Clinical Spectrum of Amyotrophic Lateral Sclerosis (ALS)
Clinical Spectrum of Amyotrophic Lateral Sclerosis (ALS)
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DOI：
10.1101/cshperspect.a024117
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发表时间：
2017-08-01
影响因子：
5.4
通讯作者：
Cashman, Neil R.
中科院分区：
文献类型：
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作者：
Grad, Leslie I.;Rouleau, Guy A.;Cashman, Neil R.
肌萎缩侧索硬化症（ALS）的主要特征是运动神经元的进行性丧失，尽管在病例之间存在显著的表型异质性。典型的或“经典的”ALS与疾病发作时同时累及上运动神经元（UMN）和下运动神经元（LMN）相关，而非典型形式，如原发性侧索硬化和进行性肌萎缩，分别在UMN和LMN中具有早期和主要的累及。不同的表型可以如此独特，以至于它们似乎具有不同的生物学。由于相同的表型可能有多种原因，包括不同的基因突变，可能有多种分子机制导致ALS，这意味着该疾病是一种综合征。相反，多种表型可由单个基因突变引起;因此，单个分子机制可与临床异质性相容。ALS的致病机制尚不清楚，但病理学在神经解剖学上的主动传播可能是主要组成部分。
Amyotrophic lateral sclerosis (ALS) is primarily characterized by progressive loss of motor neurons, although there is marked phenotypic heterogeneity between cases. Typical, or "classical," ALS is associated with simultaneous upper motor neuron (UMN) and lower motor neuron (LMN) involvement at disease onset, whereas atypical forms, such as primary lateral sclerosis and progressive muscular atrophy, have early and predominant involvement in the UMN and LMN, respectively. The varying phenotypes can be so distinctive that they would seem to have differing biology. Because the same phenotypes can have multiple causes, including different gene mutations, there may be multiple molecular mechanisms causing ALS, implying that the disease is a syndrome. Conversely, multiple phenotypes can be caused by a single gene mutation; thus, a single molecular mechanism could be compatible with clinical heterogeneity. The pathogenic mechanism(s) in ALS remain unknown, but active propagation of the pathology neuroanatomically is likely a primary component.