TY - JOUR
T1 - Advancing disease monitoring of amyotrophic lateral sclerosis with the compound muscle action potential scan
AU - Sleutjes, Boudewijn T.H.M.
AU - Bystrup Jacobsen, Anna
AU - Tankisi, Hatice
AU - Gorkem Sirin, N.
AU - Emre Oge, A.
AU - Henderson, Robert D.
AU - van Doorn, Pieter A.
AU - van den Berg, Leonard H.
AU - van Eijk, Ruben P.A.
N1 - Publisher Copyright:
© 2021 International Federation of Clinical Neurophysiology
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Clinical trials
KW - Compound muscle action potential scan
KW - Electrophysiological markers
KW - Monitoring disease progression
KW - Motor unit number estimation
KW - Motor unit sizes
UR - http://www.scopus.com/inward/record.url?scp=85118567554&partnerID=8YFLogxK
U2 - 10.1016/j.clinph.2021.09.014
DO - 10.1016/j.clinph.2021.09.014
M3 - Journal article
C2 - 34749234
AN - SCOPUS:85118567554
SN - 1388-2457
VL - 132
SP - 3152
EP - 3159
JO - Clinical Neurophysiology
JF - Clinical Neurophysiology
IS - 12
ER -