diffusivity; middle aged; Middle Aged; Mini Mental State Examination; MRI; multiple system atrophy; Multiple System Atrophy; neuroimaging; nuclear magnetic resonance imaging; oligodendroglia; Parkinson disease; pathophysiology; priority journal; procedures; radial diffusivity; Shy Drager syndrome; three-dimensional imaging; Unified Parkinson Disease Rating Scale; white matter; White Matter; white matter lesion
• Online Access: View Fulltext in Publisher

 Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by the widespread aberrant accumulation of α-synuclein (α-syn). MSA differs from other synucleinopathies such as Parkinson's disease (PD) in that α-syn accumulates primarily in oligodendrocytes, the only source of white matter myelination in the brain. Previous MSA imaging studies have uncovered focal differences in white matter. Here, we sought to build on this work by taking a global perspective on whole brain white matter. In order to do this, in vivo structural imaging and diffusion magnetic resonance imaging were acquired on 26 MSA patients, 26 healthy controls, and 23 PD patients. A refined whole brain approach encompassing the major fiber tracts and the superficial white matter located at the boundary of the cortical mantle was applied. The primary observation was that MSA but not PD patients had whole brain deep and superficial white matter diffusivity abnormalities (p <.001). In addition, in MSA patients, these abnormalities were associated with motor (Unified MSA Rating Scale, Part II) and cognitive functions (Mini-Mental State Examination). The pervasive whole brain abnormalities we observe suggest that there is widespread white matter damage in MSA patients which mirrors the widespread aggregation of α-syn in oligodendrocytes. Importantly, whole brain white matter abnormalities were associated with clinical symptoms, suggesting that white matter impairment may be more central to MSA than previously thought. © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.