Tahedl Marlene, Tan Ee Ling, Shing Stacey Li Hi, Chipika Rangariroyashe H, Siah We Fong, Hengeveld Jennifer C, Doherty Mark A, McLaughlin Russell L, Hardiman Orla, Finegan Eoin, Bede Peter
Computational Neuroimaging Group (CNG), Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.
Eur J Neurol. 2023 May;30(5):1232-1245. doi: 10.1111/ene.15725. Epub 2023 Mar 1.
Primary lateral sclerosis (PLS) is a progressive upper motor neuron disorder associated with considerable clinical disability. Symptoms are typically exclusively linked to primary motor cortex degeneration and the contribution of pre-motor, supplementary motor, cortico-medullary and inter-hemispheric connectivity alterations are less well characterized.
In a single-centre, prospective, longitudinal neuroimaging study 41 patients with PLS were investigated. Patients underwent standardized neuroimaging, genetic profiling with whole exome sequencing, and comprehensive clinical assessments including upper motor neuron scores, tapping rates, mirror movements, spasticity assessment, cognitive screening and evaluation for pseudobulbar affect. Longitudinal neuroimaging data from 108 healthy controls were used for image interpretation. A standardized imaging protocol was implemented including 3D T1-weighted structural, diffusion tensor imaging and resting-state functional magnetic resonance imaging. Following somatotopic segmentation, cortical thickness analyses, probabilistic tractography, blood oxygenation level dependent signal analyses and brainstem volumetry were conducted to evaluate cortical, brainstem, cortico-medullary and inter-hemispheric connectivity alterations both cross-sectionally and longitudinally.
Our data confirm progressive primary motor cortex degeneration, considerable supplementary motor and pre-motor area involvement, progressive brainstem atrophy, cortico-medullary and inter-hemispheric disconnection, and close associations between clinical upper motor neuron scores and somatotopic connectivity indices in PLS.
Primary lateral sclerosis is associated with relentlessly progressive motor connectome degeneration. Clinical disability in PLS is likely to stem from a combination of intra- and inter-hemispheric connectivity decline and primary, pre- and supplementary motor cortex degeneration. Simple 'bedside' clinical tools, such as tapping rates, are excellent proxies of the integrity of the relevant fibres of the contralateral corticospinal tract.
原发性侧索硬化症（PLS）是一种进行性上运动神经元疾病，会导致严重的临床残疾。症状通常仅与初级运动皮层变性有关，而运动前区、辅助运动区、皮质延髓和半球间连接改变的作用则不太明确。
在一项单中心、前瞻性、纵向神经影像学研究中，对41例PLS患者进行了调查。患者接受了标准化神经影像学检查、全外显子测序的基因分析，以及包括上运动神经元评分、敲击速率、镜像运动、痉挛评估、认知筛查和假性球麻痹评估在内的全面临床评估。来自108名健康对照者的纵向神经影像学数据用于图像解读。实施了标准化成像方案，包括三维T1加权结构成像、扩散张量成像和静息态功能磁共振成像。在进行躯体定位分割后，进行皮质厚度分析、概率性纤维束成像、血氧水平依赖信号分析和脑干容积测定，以横断面和纵向评估皮质、脑干、皮质延髓和半球间的连接改变。
我们的数据证实了PLS患者存在进行性初级运动皮层变性、明显的辅助运动区和运动前区受累、进行性脑干萎缩、皮质延髓和半球间失联，以及临床上下运动神经元评分与躯体定位连接指数之间的密切关联。
原发性侧索硬化症与持续进展的运动连接组变性有关。PLS的临床残疾可能源于半球内和半球间连接下降以及初级、运动前区和辅助运动皮层变性的综合作用。简单的“床边”临床工具，如敲击速率，是对侧皮质脊髓束相关纤维完整性的良好替代指标。
