@article{8e0670538e5c447ca967d94b964d7af6,
title = "Multipoint incremental motor unit number estimation as an outcome measure in ALS",
abstract = "Background: Improved outcome measures are necessary to reduce sample size and increase power in amyotrophic lateral sclerosis (ALS) clinical trials. Motor unit number estimation (MUNE) is a potentially attractive tool. MUNE methods previously employed in multicenter trials exhibited excessive variability and were prone to artifact. Objective: To evaluate a modification of standard incremental MUNE in a multicenter natural history study of subjects with ALS. Methods: Fifty healthy subjects were evaluated twice and 71 subjects with ALS were studied repeatedly for up to 500 days. Side and nerve studied was based on clinical examination findings. Nerves were stimulated at 3 specified locations and 3 increments were obtained at each location. Average single motor unit action potential (SMUP) amplitude was calculated by adding the amplitude of the third increment at each location and dividing by 9; SMUP was divided into maximum CMAP amplitude to determine the MUNE. Results: Test-retest variability was 9% in normal subjects. Average MUNE for normal subjects was 225 (±87), and was 41.9 (±39) among subjects with ALS at baseline. Subjects with ALS showed clear decrements over time, with an overage rate of decline of approximately 9% per month. SMUP amplitude increased with time in a fashion consistent with the known pathophysiology of ALS. Conclusion: Multipoint incremental MUNE has a number of attributes that make it attractive as an outcome measure in ALS and other diseases characterized by motor unit loss. It can be rapidly performed on any EMG machine and has repeatability and rates of decline that favorably compare to other previously described methods.",
author = "Shefner, {J. M.} and Watson, {M. L.} and L. Simionescu and Caress, {J. B.} and Burns, {T. M.} and Maragakis, {N. J.} and M. Benatar and David, {W. S.} and Sharma, {K. R.} and Rutkove, {S. B.}",
note = "Funding Information: Dr. Shefner serves on a DSMB for the NIH; serves as Neuromuscular Section Editor for and receives publishing royalties from UpToDate ; has served as a consultant for Teva Pharmaceutical Industries Ltd., Gilead Sciences, Inc., GlaxoSmithKline, Trophos, and BrainGate; and receives research support from Isis Pharmaceuticals, Inc., Neuralstem, Inc., GlaxoSmithKline, sanofi-aventis, Teva Pharmaceutical Industries Ltd., Knopp Neurosciences Inc., Cytokinetics Inc., the NIH, and the ALS Association. M.L. Watson reports no disclosures. Dr. Simionescu receives research support from the NIH/NINDS. Dr. Caress has served as a consultant for ALS Biopharma, LLC and has received research support from GlaxoSmithKline, Talecris Biotherapeutics, the NIH/NINDS, and the ALS Association. Dr. Burns serves as Podcast Section Editor for Neurology {\textregistered}; has served as a consultant for Bayhill Therapeutics; and has received research support from Knopp Neurosciences Inc. and the Myasthenia Gravis Foundation of America. Dr. Maragakis serves on a scientific advisory board for Q Therapeutics, Inc.; received support from the Michael S. Ansari Gift Fund for basic science research; serves as a contributor to UpToDate ; has served as a consultant for California Institute for Regenerative Medicine (CIRM); and receives/has received research support from Cytokinetics Inc., Sangamo BioSciences, Inc., TEDCO-Maryland Stem Cell Research Fund, NIH/NINDS, U.S. Department of Defense, and the ALS Association Packard Center for ALS Research at Johns Hopkins. Dr. Benatar has served as a consultant for Bayhill Therapeutics and Cytokinetics Inc.; receives publishing royalties for Neuromuscular Disease: Evidence and Analysis in Clinical Neurology (Humana Press, 2006) , BluePrints in Neurology , (Lippincott Williams & Wilkins, 2002), and Field of Vision: A Manual and Atlas of Perimetry (Humana Press, 2010); receives/has received research support from CytRx Corporation, the Muscular Dystrophy Association, the ALS Association, the Food & Drug Administration, and the Centers for Disease Control and Prevention, the Woodruff Health Sciences Center (Emory University), and the NIH; and has participated in medico-legal cases. Dr. David has served as a consultant for Apnex Medical{\texttrademark}, Inc. and Allergan, Inc. Dr. Sharma reports no disclosures. Dr. Rutkove has 2 patents pending re: Electrical impedance myography; receives royalties from UpToDate, Inc . and for the publication of The Clinical Neurophysiology Primer (Humana Press, 2007); serves as a consultant for and holds stock in Convergence Medical Devices, Inc.; serves as a consultant to Neuralstem, Inc.; and receives research support from the NIH/NINDS, the SMA Foundation, and the ALS Association.",
year = "2011",
month = jul,
day = "19",
doi = "10.1212/WNL.0b013e318225aabf",
language = "English (US)",
volume = "77",
pages = "235--241",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "3",
}