Reinnervation as measured by the motor unit size index is associated with preservation of muscle strength in amyotrophic lateral sclerosis, but not all muscles reinnervate

Abstract

Introduction/Aims: The motor unit size index (MUSIX) may provide insight into reinnervation patterns in diseases such as amyotrophic lateral sclerosis (ALS). However, it is not known whether MUSIX detects clinically relevant changes in reinnervation, or if all muscles manifest changes in MUSIX in response to reinnervation after motor unit loss.Methods: Fifty-seven patients with ALS were assessed at 3-month intervals for 12 months in four centers. Muscles examined were abductor pollicis brevis, abductor digiti minimi, biceps brachii, and tibialis anterior. Results were split into two groups: muscles with increases in MUSIX and those without increases. Longitudinal changes in MUSIX, motor unit number index (MUNIX), compound muscle action potential amplitude, and Medical Research Council strength score were investigated.Results: One hundred thirty-three muscles were examined. Fifty-nine percent of the muscles exhibited an increase in MUSIX during the study. Muscles with MUSIX increases lost more motor units (58% decline in MUNIX at 12 months, P < .001) than muscles that did not increase MUSIX (34.6% decline in MUNIX at 12 months, P < .001). However, longitudinal changes in muscle strength were similar. When motor unit loss was similar, the absence of a MUSIX increase was associated with a significantly greater loss of muscle strength (P = .002).

Maximising the translational potential of neurophysiology in amyotrophic lateral sclerosis: a study on compound muscle action potentials

“…Studies in which ALS patients were not age and gender matched with healthy controls were excluded. For longitudinal data studies, CMAP values were required up to and including 12 months [25][26][27][28][29][30] .…”

Label-free fibre optic Raman spectroscopy with bounded simplex-structured matrix factorization for the serial study of serum in amyotrophic lateral sclerosis

“…Several reports utilising more traditional techniques for monitoring ALS (such electrophysiological and imaging studies) have demonstrated significant changes in disease state within 4 months. 2,3 The most promising serum biomarker at present is NfL, a structural protein found in axons which is released when axons degenerate. Recent multi-centre work from the AMBRoSIA study group found that levels increased over time and modelling its inclusion as a trial outcome measure reduced sample size requirements.…”

“…Development of biomarkers of disease that can identify early changes are therefore a priority area of ALS research. Recent imaging, 2 electrophysiological 3 and serum [4][5][6] biomarker studies have demonstrated early changes in longitudinal measurements (within 3-6 months) with the potential to improve clinical trial design. 7 Raman spectroscopy is a form of vibrational spectroscopy based upon the inelastic scattering of light.…”

EMG Signs of Motor Units’ Enlargement in Stroke Survivors

“…Assessing muscle reinnervation progress remains fundamental to comprehending factors that promote and hinder illness recovery. The muscle reinnervation process has been associated with the preservation of muscle strength [14]. On the other hand, the motor units' enlargement may impair the ability of a reinnervated muscle to produce force increments as finely as healthy muscles since a greater amount of muscle fibers innervated by motoneurons would be activated for similar synaptic inputs [15].…”

“…Different methods involving incremental electrical stimulation, such as the "motor unit number estimation-MUNE" [18], the "electrophysiological muscle scan" [19], and the "motor unit size index-MUSIX" [14], have been proposed to indirectly assess structural adaptations on the neuromuscular system. The incremental stimulation technique gradually increases the stimulus intensity applied to a peripheral nerve to recruit successive motor units [18].…”