Changes in Motor Unit Number Estimate and Forced Vital Capacity as Predictors of ALS Progression

Background: An independent measure of lower motor neuron function that can be monitored over time is essential to evaluating the effect of drugs or stem cell transplantation and to determining prognosis in amyotrophic lateral sclerosis (ALS).  Longitudinal changes in forced vital capacity-percent of predicted (FVC%) and motor unit number estimate (MUNE) may identify patient groups with more rapid disease progression. Objective: We attempted to define cutoff values for 3-month changes in FVC% and MUNE that identify ALS patients with rapidly progressive disease defined as survival of 30 months or less from symptom onset. Design: Cohort study. Subjects: We report data from 26 ALS patients, 10 patients reported previously and 16 patients not reported previously, except for the reproducibility of their MUNE data. Results: Of the 26 patients, 7 had rapid progression.  Either a 40% decrease in statistical MUNE or a 20% decrease in FVC% over 3 months identified 6 of 7 rapid progressors (Sensitivity=86% 95% confidence interval [CI] 42.1% - 99.6%).  Of the 19 patients without rapid progression, 18 met neither the FVC or MUNE criterion (Specificity = 94.7% CI 95% 74.0% - 99.9%).  In a proportional hazards model, 3 month change in both FVC and MUNE were significantly predictive of decreased survival. Conclusion: We suggest the use of a three-month change in MUNE or FVC% as a secondary enrollment criterion in therapeutic trials or to identify a subgroup of rapid progressors that may respond differently to treatments.