Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN, 55905, USA.
Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN, 55905, USA.
Parkinsonism Relat Disord. 2022 Oct;103:60-68. doi: 10.1016/j.parkreldis.2022.08.028. Epub 2022 Aug 28.
To systematically evaluate structural MRI and diffusion MRI features for cross-sectional discrimination and tracking of longitudinal disease progression in early multiple system atrophy (MSA).
In a prospective, longitudinal study of synucleinopathies with imaging on 14 controls and 29 MSA patients recruited at an early disease stage (15 predominant cerebellar ataxia subtype or MSA-C and 14 predominant parkinsonism subtype or MSA-P), we computed regional morphometric and diffusion MRI features. We identified morphometric features by ranking them based on their ability to distinguish MSA-C from controls and MSA-P from controls and evaluated diffusion changes in these regions. For the top performing regions, we evaluated their utility for tracking longitudinal disease progression using imaging from 12-month follow-up and computed sample size estimates for a hypothetical clinical trial in MSA. We also computed these selected morphometric features in an independent validation dataset.
We found that morphometric changes in the cerebellar white matter, brainstem, and pons can separate early MSA-C patients from controls both cross-sectionally and longitudinally (p < 0.01). The putamen and striatum, though useful for separating early MSA-P patients from control subjects at baseline, were not useful for tracking MSA disease progression. Cerebellum white matter diffusion changes aided in capturing early disease related degeneration in MSA.
Regardless of clinically predominant features at the time of MSA assessment, brainstem and cerebellar pathways progressively deteriorate with disease progression. Quantitative measurements of these regions are promising biomarkers for MSA diagnosis in early disease stage and potential surrogate markers for future MSA clinical trials.
系统评估结构 MRI 和弥散 MRI 特征，以在早期多系统萎缩症（MSA）中进行横断面鉴别和跟踪纵向疾病进展。
在一项前瞻性、纵向研究中，对 14 名对照者和 29 名 MSA 患者进行了影像学检查，这些患者在疾病早期阶段（15 名主要小脑共济失调亚型或 MSA-C 和 14 名主要帕金森病亚型或 MSA-P）被招募。我们计算了区域形态和弥散 MRI 特征。我们通过基于它们区分 MSA-C 与对照组以及 MSA-P 与对照组的能力对形态特征进行排名，并评估了这些区域的弥散变化。对于表现最佳的区域，我们使用 12 个月随访的影像学评估它们用于跟踪纵向疾病进展的效用，并计算了 MSA 假设临床试验的样本量估计。我们还在独立的验证数据集中计算了这些选定的形态特征。
我们发现，小脑白质、脑干和脑桥的形态变化可以在横断面和纵向区分早期 MSA-C 患者与对照组（p < 0.01）。虽然在基线时，壳核和纹状体有助于区分早期 MSA-P 患者与对照者，但它们对于跟踪 MSA 疾病进展没有帮助。小脑白质弥散变化有助于捕捉 MSA 早期疾病相关的退行性变。
无论在 MSA 评估时是否具有临床主要特征，脑干和小脑通路都会随着疾病的进展而逐渐恶化。这些区域的定量测量是 MSA 早期疾病阶段诊断的有前途的生物标志物，也是未来 MSA 临床试验的潜在替代标志物。
