Changes in Motor Unit Number Estimate and Forced Vital Capacity as Predictors of ALS Progression

Authors

  • Nicholas Olney Providence
  • Catherine Lomen Hoerth
  • Michael Kohn
  • Richard Olney

DOI:

https://doi.org/10.17161/rrnmf.v1i4.13705

Keywords:

ALS, amyotrophic lateral sclerosis, FVC, MUNE, EMG

Abstract

Background: An independent measure of lower motor neuron function that can be monitored over time is essential to evaluating the effect of drugs or stem cell transplantation and to determining prognosis in amyotrophic lateral sclerosis (ALS).  Longitudinal changes in forced vital capacity-percent of predicted (FVC%) and motor unit number estimate (MUNE) may identify patient groups with more rapid disease progression.

Objective: We attempted to define cutoff values for 3-month changes in FVC% and MUNE that identify ALS patients with rapidly progressive disease defined as survival of 30 months or less from symptom onset.

Design: Cohort study.

Subjects: We report data from 26 ALS patients, 10 patients reported previously and 16 patients not reported previously, except for the reproducibility of their MUNE data.

Results: Of the 26 patients, 7 had rapid progression.  Either a 40% decrease in statistical MUNE or a 20% decrease in FVC% over 3 months identified 6 of 7 rapid progressors (Sensitivity=86% 95% confidence interval [CI] 42.1% - 99.6%).  Of the 19 patients without rapid progression, 18 met neither the FVC or MUNE criterion (Specificity = 94.7% CI 95% 74.0% - 99.9%).  In a proportional hazards model, 3 month change in both FVC and MUNE were significantly predictive of decreased survival.

Conclusion: We suggest the use of a three-month change in MUNE or FVC% as a secondary enrollment criterion in therapeutic trials or to identify a subgroup of rapid progressors that may respond differently to treatments.

Downloads

Download data is not yet available.

Author Biography

Richard Olney

Deceased

References

1. Bromberg MB. Updating motor unit number estimation (MUNE). Clin Neurophysiol 2007;118:1-8.
2. Shefner JM, Gooch CL. Motor unit number estimation in neurologic disease. Adv Neurol 2002;88:33-52.
3. McComas AJ, Fawcett PR, Campbell MJ, Sica RE. Electrophysiological estimation of the number of motor units within a human muscle. J Neurol Neurosurg Psychiatry 1971;34:121-131.
4. Kadrie HA, Yates SK, Milner-Brown HS, Brown WF. Multiple point electrical stimulation of ulnar and median nerves. J Neurol Neurosurg Psychiatry 1976;39:973-985.
5. Boe SG, Stashuk DW, Doherty TJ. Motor unit number estimation by decomposition-enhanced spike-triggered averaging: control data, test-retest reliability, and contractile level effects. Muscle Nerve 2004;29:693-699.
6. Boe SG, Stashuk DW, Brown WF, Doherty TJ. Decomposition-based quantitative electromyography: effect of force on motor unit potentials and motor unit number estimates. Muscle Nerve 2005;31:365-373.
7. Daube JR. Estimating the number of motor units in a muscle. J Clin Neurophysiol 1995;12:585-594.
8. Lomen-Hoerth C, Olney RK. Comparison of multiple point and statistical motor unit number estimation. Muscle Nerve 2000;23:1525-1533.
9. Nandedkar SD, Nandedkar DS, Barkhaus PE, Stalberg EV. Motor unit number index (MUNIX). IEEE Trans Biomed Eng 2004;51:2209-2211.
10. Furtula J, Johnsen B, Christensen PB, et al. MUNIX and incremental stimulation MUNE in ALS patients and control subjects. Clin Neurophysiol 2013;124:610-618.
11. Yuen EC, Olney RK. Longitudinal study of fiber density and motor unit number estimate in patients with amyotrophic lateral sclerosis. Neurology 1997;49:573-578.
12. Felice KJ. A longitudinal study comparing thenar motor unit number estimates to other quantitative tests in patients with amyotrophic lateral sclerosis. Muscle Nerve 1997;20:179-185.
13. de Carvalho M, Swash M. Sensitivity of electrophysiological tests for upper and lower motor neuron dysfunction in ALS: a six-month longitudinal study. Muscle & nerve 2010;41:208-211.
14. Aggarwal A, Nicholson G. Detection of preclinical motor neurone loss in SOD1 mutation carriers using motor unit number estimation. J Neurol Neurosurg Psychiatry 2002;73:199-201.
15. Stambler N, Charatan M, Cedarbaum JM. Prognostic indicators of survival in ALS. ALS CNTF Treatment Study Group. Neurology 1998;50:66-72.
16. Vender RL, Mauger D, Walsh S, Alam S, Simmons Z. Respiratory systems abnormalities and clinical milestones for patients with amyotrophic lateral sclerosis with emphasis upon survival. Amyotroph Lateral Scler 2007;8:36-41.
17. Olney RK, Yuen EC, Engstrom JW. Statistical motor unit number estimation: reproducibility and sources of error in patients with amyotrophic lateral sclerosis. Muscle Nerve 2000;23:193-197.
18. Cronin S, Blauw HM, Veldink JH, et al. Analysis of genome-wide copy number variation in Irish and Dutch ALS populations. Hum Mol Genet 2008;17:3392-3398.
19. Cronin S, Greenway MJ, Prehn JH, Hardiman O. Paraoxonase promoter and intronic variants modify risk of sporadic amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2007;78:984-986.
20. Daoud H, Valdmanis PN, Kabashi E, et al. Contribution of TARDBP mutations to sporadic amyotrophic lateral sclerosis. J Med Genet 2009;46:112-114.
21. Dunckley T, Huentelman MJ, Craig DW, et al. Whole-genome analysis of sporadic amyotrophic lateral sclerosis. N Engl J Med 2007;357:775-788.
22. Paubel A, Violette J, Amy M, et al. Mutations of the ANG gene in French patients with sporadic amyotrophic lateral sclerosis. Arch Neurol 2008;65:1333-1336.
23. van Es MA, Van Vught PW, Blauw HM, et al. ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Lancet Neurol 2007;6:869-877.
24. van Es MA, van Vught PW, Blauw HM, et al. Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis. Nat Genet 2008;40:29-31.
25. Chio A, Schymick JC, Restagno G, et al. A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis. Hum Mol Genet 2009;18:1524-1532.

Downloads

Published

2020-09-21

How to Cite

Olney, N., Lomen Hoerth, C., Kohn, M., & Olney, R. (2020). Changes in Motor Unit Number Estimate and Forced Vital Capacity as Predictors of ALS Progression. RRNMF Neuromuscular Journal, 1(4), 6-10. https://doi.org/10.17161/rrnmf.v1i4.13705

Issue

Section

New Discoveries/New Stuff (Original Research)