Bayesian statistical MUNE method

Abstract

We have developed a new method of motor unit number estimation (MUNE) for assessing diseases such as amyotrophic lateral sclerosis (ALS). We used data from the whole stimulus-response curve and then performed a Bayesian statistical analysis. The Bayesian method uses mathematical equations that express the basic elements of motor unit activation after electrical stimulation and allows for the sources of variability and uncertainty in this formulation. The Bayesian MUNE method was used to determine the most probable number of motor units in 8 normal subjects, 49 ALS subjects, and 3 subjects with progressive lower motor neuron (LMN) weakness. In normals the number of motor units was calculated to be 75-85 in hand and 40-58 in foot muscles. In ALS subjects the number of motor units per muscle was less than in normal subjects. In 17 ALS subjects and 3 subjects with LMN weakness the median, ulnar, or peroneal nerve was studied on repeated occasions over an average of 189 days (range 63-1,071) and the number of motor units progressively declined, with a half-life ranging from 62-834 days. The results of our MUNE technique were reproducible on replicate studies. A Bayesian statistical MUNE method is a new approach that can be used to study ALS patients serially for assessment and treatment trials.

Assessment of Motor Units in Neuromuscular Disease

“…The CMAP scan involves gradual increments in stimulus intensity with the subsequent measurement of the CMAP size [72][73][74][75][76]. It is attractive because it studies all of the motor units in a muscle, and has been shown to measure effectively the decline in motor unit number across a range of different rates of disease progression [74].…”

“…It is attractive because it studies all of the motor units in a muscle, and has been shown to measure effectively the decline in motor unit number across a range of different rates of disease progression [74]. However, at present, applications either require off-line analysis (Bayesian MUNE) [73,74], or have not been validated across the different stages of disease progression [77].…”

Mechanisms, models and biomarkers in amyotrophic lateral sclerosis

“…Using rate of decline as well as variability, hypothetical power analyses suggested that this measure might reduce both sample size and study duration in phase II trials. Other new MUNE methods, including MUNIX (90) and Bayseian MUNE (91,92) are also being developed. While no physiological method of motor unit number estimation has been validated against anatomical motor unit counts, their use as potential endpoints in clinical trials shows great promise.…”

How to Assess Disease’s Severity and Monitor Patients with Amyotrophic Lateral Sclerosis: Lessons from Neurophysiology

“…At least two consecutive MUNE measures are usually performed on each patient to verify the consistency of our results; when required, further estimation was made until the MUNE was clearly stable. The mean of the two or more tests was calculated (Henderson et al, 2007). The results showed an excellent reproducibility with test-retest correlation coefficients ranging from 0.75 to 0.86 (Sartucci et al, 2007).…”