Investigate motor unit action potential (MUAP) amplitudes in adults with Spinal Muscular Atrophy (SMA).

SMA is an inherited motor neuron disorder caused by reduced SMN protein that results in progressive motor neuron death, loss of MUs, and muscle weakness.  MU enlargement via collateral sprouting is a mechanism by which the MU pool can compensate for motor neuron loss. In this study, we aimed to investigate the relationship between MUAP amplitudes and disease severity in SMA.

Adults with genetically-confirmed SMA and healthy controls were enrolled. MUAPs were decomposed from multi-electrode surface recordings during a 30-second maximum contraction of the abductor digiti minimi muscle. MUAPs amplitudes were compared between groups based on ambulatory status and by K-means cluster analyses of Revised Upper Limb Module (RULM) score. 

Seven ambulatory (40 ± 7 years, 42.9% female, 26 MUs), 9 non-ambulatory (40 ± 14 years, 55.6% female, 54 MUs), and 8 control (40 ± 11 years, 50.0% female, 54 MUs) participants were enrolled. SMA patients all received nusinersen, mean duration: 22.25 months (range 10-30). MUAPs were significantly smaller in non-ambulatory SMA versus ambulatory SMA but not controls (p<0.0001, p=0.0508, respectively). Conversely, MUAPs were larger in ambulatory SMA versus controls (p=0.0136). K-cluster analysis identified 3 RULM clusters: low, high, and intermediate; the low and high clusters showed MUAPs were altered versus controls (reduced and increased, respectively); MUAPs were similar in the intermediate RULM cluster and controls.

Functional status in SMA appears to be associated with differing capacities for MU remodeling. This has implications for potential outcomes when receiving disease-modifying treatment and simple classification based on ambulatory status may be insufficient for understanding treatment responses. Future work should investigate factors influencing this differential collateral sprouting capacity.  Improving collateral sprouting may be a possible therapeutic avenue in SMA.