Advancing disease monitoring of amyotrophic lateral sclerosis with the compound muscle action potential scan
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
(2021) Clinical Neurophysiology, volume 132, issue 12, pp. 3152 - 3159
(Article)
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
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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.
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Keywords: Clinical trials, Compound muscle action potential scan, Electrophysiological markers, Monitoring disease progression, Motor unit number estimation, Motor unit sizes, Clinical Neurology, Neurology, Sensory Systems, Physiology (medical), Journal Article
ISSN: 1388-2457
Publisher: Elsevier Ireland Ltd
Note: Funding Information: This study was supported by the Prinses Beatrix Spierfonds (Grant No WAR09-01), the Netherlands ALS foundation (Stichting ALS Nederland), Lundbeck Foundation, Knud and Edith Eriksens Mindefond, Søster and Verner Lipperts Fond, Fonden til Lægevidenskabens Fremme and Aage and Johanne Louis Hansens Fond. Publisher Copyright: © 2021 International Federation of Clinical Neurophysiology
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