Selective Muscle Involvement in Amyotrophic Lateral Sclerosis: Evidence Inferred from the Point of Motor Unit Firing Rates

Abstract

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. Motor-evoked 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.

Keywords: Amyotrophic lateral sclerosis; firing rate; motor unit potential; transcranial magnetic stimulation; triple stimulation technique.

Figure 1

Two consecutive motor unit pairs recorded in a control (left) and a patient with ALS (right). First row (I): Multi-MUP software showing the two consecutive motor units with different amplitude, duration, phase and turn numbers in a control (1,2) and a patient with ALS (3,4). Note the relatively stable muscle contraction with only slight physiological variations in the inter-discharge intervals of each motor unit (arrow). Second (II) and third (III) rows: Each MUP was shown triggered and rastered in 20 lines in different windows. The sweep duration was re-arranged to view the triggering and jittering MUPs in the same line. Vertical lines indicate the maximum and minimum interpotential intervals and the difference between them depicted by ‘a’ (‘a’ values for each MUP; a1, a2, a3, a4). Note the higher ‘a’ values in ALS and the increased variability of motor unit firing rate.

Figure 2

Quantitative MUP, firing rate and recruitment properties in patients with ALS (blue) and controls (green). Motor unit potential amplitudes were higher and MUP durations were longer in patients with ALS when compared with controls (p≤0.001). Note the increased phase and turn number of Del MUPs in patients with ALS compared with the controls (p≤0.001) and the increased turn number of Del MUPs compared with those of FDI in patients with ALS (p=0.006). The FR, MCD, and FRV of MUPs were higher in patients with ALS than those of the controls (p≤0.001). Also note the higher FR and MCD of FDI, and the lower FRV of Del in patients with ALS. * indicates to significant differences between (group) subject factors, ¥ indicates to significant differences within (muscle) subject factors (A-Del vs ADM and FDI, D-Del vs FDI, E-FDI vs ADM, F-FDI vs ADM and Del, G– Del vs ADM and FDI).