First-recruited motor units adopt a faster phenotype in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with a median survival of three years. We employed serial high-density surface EMG (HDSEMG) to characterise 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 minutes of resting muscle and 1 minute 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, afterhyperpolarisation 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 (82.7ms) than strong ALS muscles (96.0ms; p=0.00919) and BFS muscles (95.3ms; p=0.0039). Mean MU potential area (area-under-the-curve: 487.5 vs. 98.7μV ms; p<0.0001) and muscle fibre conduction velocity (6.2 vs. 5.1m/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. 232.4μV ms; p=0.00144). These results suggest that first-recruited MUs develop a faster phenotype in latter stages of ALS, likely driven by the preferential loss of vulnerable fast-twitch motor units. Inhibition of this potentially maladaptive phenotypic drift may protect the longevity of the motor unit pool, stimulating a novel therapeutic avenue.