1. Advancing disease monitoring of amyotrophic lateral sclerosis with the compound muscle action potential scan
- Author
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Hatice Tankisi, Pieter A. van Doorn, Robert D. Henderson, Leonard H. van den Berg, Ruben P A van Eijk, Boudewijn T.H.M. Sleutjes, A. Emre Öge, A.B. Jacobsen, N. Gorkem Sirin, and Neurology
- Subjects
Adult ,Male ,medicine.medical_specialty ,Action Potentials ,Motor unit sizes ,Clinical trials ,Rating scale ,Physiology (medical) ,Internal medicine ,Clinical endpoint ,medicine ,Humans ,Motor unit number estimation ,Amyotrophic lateral sclerosis ,Muscle, Skeletal ,Aged ,Clinical Trials as Topic ,Electromyography ,business.industry ,Amyotrophic Lateral Sclerosis ,Middle Aged ,Compound muscle action potential scan ,medicine.disease ,Sensory Systems ,Compound muscle action potential ,Clinical trial ,Neurology ,Sample size determination ,Electrophysiological markers ,Cardiology ,Female ,Neurology (clinical) ,Monitoring disease progression ,business - 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.
- Published
- 2021