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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA. shefnerj@upstate.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Shefner
authors.forename: M L
authors.initials: ML
authors.lastname: Watson
authors.forename: L
authors.initials: L
authors.lastname: Simionescu
authors.forename: J B
authors.initials: JB
authors.lastname: Caress
authors.forename: T M
authors.initials: TM
authors.lastname: Burns
authors.forename: N J
authors.initials: NJ
authors.lastname: Maragakis
authors.forename: M
authors.initials: M
authors.lastname: Benatar
authors.forename: W S
authors.initials: WS
authors.lastname: David
authors.forename: K R
authors.initials: KR
authors.lastname: Sharma
authors.forename: S B
authors.initials: SB
authors.lastname: Rutkove
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000503:physiopathology*; D004185:Disability Evaluation; D004558:Electric Stimulation; D004576:Electromyography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000502:physiology*; D017063:Outcome Assessment, Health Care / Q000379:methods*; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013997:Time Factors; D055815:Young Adult