title: Dysfunction of the neuromuscular junction in spinal muscular atrophy types 2 and 3.
abstract: OBJECTIVE
  Spinal muscular atrophy (SMA) is pathologically characterized by degeneration of anterior horn cells. Recent observations in animal models of SMA and muscle tissue from patients with SMA suggest additional abnormalities in the development and maturation of the neuromuscular junction. We therefore evaluated neuromuscular junction function in SMA with repetitive nerve stimulation.
  
  
  METHODS
  In this case-control study, repetitive nerve stimulation was performed in 35 patients with SMA types 2, 3, and 4, 20 healthy controls, and 5 controls with motor neuron disease.
  
  
  RESULTS
  Pathologic decremental responses (>10%) during 3-Hz repetitive nerve stimulation were observed in 17 of 35 patients (49%) with SMA types 2 and 3, but not in healthy controls or controls with motor neuron disease. None of the patients or controls had an abnormal incremental response of >60%. The presence of an abnormal decremental response was not specific for the type of SMA, nor was it associated with compound muscle action potential amplitude, clinical scores, or disease duration. Two of 4 patients with SMA type 3 who tried pyridostigmine reported increased stamina.
  
  
  CONCLUSIONS
  These data suggest dysfunction of the neuromuscular junction in patients with SMA types 2 and 3. Therefore, drugs that facilitate neuromuscular transmission are candidate drugs for evaluation in carefully designed, placebo-controlled, clinical trials.
authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Renske I
authors.initials: RI
authors.lastname: Wadman
authors.forename: Alexander F J E
authors.initials: AF
authors.lastname: Vrancken
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
authors.forename: W Ludo
authors.initials: WL
authors.lastname: van der Pol
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D002800:Cholinesterase Inhibitors; D004558:Electric Stimulation / Q000379:methods; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000150:complications; D009134:Muscular Atrophy, Spinal / Q000145:classification* / Q000150:complications*; D020511:Neuromuscular Junction Diseases / Q000209:etiology*; D011729:Pyridostigmine Bromide; D014897:Spinal Muscular Atrophies of Childhood / Q000150:complications; D055815:Young Adult
chemical_list: D002800:Cholinesterase Inhibitors; D011729:Pyridostigmine Bromide