title: Motor Unit Number Index (MUNIX) detects motor neuron loss in pre-symptomatic muscles in Amyotrophic Lateral Sclerosis.
abstract: OBJECTIVE
  Motor Unit Number Index (MUNIX) is a quantitative neurophysiological measure that provides an index of the number of lower motor neurons supplying a muscle. It reflects the loss of motor neurons in patients with Amyotrophic Lateral Sclerosis (ALS). However, it is unclear whether MUNIX also detects motor unit loss in strong, non-wasted muscles.
  
  
  METHODS
  Three centres measured MUNIX in 49 ALS patients every three months in six different muscles (abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, extensor digitorum brevis, abductor hallucis) on the less affected side. The decline of MUNIX in initially non-wasted, clinically strong muscles (manual muscle testing, MMT grade 5) was analysed before and after onset of weakness.
  
  
  RESULTS
  In 49 subjects, 151 clinically strong muscles developed weakness and were included for analysis. The average monthly relative loss of MUNIX was 5.0% before and 5.6% after onset of weakness. This rate of change was significantly higher compared to ALS functional rating scale (ALSFRS-R) and compound muscle action potential (CMAP) change over 12months prior to the onset of muscle weakness (p=0.024).
  
  
  CONCLUSIONS
  MUNIX is an electrophysiological marker that detects lower motor neuron loss in ALS, before clinical weakness becomes apparent by manual muscle testing.
  
  
  CONCLUSIONS
  This makes MUNIX a good biomarker candidate for disease progression and possibly pharmacodynamics responds.
authors.affiliation: Neuromuscular Diseases Unit/ALS Clinic, Kantonsspital St. Gallen, St. Gallen, Switzerland. Electronic address: christoph.neuwirth@kssg.ch.
authors.forename: Christoph
authors.initials: C
authors.lastname: Neuwirth
authors.affiliation: Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Barkhaus
authors.affiliation: Neuromuscular Diseases Unit/ALS Clinic, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Burkhardt
authors.affiliation: Department of Neurosciences, Hospital de Santa Maria, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Castro
authors.affiliation: Kantonsspital Winterthur, Winterthur, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Czell
authors.affiliation: Department of Neurosciences, Hospital de Santa Maria, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: Mamede
authors.initials: M
authors.lastname: de Carvalho
authors.affiliation: Natus Medical Inc, Middleton, WI, USA.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Nandedkar
authors.affiliation: Institute of Neurosciences, Uppsala University, Department of Clinical Neurophysiology, University Hospital, Uppsala, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Stålberg
authors.affiliation: Neuromuscular Diseases Unit/ALS Clinic, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Neurology, University Hospital Basel, Basel, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Weber
mesh_terms: D000368:Aged; D000465:Algorithms; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis*; D004576:Electromyography / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000473:pathology* / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation / Q000503:physiopathology*
keywords: ALSFRS-R; Biomarker; MUNIX; Multicentre; Pre-symptomatic ALS