University of Leuven, Department of Neurosciences, Laboratory for Neurobiology, Vesalius Research Center, Box 912, B-3000 Leuven, Belgium.
Nat Rev Neurol. 2014 Nov;10(11):661-70. doi: 10.1038/nrneurol.2014.184. Epub 2014 Oct 14.
Classic textbook neurology teaches that amyotrophic lateral sclerosis (ALS) is a degenerative disease that selectively affects upper and lower motor neurons and is fatal 3-5 years after onset--a description which suggests that the clinical presentation of ALS is very homogenous. However, clinical and postmortem observations, as well as genetic studies, demonstrate that there is considerable variability in the phenotypic expression of ALS. Here, we review the phenotypic variability of ALS and how it is reflected in familial and sporadic ALS, in the degree of upper and lower motor neuron involvement, in motor and extramotor involvement, and in the spectrum of ALS and frontotemporal dementia. Furthermore, we discuss some unusual clinical characteristics regarding presentation, age at onset and disease progression. Finally, we address the importance of this variability for understanding the pathogenesis of ALS and for the development of therapeutic strategies.
经典的神经科教科书告诉我们，肌萎缩侧索硬化症（ALS）是一种退行性疾病，选择性地影响上下运动神经元，发病后 3-5 年内致命——这一描述表明 ALS 的临床表现非常同质。然而，临床和尸检观察以及遗传研究表明，ALS 的表型表达存在相当大的可变性。在这里，我们回顾了 ALS 的表型变异性，以及它在家族性和散发性 ALS 中、在上运动神经元和下运动神经元受累程度、在运动和非运动受累中的表现，以及在 ALS 和额颞叶痴呆的范围内的表现。此外，我们还讨论了一些关于发病、发病年龄和疾病进展的不寻常的临床特征。最后，我们讨论了这种变异性对理解 ALS 的发病机制和治疗策略的重要性。
