Advancing disease monitoring of amyotrophic lateral sclerosis with the compound muscle action potential scan. Issue 12 (December 2021)

• Record Type: Journal Article
• Authors: Sleutjes, Boudewijn T.H.M.; Bystrup Jacobsen, Anna; Tankisi, Hatice; Gorkem Sirin, N.; Emre Oge, A.; Henderson, Robert D.; van Doorn, Pieter A.; van den Berg, Leonard H.; van Eijk, Ruben P.A.
• Is Part Of: Clinical neurophysiology. Volume 132:Issue 12(2021)
• Page Start: 3152
• Page End: 3159
• Publication Date: 2021-12
• Subjects: Compound muscle action potential scan -- Motor unit number estimation -- Motor unit sizes -- Electrophysiological markers -- Monitoring disease progression -- Clinical trials; A50 smallest size of the motor units making up the N50 -- ALS amyotrophic lateral sclerosis -- ALSFRS-R ALS functional rating scale -- BLUP best linear unbiased prediction -- CMAP compound muscle action potential -- D50 number of largest discontinuities required to elicit 50% of maximum CMAP -- FMF fine motor function -- LME linear mixed effects -- MND motor neuron disease -- MU motor unit -- MUNE motor unit number estimation -- N50 number of largest MUs required to elicit 50% of the maximum CMAP -- PMA progressive muscular atrophy -- PLS primary lateral sclerosis -- RR relative range -- S5 stimulus current required to elicit a target CMAP of 5% of the maximum CMAP -- S50 stimulus current required to elicit a target CMAP of 50% of the maximum CMAP -- S95 stimulus current required to elicit a target CMAP of 95% of the maximum CMAP; Neurophysiology -- Periodicals; Electroencephalography -- Periodicals; Electromyography -- Periodicals; Neurology -- Periodicals; 612.8
• DOI: 10.1016/j.clinph.2021.09.014
• Languages: English
• ISSNs: 1388-2457

Abstract

Highlights: Compound muscle action potential scan-derived markers are sensitive to track disease progression in amyotrophic lateral sclerosis. Motor unit number estimation was most sensitive and may increase efficiency of clinical trials compared to clinical endpoints. Standardization of compound muscle action potential scans can further maximize its utility for clinical use and research. Abstract: Objective: To determine which compound muscle action potential (CMAP) scan-derived electrophysiological markers are most sensitive for monitoring disease progression in amyotrophic lateral sclerosis (ALS), and whether they hold value for clinical trials. Methods: We used four independent patient cohorts to assess longitudinal patterns of a comprehensive set of electrophysiological markers including their association with the ALS functional rating scale (ALSFRS-R). Results were translated to trial sample size requirements. Results: In 65 patients, 225 thenar CMAP scan recordings were obtained. Electrophysiological markers showed extensive variation in their longitudinal trajectories. Expressed as standard deviations per month, motor unit number estimation (MUNE) values declined by 0.09 (CI 0.07–0.12), D50, a measure that quantifies CMAP scan discontinuities, declined by 0.09 (CI 0.06–0.13) and maximum CMAP by 0.05 (CI 0.03–0.08). ALSFRS-R declined fastest (0.12, CI 0.08 – 0.15), however the between-patient variability was larger compared to electrophysiological markers, resulting in larger sample sizes. MUNE reduced the sample size by 19.1% (n = 388 vs n = 314) for a 6-month study compared to the ALSFRS-R. Conclusions: CMAP scan-derived markers show promise in monitoring disease progression in ALS patients, where MUNE may be its most suitable derivate. Significance: MUNE may increase clinical trial efficiency compared to clinical endpoints.