Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK.
Department of Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
J Neurol Neurosurg Psychiatry. 2018 Mar;89(3):248-255. doi: 10.1136/jnnp-2017-316744. Epub 2017 Oct 31.
To assess clinical, electrophysiological and whole-body muscle MRI measurements of progression in patients with motor neuron disease (MND), as tools for future clinical trials, and to probe pathophysiological mechanisms in vivo.
A prospective, longitudinal, observational, clinicoelectrophysiological and radiological cohort study was performed. Twenty-nine patients with MND and 22 age-matched and gender-matched healthy controls were assessed with clinical measures, electrophysiological motor unit number index (MUNIX) and T2-weighted whole-body muscle MRI, at first clinical presentation and 4 months later. Between-group differences and associations were assessed using age-adjusted and gender-adjusted multivariable regression models. Within-subject longitudinal changes were assessed using paired t-tests. Patterns of disease spread were modelled using mixed-effects multivariable regression, assessing associations between muscle relative T2 signal and anatomical adjacency to site of clinical onset.
Patients with MND had 30% higher relative T2 muscle signal than controls at baseline (all regions mean, 95% CI 15% to 45%, p<0.001). Higher T2 signal was associated with greater overall disability (coefficient -0.009, 95% CI -0.017 to -0.001, p=0.023) and with clinical weakness and lower MUNIX in multiple individual muscles. Relative T2 signal in bilateral tibialis anterior increased over 4 months in patients with MND (right: 10.2%, 95% CI 2.0% to 18.4%, p=0.017; left: 14.1%, 95% CI 3.4% to 24.9%, p=0.013). Anatomically, contiguous disease spread on MRI was not apparent in this model.
Whole-body muscle MRI offers a new approach to objective assessment of denervation over short timescales in MND and enables investigation of patterns of disease spread in vivo. Muscles inaccessible to conventional clinical and electrophysiological assessment may be investigated using this methodology.
评估肌萎缩侧索硬化症（MND）患者的临床、电生理和全身肌肉 MRI 测量进展，作为未来临床试验的工具，并探究体内的病理生理机制。
进行了一项前瞻性、纵向、观察性、临床电生理和放射学队列研究。29 例 MND 患者和 22 例年龄和性别匹配的健康对照者在首次临床就诊时和 4 个月后接受临床评估、电生理运动单位数量指数（MUNIX）和 T2 加权全身肌肉 MRI。使用年龄调整和性别调整的多变量回归模型评估组间差异和关联。使用配对 t 检验评估个体内纵向变化。使用混合效应多变量回归模型对疾病传播模式进行建模，评估肌肉相对 T2 信号与临床起始部位解剖毗邻之间的关联。
MND 患者的肌肉相对 T2 信号在基线时比对照组高 30%（所有区域平均值，95%CI 15%至 45%，p<0.001）。较高的 T2 信号与整体残疾程度更高（系数-0.009，95%CI-0.017 至-0.001，p=0.023）以及多个单独肌肉的临床无力和较低的 MUNIX 相关。MND 患者双侧胫骨前肌的相对 T2 信号在 4 个月内增加（右侧：10.2%，95%CI 2.0%至 18.4%，p=0.017；左侧：14.1%，95%CI 3.4%至 24.9%，p=0.013）。在该模型中，MRI 上没有明显的连续疾病传播。
全身肌肉 MRI 为在 MND 中短时间内对失神经进行客观评估提供了一种新方法，并能够在体内研究疾病传播模式。使用这种方法可以研究常规临床和电生理评估不可及的肌肉。
