Implementing Motor Unit Number Index (MUNIX) in a large clinical trial: Real world experience from 27 centres

Christoph Neuwirth; Nathalie Braun; Kristl G Claeys; Robert Bucelli; Christina Fournier; Mark Bromberg; Susanne Petri; Stephan Goedee; Timothée Lenglet; Ron Leppanen; Antonio Canosa; Ira Goodman; Muhammad Al-Lozi; Takuya Ohkubo; Annemarie Hübers; Nazem Atassi; Agessandro Abrahao; Andreas Funke; Martin Appelfeller; Anke Tümmler; Eoin Finegan; Jonathan D Glass; Suma Babu; Shafeeq S Ladha; Olga Kwast-Rabben; Raul Juntas-Morales; Amina Coffey; Vinay Chaudhry; Tuan Vu; Chow Saephanh; Colleen Newhard; Marion Zakrzewski; Esther Rosier; Nancy Hamel; Divisha Raheja; Jesper Raaijman; Toby Ferguson; Markus Weber

doi:10.1016/j.clinph.2018.04.614

Implementing Motor Unit Number Index (MUNIX) in a large clinical trial: Real world experience from 27 centres

Clin Neurophysiol. 2018 Aug;129(8):1756-1762. doi: 10.1016/j.clinph.2018.04.614. Epub 2018 May 3.

Authors

Christoph Neuwirth¹, Nathalie Braun², Kristl G Claeys³, Robert Bucelli⁴, Christina Fournier⁵, Mark Bromberg⁶, Susanne Petri⁷, Stephan Goedee⁸, Timothée Lenglet⁹, Ron Leppanen¹⁰, Antonio Canosa¹¹, Ira Goodman¹², Muhammad Al-Lozi⁴, Takuya Ohkubo¹³, Annemarie Hübers¹⁴, Nazem Atassi¹⁵, Agessandro Abrahao¹⁶, Andreas Funke¹⁷, Martin Appelfeller¹⁸, Anke Tümmler¹⁸, Eoin Finegan¹⁹, Jonathan D Glass⁵, Suma Babu¹⁵, Shafeeq S Ladha²⁰, Olga Kwast-Rabben²¹, Raul Juntas-Morales²², Amina Coffey¹⁹, Vinay Chaudhry²³, Tuan Vu²⁴, Chow Saephanh²⁵, Colleen Newhard²⁶, Marion Zakrzewski²⁶, Esther Rosier²⁷, Nancy Hamel²⁷, Divisha Raheja²⁸, Jesper Raaijman⁸, Toby Ferguson²⁹, Markus Weber³⁰

Affiliations

¹ Neuromuscular Diseases Unit/ALS Clinic, Kantonsspital St. Gallen, St. Gallen, Switzerland. Electronic address: [email protected].
² Neuromuscular Diseases Unit/ALS Clinic, Kantonsspital St. Gallen, St. Gallen, Switzerland.
³ Department of Neurology, Neuromuscular Reference Centre, University Hospitals Leuven, Leuven, Belgium; Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, Experimental Neurology, KU Leuven, Leuven, Belgium.
⁴ Washington University School of Medicine, Department of Neurology, Washington, USA.
⁵ Emory University, Department of Neurology, Atlanta, USA.
⁶ Clinical Neurosciences Center, Salt Lake City, USA.
⁷ Department of Neurology, Hannover Medical School, Hannover, Germany.
⁸ Brain Centre Rudolf Magnus, Department of Neurology and Neurosurgery, UMC Utrecht, Utrecht, The Netherlands.
⁹ Département de Neurophysiologie, Groupe hospitalier Pitié-Salpêtrière, APHP, Paris, France.
¹⁰ University Neurology and Cole Neuroscience Center, University of Tennessee, Knoxville, USA.
¹¹ ALS Center of Torino, Department of Neuroscience "Rita Levi Montalcini", University of Torino, Torino, Italy.
¹² BioClinica Research Orlando, USA.
¹³ ALS Clinical and Translational Research, University of California, San Diego, USA.
¹⁴ Department of Neurology, University of Ulm, Ulm, Germany.
¹⁵ Neurological Clinical Research Institute (NCRI), Department of Neurology, Massachusetts General Hospital, Boston, USA.
¹⁶ Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
¹⁷ Charité - Universitätsmedizin Berlin, Outpatient Center for ALS and Other Motor Neuron Disorders, Berlin, Germany.
¹⁸ Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
¹⁹ Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.
²⁰ Department of Neurology, Barrow Neurological Institute, Phoenix, USA.
²¹ Department of Pharmacology and Clinical Neuroscience, Umeå, Sweden.
²² Département de Neurologie, CHU de Montpellier, Montpellier, France.
²³ Johns Hopkins University School of Medicine, Baltimore, USA.
²⁴ Neuromuscular Division, University of South Florida, Tampa, USA.
²⁵ California Pacific Medical Center Research Institute, San Francisco, USA.
²⁶ East Campus Health Center, Neurophysiology Department, Hershey, USA.
²⁷ Montreal Neurological Institute and Hospital, Montreal, Canada.
²⁸ Penn State Medical Center Neuroscience Institute, Morgantown, USA.
²⁹ Biogen, USA.
³⁰ Neuromuscular Diseases Unit/ALS Clinic, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Neurology, University Hospital Basel, Basel, Switzerland.

PMID: 29803404
DOI: 10.1016/j.clinph.2018.04.614

Abstract

Objective: Motor Unit Number Index (MUNIX) is a quantitative neurophysiological method that reflects loss of motor neurons in Amyotrophic Lateral Sclerosis (ALS) in longitudinal studies. It has been utilized in one natural history ALS study and one drug trial (Biogen USA) after training and qualification of raters.

Methods: Prior to testing patients, evaluators had to submit test-retest data of 4 healthy volunteers. Twenty-seven centres with 36 raters measured MUNIX in 4 sets of 6 different muscles twice. Coefficient of variation of all measurements had to be <20% to pass the qualification process. MUNIX COV of the first attempt, number of repeated measurements and muscle specific COV were evaluated.

Results: COV varied considerably between raters. Mean COV of all raters at the first measurements was 12.9% ± 13.5 (median 8.7%). Need of repetitions ranged from 0 to 43 (mean 10.7 ± 9.1, median 8). Biceps and first dorsal interosseus muscles showed highest repetition rates. MUNIX variability correlated considerably with variability of compound muscle action potential.

Conclusion: MUNIX revealed generally good reliability, but was rater dependent and ongoing support for raters was needed.

Significance: MUNIX can be implemented in large clinical trials as an outcome measure after training and a qualification process.

Keywords: Implementation; MUNIX; Multicentre; Training; Variability.

Publication types

Multicenter Study
Pragmatic Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Amyotrophic Lateral Sclerosis / diagnosis*
Amyotrophic Lateral Sclerosis / epidemiology
Amyotrophic Lateral Sclerosis / physiopathology*
Female
Humans
Longitudinal Studies
Male
Recruitment, Neurophysiological / physiology*