title: Progressive axonal dysfunction and clinical impairment in amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  To elucidate longitudinal changes in axonal function in amyotrophic lateral sclerosis (ALS) patients, and to relate such changes with motor unit loss and functional impairment.
  
  
  METHODS
  37 ALS patients (age, 53.7 ± 1.7 years; 22 males) were studied using axonal excitability techniques at baseline and 12 weeks follow-up.
  
  
  RESULTS
  Longitudinal measurements across excitability parameters suggested increasing K(+) channel dysfunction, with further increases in depolarising threshold electrotonus (90-100 ms, baseline, 46.8 ± 1.0%; follow-up, 48.7 ± 0.8%; P=0.02) and superexcitability (baseline, -24.0 ± 1.2%; 12 weeks, -26.0 ± 1.2%; P=0.04). Patients with preserved compound muscle action potential (CMAP) amplitude at follow-up developed more severe changes in axonal excitability than those in whom CMAP decreased from baseline, suggesting that the most pronounced disease effects were on motor axons immediately prior to axonal loss in ALS patients. Fine motor decline was associated with more severe changes in axonal excitability, suggesting that functional impairment was related to axonal dysfunction.
  
  
  CONCLUSIONS
  Longitudinal changes in axonal excitability in ALS patients suggest increasing K(+) channel dysfunction in motor axons.
  
  
  CONCLUSIONS
  Axonal excitability studies enable investigation of longitudinal changes in axonal ion channel dysfunction, and thereby the processes that potentially contribute to axonal degeneration in ALS.
authors.affiliation: Neuroscience Research Australia, Sydney, New South Wales, Australia. M.Kiernan@unsw.edu.au
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Cheah
authors.forename: Cindy S Y
authors.initials: CS
authors.lastname: Lin
authors.forename: Susanna B
authors.initials: SB
authors.lastname: Park
authors.forename: Steve
authors.initials: S
authors.lastname: Vucic
authors.forename: Arun V
authors.initials: AV
authors.lastname: Krishnan
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Kiernan
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology*; D001369:Axons / Q000502:physiology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000502:physiology; D009410:Nerve Degeneration / Q000503:physiopathology; D015221:Potassium Channels / Q000502:physiology
chemical_list: D015221:Potassium Channels