Amyotrophic lateral sclerosis: an update
Amyotrophic lateral sclerosis: an update
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DOI：
10.1097/wco.0b013e32834916a9
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发表时间：
2011-10-01
影响因子：
4.8
通讯作者：
Swash, Michael
中科院分区：
文献类型：
--
作者：
de Carvalho, Mamede;Swash, Michael
综述的目的目的是回顾肌萎缩侧索硬化症（ALS）的最新出版物。最近的发现淡路推荐的电生理诊断将允许早期临床试验进入。使用超声波来观察肌束震颤，即使是在深层肌肉中，也将有助于早期诊断。不幸的是，最近在ALS中的临床试验令人失望，如负锂试验所示。新的、更便宜的试验设计和在ALS病程早期纳入患者是未来试验的积极方法。对ALS生物标志物的研究仍在继续，一些令人鼓舞的报告已经发表，但还没有ALS特有的特征改变了这一领域。ALS最令人兴奋的进展来自蛋白质研究和遗传学。在散发性ALS以及一些额颞叶痴呆（FTD）患者中，泛素化的胞质内含物含有TDP-43，并且一些家族性病例（和少数散发病例）具有TDP-43基因突变，这一认识已经改变了以前关于ALS发病机制的概念。其他新发现的与ALS相关的突变，如融合肉瘤（FUS）和含valosin-containing蛋白（VCP），不仅拓宽了ALS相关基因的谱，而且巩固了ALS和FTD之间的密切关系。然而，一个持续的困难是早期临床诊断，特别是需要鉴定对疾病过程中的临床变化敏感的独特生物标志物。
Purpose of reviewThe aim is to review recent publications on amyotrophic lateral sclerosis (ALS).Recent findingsThe Awaji recommendations for electrophysiological diagnosis will permit earlier clinical trials entry. The use of ultrasound to visualize fasciculations, even in deep muscles, will contribute to earlier diagnosis, as well. Unfortunately, recent clinical trials in ALS have been disappointing, as illustrated by the negative lithium trials. New, less expensive, trial designs and the inclusion of patients early in the course of ALS are positive approaches for future trials. The search for ALS biomarkers continues and a number of encouraging reports have been published, but no features unique to ALS have yet transformed this field. The most exciting advances in ALS arise from protein studies and genetics. Recognition that the ubiquitinated cytosolic inclusions in sporadic ALS, as well as in some patients with frontotemporal dementia (FTD), contain TDP-43, and that some familial cases (and a few sporadic cases) have mutations of the TDP-43 gene has transformed previous concepts on ALS pathogenesis. Other newly recognized mutations linked to ALS, such as fused-in-sarcoma (FUS) and valosin-containing protein (VCP), have not only widened the spectrum of genes involved in ALS but also consolidated the close relation between ALS and FTD.SummaryALS research is entering a new phase that should generate new proposals regarding putative therapies, or strategies for disease treatment. A continuing difficulty, however, is early clinical diagnosis and, especially, the need for identification of a unique biomarker, sensitive to clinical change in the course of the disease.