UK Dementia Research Institute, Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Department of Bioengineering, Imperial College London, London, UK.
J Physiol. 2021 Sep;599(17):4117-4130. doi: 10.1113/JP281310. Epub 2021 Aug 9.
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder of motor neurons, carrying a short survival. High-density motor unit recordings permit analysis of motor unit size (amplitude) and firing behaviour (afterhyperpolarization duration and muscle fibre conduction velocity). Serial recordings from biceps brachii indicated that motor units fired faster and with greater amplitude as disease progressed. First-recruited motor units in the latter stages of ALS developed characteristics akin to fast-twitch motor units, possibly as a compensatory mechanism for the selective loss of this motor unit subset. This process may become maladaptive, highlighting a novel therapeutic target to reduce motor unit vulnerability.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with a median survival of 3 years. We employed serial high-density surface electromyography (HDSEMG) to characterize voluntary and ectopic patterns of motor unit (MU) firing at different stages of disease. By distinguishing MU subtypes with variable vulnerability to disease, we aimed to evaluate compensatory neuronal adaptations that accompany disease progression. Twenty patients with ALS and five patients with benign fasciculation syndrome (BFS) underwent 1-7 assessments each. HDSEMG measurements comprised 30 min of resting muscle and 1 min of light voluntary activity from biceps brachii bilaterally. MU decomposition was performed by the progressive FastICA peel-off technique. Inter-spike interval, firing pattern, MU potential area, afterhyperpolarization duration and muscle fibre conduction velocity were determined. In total, 373 MUs (ALS = 287; BFS = 86) were identified from 182 recordings. Weak ALS muscles demonstrated a lower mean inter-spike interval (82.7 ms) than strong ALS muscles (96.0 ms; P = 0.00919) and BFS muscles (95.3 ms; P = 0.0039). Mean MU potential area (area under the curve: 487.5 vs. 98.7 μV ms; P < 0.0001) and muscle fibre conduction velocity (6.2 vs. 5.1 m/s; P = 0.0292) were greater in weak ALS muscles than in BFS muscles. Purely fasciculating MUs had a greater mean MU potential area than MUs also under voluntary command (area under the curve: 679.6 vs. 232.4 μV ms; P = 0.00144). These results suggest that first-recruited MUs develop a faster phenotype in the latter stages of ALS, likely driven by the preferential loss of vulnerable fast-twitch MUs. Inhibition of this potentially maladaptive phenotypic drift may protect the longevity of the MU pool, stimulating a novel therapeutic avenue.
肌萎缩侧索硬化症（ALS）是一种不可治愈的运动神经元神经退行性疾病，患者生存时间较短。高密度运动单元记录允许分析运动单元的大小（幅度）和放电行为（后超极化持续时间和肌纤维传导速度）。肱二头肌的连续记录表明，随着疾病的进展，运动单元的放电速度更快，幅度更大。在 ALS 的后期阶段，首先募集的运动单元表现出类似于快肌运动单元的特征，这可能是对这种运动单元亚群选择性丧失的一种补偿机制。这个过程可能变得适应不良，突出了一个新的治疗靶点，以降低运动单元的脆弱性。
肌萎缩侧索硬化症（ALS）是一种进行性神经退行性疾病，中位生存时间为 3 年。我们采用连续高密度表面肌电图（HDSEMG）在疾病的不同阶段描述自愿和异位运动单元（MU）放电模式。通过区分对疾病具有不同易感性的 MU 亚型，我们旨在评估伴随疾病进展的代偿性神经元适应。20 名 ALS 患者和 5 名良性肌束震颤综合征（BFS）患者每人接受了 1-7 次评估。HDSEMG 测量包括双侧肱二头肌 30 分钟的休息肌肉和 1 分钟的轻度自愿活动。MU 分解采用渐进式 FastICA 剥落技术完成。测定峰间间隔、放电模式、MU 潜能面积、后超极化持续时间和肌纤维传导速度。总共从 182 次记录中识别出 373 个 MU（ALS=287；BFS=86）。弱 ALS 肌肉的平均峰间间隔（82.7ms）低于强 ALS 肌肉（96.0ms；P=0.00919）和 BFS 肌肉（95.3ms；P=0.0039）。弱 ALS 肌肉的 MU 潜在面积（曲线下面积：487.5 与 98.7μVms；P<0.0001）和肌纤维传导速度（6.2 与 5.1m/s；P=0.0292）均大于 BFS 肌肉。纯粹肌束震颤的 MU 的 MU 潜在面积大于也受自愿支配的 MU（曲线下面积：679.6 与 232.4μVms；P=0.00144）。这些结果表明，在 ALS 的后期阶段，首先募集的 MU 表现出更快的表型，可能是由易损的快肌 MU 优先丧失驱动的。抑制这种潜在的适应不良的表型漂移可能会保护 MU 池的寿命，从而刺激新的治疗途径。
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