Selective muscle involvement in amyotrophic lateral sclerosis: Evidence inferred from the point of motor unit firing rates

Clinical and electromyographic abnormalities are generally more prominent in distal muscles ('distal-proximal gradient' )(1-3) and on the lateral side of the hand ('lateral-medial gradient' )(4,5) in patients with amyotrophic lateral sclerosis (ALS).However, the role of upper motor neuron (UMN) or lower motor neuron (LMN) dysfunction as the promoter of these phenomena is still debated.Motor unit firing and recruitment are essential for the graded tuning of the force exerted by voluntary muscle contraction (6).Motor units are recruited in an orderly fashion and to do so, spinal motor neurons need synaptic inputs from descending projections, spinal interneurons, and sensory afferents (7,8).Firing rate and recruitment properties of motor units (MU) could give indirect information about how these synaptic inputs and the spinal motor neurons themselves function both in health and disease (9,10).Introduction: The aim of the study is to determine the role of upper motor neuron (UMN) or lower motor neuron (LMN) dysfunction as the primary initiator of distal-proximal and lateral-medial gradients of muscle involvement in amyotrophic lateral sclerosis (ALS).Methods: Concentric needle electromyography recordings were performed in deltoid, abductor digiti minimi, and first dorsal interosseous (FDI) muscles in patients with ALS and controls during slight voluntary contraction needed to activate two motor units (MU).Five motor unit potential (MUP) pairs were recorded from each muscle.Motor unit potential analyses were performed offline using Multi-MUP analysis program.Quantitative MUP parameters, MU firing rate (FR), FR variability (FRV), and mean consecutive difference (MCD) were calculated.Motorevoked potentials and the triple stimulation technique (TST) were performed to evaluate UMN involvement.Results: Twenty patients with ALS along with 20 age and sex-matched healthy volunteers were enrolled.Quantitative MUP parameters compatible with denervation and reinnervation were found in patients with ALS, who also showed higher FR, FRV, and MCD values, most prominently in FDI.First dorsal interosseous FRV was lower in patients with abnormal central motor conduction time (CMCT).Firing rate and FRV were negatively correlated with CMCT, but not with TST.Conclusion: Distal limb muscles, particularly FDI, revealed more prominent FR abnormalities in patients with ALS in parallel with the distal-proximal and lateral-medial gradients of the selective muscle involvement pattern which seems predominantly to be correlated with LMN dysfunction.Reduced FRV may be associated with the presence of UMN dysfunction in ALS.