Service de neurologie, centre de référence maladies rares SLA et autres maladies du neurone moteur, CHU de Limoges, Limoges, France; Inserm, IRD, U1094 Tropical Neuroepidemiology, Institute of Epidemiology and Tropical Neurology, GEIST, université de Limoges, CHU de Limoges, Limoges, France; Fédération des Centres SLA de Limoges et Tours, Litorals, Limoges, France.
Service de neurologie, centre de référence maladies rares SLA et autres maladies du neurone moteur, CHU de Limoges, Limoges, France; Fédération des Centres SLA de Limoges et Tours, Litorals, Limoges, France.
Rev Neurol (Paris). 2021 May;177(5):536-543. doi: 10.1016/j.neurol.2021.03.001. Epub 2021 Apr 24.
Clinically, ALS phenotypes depend on the areas of the body that are affected, the different degrees of involvement of upper and lower motor neurons, the degrees of involvement of other systems, particularly cognition and behavior, and rates of progression. Phenotypic variability of ALS is characteristic and can be declined on the distribution of motor manifestations but also on the presence of extra-motor signs present in a variable manner in ALS patients. Neuropathologically, ALS is defined by the loss of UMN and LMN and the presence of two representative motor neuronal cytoplasmic inclusions, Bunina bodies and 43kDa Transactivation Response DNA Binding Protein (TDP-43) - positive cytoplasmic inclusions. The distribution of cytopathology and neuronal loss in patients is variable and this variability is directly related to phenotypic variability. Key regulators of phenotypic variability in ALS have not been determined. The functional decrement of TDP-43, and region-specific neuronal susceptibility to ALS, may be involved. Due to the selective vulnerability among different neuronal systems, lesions are multicentric, region-oriented, and progress at different rates. They may vary from patient to patient, which may be linked to the clinicopathological variability across patients.
临床上，ALS 的表型取决于受影响的身体部位、上下运动神经元受累的不同程度、其他系统（特别是认知和行为）受累的程度以及进展速度。ALS 的表型变异性是特征性的，可以根据运动表现的分布来描述，也可以根据 ALS 患者中以不同方式存在的运动外征象来描述。神经病理学上，ALS 定义为 UMN 和 LMN 的丧失，以及两种代表性的运动神经元细胞质内含物的存在，Bunina 体和 43kDa 反式激活反应 DNA 结合蛋白（TDP-43）阳性细胞质内含物。患者的细胞病理学和神经元丧失的分布是可变的，这种可变性与表型变异性直接相关。尚未确定 ALS 表型变异性的关键调节因子。TDP-43 的功能减退和 ALS 对特定神经元的易感性可能与之相关。由于不同神经元系统之间存在选择性易损性，病变呈多中心、区域定向，并且以不同的速度进展。它们可能因患者而异，这可能与患者之间的临床病理变异性有关。
