Neurology:渐冻人,皮质过度兴奋或与TDP-43的积累有关

2021-04-24 Freeman MedSci原创

渐冻人,皮质过度兴奋或与TDP-43的积累有关

 

肌萎缩性脊髓侧索硬化症(ALS),即“渐冻症”,是一种异质性的多系统神经退行性疾病,以上下运动神经元功能障碍为特征。虽然主要被认为是一种进行性的运动功能紊乱,但认知和行为异常也越来越被认为是ALS的一个临床特征。

虽然5-15%的ALS患者可能会出现额颞叶痴呆的临床特征,但30-50%的ALS患者可能会出现更细微的认知和行为障碍。

在病理层面上,认知和行为异常的发展与运动外皮层区域过度磷酸化的TDP-43蛋白的积累有关。皮质过度兴奋已被报道为ALS的一个致病过程,与运动神经元变性、疾病演变和不良预后相关联。

抑制性皮质运动回路的退化与ALS的皮质过度兴奋性的出现有关。鉴于皮质过度兴奋性随着疾病的发展而增加,可以说TDP-43的积累可能介导了ALS中不断发展的生理异常。

爱丁堡认知和行为ALS筛查(ECAS)是作为评估ALS认知和行为功能的具体工具而开发的,提供了对ALS特定(执行功能、言语流畅性和语言)和非特定(回忆、识别记忆和视觉空间功能)认知领域的了解。

与此相关的是,ECAS得分似乎可以预测ALS的TDP-43病理。

鉴于认知功能障碍和皮质过度兴奋性随着疾病的发展而变得更加突出,悉尼大学的Mana Higashihara等人,探究了ALS中运动皮质兴奋性和认知障碍之间的关系。

他们使用经颅磁刺激(TMS)来评估皮质兴奋性,认知功能由爱丁堡认知和行为ALS筛查(ECAS)量表确定。认知障碍的定义是ECAS<105。

皮质过度兴奋的定义是短间隔皮质内抑制(SICI)减少,短间隔皮质内促进(SICF)增加,兴奋性指数(IE)和运动诱发电位(MEP)振幅。

他们纳入了40名ALS患者,其中36%有明显的认知障碍(23名男性,平均年龄62.1岁)。

认知障碍患者的皮质过度兴奋性更为突出,表现为短间隔皮质内促进(SICF)、兴奋性指数(IE)和运动诱发电位(MEP)振幅增加。

SICF与ECAS评分独立相关(β = 2.410;p < 0.05)。

SICI的降低在ALS中很明显,在执行分数降低的患者中更为突出。

这个新颖的研究,重要意义在于发现了,认知障碍的ALS患者的皮质过度兴奋性比对照组更突出。鉴于ECAS量表评分是TDP-43病理学的有效预测指标,皮质过度兴奋性的增加可能与TDP-43的积累有关。

原文出处:
https://n.neurology.org/content/96/16/e2090
Association of Cortical Hyperexcitability and Cognitive Impairment in Patients With Amyotrophic Lateral Sclerosis
Mana Higashihara, Nathan Pavey, et al.
Neurology Apr 2021, 96 (16) e2090-e2097; DOI: 10.1212/WNL.0000000000011798

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    2022-02-24 yinhl1978
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    2021-04-25 147b4a41m37暂无昵称

    挺好的

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    2021-04-24 ms2000001051330459

    学习了,涨知识了!

    0

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他,是一名农民工,为千家万户维护着电梯,守护着大家的安全。他,是上海劳模,敬岗爱业。直到有一天,自己连扳手都转不动时,才发现自己成了“渐冻人”。6年前,黄胜发曾在徐汇大华医院维护保养电梯。6年后的今天,大华医院用一种令人唏嘘的方式对他进行了“回报”:为这位身患绝症的市劳模免费进行了胃造瘘手术,让已经失去进食能力的他能继续活下去。全国优秀农民工、上海市劳动模范、上海五一劳动奖状……39岁的黄胜发