OC07: Monitoring disease progression with electrophysiological markers derived from compound muscle action potential scans in amyotrophic lateral sclerosis

Abstract

To determine which electrophysiological markers derived from the compound muscle action potential (CMAP) scan are most sensitive to monitor disease progression in patients with amyotrophic lateral sclerosis (ALS), and whether they hold value for clinical trials. Methods: A multicenter collaboration was initiated between MND centers in Denmark, Turkey, Australia and the Netherlands to retrospectively assess longitudinal electrophysiological and ALS functional rating scale (ALSFRS-R) patterns. For each patient we determined the change over time in maximum CMAP (CMAPmax), D50 (number of largest discontinuities within CMAP scans), returners (number of increased CMAPs with decreasing stimulus currents), a motor unit number estimate (MUNE) and MU size properties (e.g. mean, largest unit). Linear mixed models were used to estimate variance components and population averages. Results were translated to required sample sizes for trials. Results: In total, 225 thenar CMAP scans from 65 patients were obtained. The ALSFRS-R decreased on average by 0.9 points/month (95% CI -1.2 to -0.7). MUNE, D50 and CMAPmax showed the largest decrease over time with -0.09, -0.09, and -0.05 standard deviations per month, respectively. In terms of sample size, the ALSFRS-R required 388 patients for a 6-month trial with visits every two months, whereas MUNE required 314 patients (-19.1%) to detect a 30% reduction in progression rate. Conclusion: The electrophysiological markers show considerable variability in their ability to monitor disease progression. MUNE showed to be the most suitable derivate. Further developments and standardization of the CMAP scan could refine its utility for ALS clinical trials.