Martinelli Ilaria, Mandrioli Jessica, Ghezzi Andrea, Zucchi Elisabetta, Gianferrari Giulia, Simonini Cecilia, Cavallieri Francesco, Valzania Franco
Department of Neurosciences, Azienda Ospedaliero Universitaria di Modena, Modena, Italy.
Clinical and Experimental Medicine Ph.D. Program, University of Modena and Reggio Emilia, Modena, Italy.
Neural Regen Res. 2025 Jan 1;20(1):130-138. doi: 10.4103/NRR.NRR-D-23-01904. Epub 2024 Apr 3.
Amyotrophic lateral sclerosis (ALS) is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex, brainstem, and spinal cord. While the typical clinical phenotype of ALS involves both upper and lower motor neurons, human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions, expanding the phenotype of ALS. Although superoxide dismutase 1 (SOD1) mutations represent a minority of ALS cases, the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies. Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1 (SOD1-ALS), no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation. In this narrative review, we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS. The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms, pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.
肌萎缩侧索硬化症（ALS）是一种神经肌肉疾病，由皮质、脑干和脊髓中的运动神经元进行性退化所致。虽然ALS的典型临床表型涉及上、下运动神经元，但多年来的人体和动物研究强调了其可能扩散至其他运动和非运动区域，从而扩展了ALS的表型。尽管超氧化物歧化酶1（SOD1）突变仅占ALS病例的少数，但SOD1基因仍是ALS研究的一个里程碑，因为它是个性化治疗的首个基因靶点。尽管有许多单病例报告或病例系列显示，携带SOD1突变的ALS患者（SOD1-ALS）存在运动外症状，但尚无研究全面探讨该亚群中运动外神经表现的全貌。在这篇叙述性综述中，我们分析并讨论了有关SOD1-ALS期间锥体外系和非运动特征的现有文献。SOD1的多方面表达可能会加深我们对致病机制的理解，鉴于针对SOD1-ALS的新治疗策略，这为受影响患者指明了一种多学科方法。
