Standard and modified statistical mune evaluations in spinal‐bulbar muscular atrophy

Abstract

MUNE, a technique used in ALS clinical trials to quantitatively assess motor neuron loss, should also be valuable in assessing progression in spinal bulbar muscular atrophy (SBMA), an x-linked neuronopathy. In ALS, instability of single motor units (SMUP) prompted Shefner9 to modify the statistical MUNE method to exclude SMUPs ≤ 40μV. It is unknown if there is a similar SMUP instability in the more chronic degenerative disease of SBMA.In this study, the standard parameter of excluding SMUP < 10 μV was compared with the exclusion of SMUP < 40 μV in the calculation of the statistical MUNE. The mean statistical MUNE, using the standard method and the Shefner method, was 60±21 to 47±23, respectively. Similar to ALS, SBMA showed an increased proportion (17%) of individual SMUPs ≤ 40 μV compared to normal controls.In conclusion, excluding SMUPs ≤ 40 μV from the statistical MUNE calculations is appropriate for SBMA subjects because their SMUPs characteristics are similar to ALS. Exclusion of the low amplitude SMUPs reduces the calculated MUNE.

The profile of motor unit number estimation (MUNE) in spinal and bulbar muscular atrophy

“…MUNE values calculated by both the amplitude and the area methods were significantly lower in the patients with SBMA than those in normal controls (table 1), and were similar to a previous report 25. Patients with SBMA showed a lower maximum CMAP than normal controls, whereas the SMUP of patients with SBMA were higher than those of normal controls (table 1).…”

“…Muscle biopsies from patients with lower motor neuron disorders have showed a high terminal innervation ratio caused by the nodal sprouting 32. MUNE in motor neuron diseases has been shown to decrease generally,25 33–36 while the amplitude of SMUP varies according to specific disease properties. For example, SMUP has been reported to be elevated in SMA, which is characterised by a chronic degeneration of motor neurons similar to SBMA 33.…”

“…MUNE and muscular strength have been shown to be correlated in patients with motor neuron disease 24. There are, however, few reports on MUNE in SBMA 25. The aim of this study is to count the number of motor units in patients with SBMA, as well as to examine whether MUNE is a potential biomarker that reflects the pathophysiology and progression of motor neuron degeneration in this disease.…”

Efficacy and safety of dutasteride in patients with spinal and bulbar muscular atrophy: a randomised placebo-controlled trial

“…Nerve conduction studies were therefore done on four sensory nerves (median, ulnar, radial, sural) and two motor nerves (median, peroneal) using standard methodology and department-based normal values 15. Motor unit number estimation (MUNE) was done with a statistical MUNE program, a Nicolet Viking Select machine (Cardinal Health, Dublin, OH), and Shefner modification16 on the abductor pollicis brevis 17. All subjects were evaluated on the right side unless severe atrophy produced very low compound muscle action potentials (CMAPs), in which case the left side was used or the abductor digiti minimi was substituted.…”

Spinal and Bulbar Muscular Atrophy

“…4 The motor unit nerve estimation (MUNE) is reduced to about 50% of healthy control values in the abductor pollicis brevis muscle. 28 Muscle biopsy may show evidence of both myopathic (central nuclei, myofibrillar disorganization) and neurogenic (fiber type grouping, angulated fibers) changes. 29 …”