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• Surface electromyography (sEMG) signals from upper extremity muscles are recorded in 31 patients with spinal muscular atrophy (SMA) treated with pyridostigmine. • sEMG signal frequency and amplitude dynamics reveal enhanced low-threshold motor unit (LT MU) capacity during execution of endurance tasks in individual patients. • Ameliorating LT MU function is a potential therapeutic target to reduce fatigability in SMA. To investigate the electrophysiological basis of pyridostigmine enhancement of endurance performance documented earlier in patients with spinal muscular atrophy (SMA). We recorded surface electromyography (sEMG) in four upper extremity muscles of 31 patients with SMA types 2 and 3 performing endurance shuttle tests (EST) and maximal voluntary contraction (MVC) measurements during a randomized, double blind, cross-over, phase II trial. Linear mixed effect models (LMM) were used to assess the effect of pyridostigmine on (i) time courses of median frequencies and of root mean square (RMS) amplitudes of sEMG signals and (ii) maximal RMS amplitudes during MVC measurements. These sEMG changes over time indicate levels of peripheral muscle fatigue and recruitment of new motor units, respectively. In comparison to a placebo, patients with SMA using pyridostigmine had fourfold smaller decreases in frequency and twofold smaller increases in amplitudes of sEMG signals in some muscles, recorded during ESTs (p < 0.05). We found no effect of pyridostigmine on MVC RMS amplitudes. sEMG parameters indicate enhanced low-threshold (LT) motor unit (MU) function in upper-extremity muscles of patients with SMA treated with pyridostigmine. This may underlie their improved endurance. Our results suggest that enhancing LT MU function may constitute a therapeutic strategy to reduce fatigability in patients with SMA. [ABSTRACT FROM AUTHOR]

• Compound muscle action potential scan-derived markers are sensitive to track disease progression in amyotrophic lateral sclerosis. • Motor unit number estimation was most sensitive and may increase efficiency of clinical trials compared to clinical endpoints. • Standardization of compound muscle action potential scans can further maximize its utility for clinical use and research. To determine which compound muscle action potential (CMAP) scan-derived electrophysiological markers are most sensitive for monitoring disease progression in amyotrophic lateral sclerosis (ALS), and whether they hold value for clinical trials. We used four independent patient cohorts to assess longitudinal patterns of a comprehensive set of electrophysiological markers including their association with the ALS functional rating scale (ALSFRS-R). Results were translated to trial sample size requirements. In 65 patients, 225 thenar CMAP scan recordings were obtained. Electrophysiological markers showed extensive variation in their longitudinal trajectories. Expressed as standard deviations per month, motor unit number estimation (MUNE) values declined by 0.09 (CI 0.07–0.12), D50, a measure that quantifies CMAP scan discontinuities, declined by 0.09 (CI 0.06–0.13) and maximum CMAP by 0.05 (CI 0.03–0.08). ALSFRS-R declined fastest (0.12, CI 0.08 – 0.15), however the between-patient variability was larger compared to electrophysiological markers, resulting in larger sample sizes. MUNE reduced the sample size by 19.1% (n = 388 vs n = 314) for a 6-month study compared to the ALSFRS-R. CMAP scan-derived markers show promise in monitoring disease progression in ALS patients, where MUNE may be its most suitable derivate. MUNE may increase clinical trial efficiency compared to clinical endpoints. [ABSTRACT FROM AUTHOR]

• Surface EMG signals from extremity muscles are recorded in a large cohort (n = 70) of spinal muscular atrophy (SMA) patients. • EMG signal amplitude during endurance testing is strongly inversely correlated to SMA phenotype, e.g. the highest amplitudes in SMA type 2. • Individual patients with SMA show motor unit reserve capacity providing a target for pharmacological and/or exercise therapy. To investigate the availability of any motor unit reserve capacity during fatiguing endurance testing in patients with spinal muscular atrophy (SMA). We recorded surface electromyography (sEMG) of various muscles of upper- and lower extremities of 70 patients with SMA types 2–4 and 19 healthy controls performing endurance shuttle tests (ESTs) of arm and legs. We quantitatively evaluated the development of fatigability and motor unit recruitment using time courses of median frequencies and amplitudes of sEMG signals. Linear mixed effect statistical models were used to evaluate group differences in median frequency and normalized amplitude at onset and its time course. Normalized sEMG amplitudes at onset of upper body ESTs were significantly higher in patients compared to controls, yet submaximal when related to maximal voluntary contractions, and showed an inverse correlation to SMA phenotype. sEMG median frequencies decreased and amplitudes increased in various muscles during execution of ESTs in patients and controls. Decreasing median frequencies and increasing amplitudes reveal motor unit reserve capacity in individual SMA patients during ESTs at submaximal performance intensities. Preserving, if not expanding motor unit reserve capacity may present a potential therapeutic target in clinical care to reduce fatigability in individual patients with SMA. [ABSTRACT FROM AUTHOR]