Motor Unit Number Estimation for Evaluating Disease Progression and Comparison With Functional Rating Scale Scores in...

Introduction Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease characterized by degeneration of motor neurons in the brain, brainstem, and spinal cord. While the ALS Functional Rating Scale-Revised (ALSFRS-R) is commonly used to assess functional decline, its limitations highlight the need for more objective biomarkers. Motor unit number estimation (MUNE) is an electrophysiological technique that may provide a more sensitive measure of disease progression. This study aims to evaluate the utility of MUNE as a biomarker in ALS and compare its performance with ALSFRS-R. Methods This was a prospective, single-center, observational study conducted over 18 months. A total of 31 patients with definite or probable ALS, diagnosed per the Revised El Escorial Criteria, were enrolled. MUNE and ALSFRS-R assessments were performed at baseline and after six months. MUNE was calculated using the multi-point incremental method in the upper extremity. Data were analyzed using paired t-tests and Pearson's correlation coefficients. Subgroup analyses by age, sex, and symptom onset site were also conducted.  Results Both MUNE and ALSFRS-R scores declined significantly over six months. The mean MUNE decreased from 16.36 ± 5.22 to 13.37 ± 4.96 (p < 0.0001), while the ALSFRS-R score declined from 42.06 ± 3.24 to 36.72 ± 4.89 (p < 0.0001). The mean rate of decline was significantly greater for MUNE (23.6 ± 15.31) than for ALSFRS-R (13.91 ± 8.18; p = 0.001). No significant associations were observed between MUNE and patient age, sex, or site of symptom onset. Correlation between MUNE and ALSFRS-R was weak at both time points. Conclusions MUNE demonstrated a significantly greater rate of decline than ALSFRS-R, suggesting higher sensitivity to motor neuron loss over time. These findings support using MUNE as a reliable and objective biomarker for monitoring disease progression in ALS. Incorporating MUNE into clinical practice and research may improve prognostication, enable earlier therapeutic intervention, and enhance patient stratification in clinical trials. Further large-scale studies are needed to validate its routine use.