A novel clinically available motor unit estimation method (MUNE) referred to as the MScanFit (Bostock, 2016) shows promise in tracking the progression of amyotrophic lateral sclerosis (ALS). We aimed to investigate whether changes in motor axon excitability in ALS affect MScanFit.

The drop in compound motor action potential amplitude underestimates the extent of motor unit loss in ALS due to collateral sprouting of the surviving motor units. MUNE by MScanFit models the full stimulus-response curve referred to as a muscle scan (MScan). Each modeled motor unit amplitude, threshold (t) and threshold variability (SD) parameters are programmatically optimized to reduce the error between the modeled and the recorded MScans for a varying number of motor units, until the best fit is reached. To reduce the programmatic complexity and speed-up the model fitting MScanFit assumes the relative spread (RS) of threshold (SD(t)/t x100) to be constant among motor units.

The RS was determined to be about 2% in motor axons with normal excitability. Here we explored whether the same RS is suitable to assess the MScanFit in ALS patients as well as in a commonly used ALS mouse model (male SOD1G93A, high copy number). In humans, MScans were recorded from the thenar muscles following stimulation of the median nerve at wrist. In mice, MScans were recorded from the plantar muscles following stimulation of the tibial nerve at ankle under Ketamine – Xylazine anaesthesia.

We found that RS was increased in ALS patients as compared to controls. The RS increase correlated with disease progression up to 22 weeks of age in SOD1G93 mice.

Our data suggest that RS is increased in ALS consistent with theoretical expectations for increased motor axon excitability. Accounting for changes in RS could improve the value of MScanFit MUNE in ALS.

Bostock H. Muscle Nerve 2016;53:889-896