JNNP:脑MRI和神经系统检查对肌萎缩侧索硬化症患者上运动神经元变性的敏感性

2021-10-20 MedSci原创 MedSci原创

脊髓或脑干下部运动神经元(LMN)以及上部运动神经元(UMN)和额颞部大脑病理学的异质性决定了肌萎缩侧索硬化(ALS)患者的临床变异性,并使疾病进展的早期诊断和测量复杂化。

脊髓或脑干下部运动神经元(LMN)以及上部运动神经元(UMN)和额颞部大脑病理学的异质性决定了肌萎缩侧索硬化(ALS)患者的临床变异性,并使疾病进展的早期诊断和测量复杂化。在临床上,LMN临床特征得到了肌电图结果的支持,在后续研究中可能比UMN体征更容易检测和客观量化,因为UMN临床特征可能在LMN严重受累的肢体中被隐藏。

在临床研究中,如确定ALS有效治疗的试验,修订后的ALS功能评定量表(ALSFRS-R)用于测量功能衰退。然而,ALSFRS-R项目对LMN体征特别敏感,这意味着临床试验可能无法测量UMN治疗效果。因此,UMN退变的生物标记物可提高临床试验的敏感性和效力。大脑MRI测量,如运动皮质厚度(CT)和锥体束纤维密度可用于评估ALS患者的灰质和白质变性,而经颅磁刺激(TMS)提供对UMN功能的活体洞察。横截面研究表明UMN体征与灰色和白色物质变性之间存在关系;然而,之前尚未进行UMN体征和大脑MRI敏感性的纵向比较。意识到脑MRI在临床研究中作为UMN生物标记物的可能性,本文使用纵向多模式脑成像和神经学检查来研究哪种测量方法对ALS中的UMN变性更敏感。本文发表在《神经病学,神经外科学和精神病学杂志》上(

招募了678名受试者。选择至少两次随访的患者,排除136名仅随访一次的患者。排除了36名患有正呼吸、幽闭恐怖症或脑结构异常(即脑瘤、中风)的参与者,研究人群为506人(192名患者;314名对照)。参与者给予书面知情同意。所有患者均以4-6分就诊两次 每隔一个月。在两次就诊中, 对五个身体区域(延髓区和四肢)进行了神经学检查,以确定是否存在UMN和LMN体征。

本实验研究设计

健康对照组的受试者也接受了神经学检查,以确定他们中没有人有可能混淆结果的UMN症状。每个检查者使用一个标准化方案,该方案源自运动神经元疾病(MND)专家中心的神经系统检查。在10年的研究期间,平均每年有三名检查者进行神经系统检查。除神经系统检查外,评估了临床特征、22种功能状态以及认知和行为状态并使用3T Philips(Philips Medical Systems,Best,荷兰)Achieve医疗仪获取了大脑的高分辨率T1加权和扩散加权图像(DWI)。根据五个身体区域的受累情况将患者分为三类:两次就诊时均无或微量UMN征象的患者(稳定的无/微量UMN征象)、两次就诊之间进展为中度或重度UMN征象的患者(进行性UMN征象)以及两次就诊时均为中度或重度UMN的患者(稳定的中度/重度UMN体征)。

运动皮质变薄的模式。运动皮质被分成每个半球30个部分,测量对照组(n=314)和ALS患者(n=192)之间的差异

使用运动CT和锥体束纤维密度作为UMN退变的指标(即,皮质厚度和纤维密度越低,UMN退化越严重)。为了获得锥体束纤维密度,我们将DWI数据记录到T1数据中,并使用FSL(V.6.0)校正运动、涡流和磁化率失真。使用横截面和纵向数据,根据运动皮质和锥体束的躯体结构,描述了ALS对大脑UMN的影响。 根据第一次和第二次就诊时的UMN征象,通过比较第一次就诊时不同类别大脑MRI的区域运动CT和锥体束纤维密度,检查了在UMN征象变得临床明显之前,大脑MRI是否显示UMN变性。进行了三次敏感性分析。比较运动CT、纤维密度和临床UMN特征作为UMN变性的生物标志物。

运动CT和纤维密度测量的平均UMN退变在随后的分类中恶化。对于运动CT,每个比较都是显著的;对于纤维密度,与对照组的每一项比较都是显著的。随着时间的推移,从健康阶段到身体某一区域的严重UMN体征,平均UMN退化。首次就诊时,这些患者的运动CT与归类为延髓区和左腿UMN征象进展的患者有显著差异。这些患者的运动CT和纤维密度与球区被归类为稳定的中度或重度UMN征象的患者以及双腿的运动CT患者有显著差异。比较了运动CT的进展、纤维密度和UMN体征随时间的变化,发现运动CT的标准化斜率比UMN Devine评分的斜率更陡,左臂除外。发现所有身体部位的运动皮质都在进行性变薄。延髓区和左臂的UMN体征进展显著。对于每个身体部位,除右腿外,临床UMN体征的标准化斜率比纤维密度的斜率更陡,对于延髓区和左臂是显著的。

运动CT是一种比UMN特征更敏感的UMN退变测量方法。运动CT和锥体束FD在患者和对照组之间有区别。脑MRI可以在症状变得明显之前监测UMN退变。研究结果促使MRI成为ALS临床试验中UMN进展的潜在生物标志物。

Nitert ADTan HHWalhout R, et al Sensitivity of brain MRI and neurological examination for detection of upper motor neurone degeneration in amyotrophic lateral sclerosis

 

 

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    2022-09-14 chendoc252
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    2021-10-21 huangdf
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