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.

中文翻译：

---

多系统萎缩中的广泛白质损伤

多系统萎缩 (MSA) 是一种罕见的神经退行性疾病，其特征是 α-突触核蛋白 (α-syn) 的广泛异常积累。MSA 与帕金森病 (PD) 等其他突触核蛋白病的不同之处在于，α-syn 主要在少突胶质细胞中积累，这是大脑中白质髓鞘形成的唯一来源。以前的 MSA 成像研究发现了白质的局灶性差异。在这里，我们试图通过对全脑白质采取全球视角来巩固这项工作。为此，对 26 名 MSA 患者、26 名健康对照和 23 名 PD 患者进行了体内结构成像和扩散磁共振成像。应用了一种精细的全脑方法，包括主要纤维束和位于皮质地幔边界的浅表白质。p < .001)。此外，在 MSA 患者中，这些异常与运动（统一 MSA 评定量表，第 II 部分）和认知功能（简易精神状态检查）有关。我们观察到的普遍的全脑异常表明 MSA 患者存在广泛的白质损伤，这反映了少突胶质细胞中 α-syn 的广泛聚集。重要的是，全脑白质异常与临床症状相关，这表明白质损伤可能比以前认为的 MSA 更重要。