title: Prognostic significance of neurologic examination findings in Wilson disease.
abstract: BACKGROUND
  Wilson disease patients present with any of several neurologic phenotypes, and their treated outcomes vary widely. Our goal was to determine whether presenting clinical features of neurologic Wilson disease (WD) predict longer term neurologic outcomes in patients receiving anticopper treatment.
  
  
  METHODS
  Patients enrolled in four WD treatment trials received a standardized neurologic examination at trial enrollment and then at pre-specified intervals following anticopper therapy, initially with tetrathiomolybdate or trientine and then with zinc. The examination scored patients' motor signs, including tremor, rigidity, dystonia, dyarthria, and gait. The Total Score was obtained by summing these subscores. Eighty-six patients were included in our analysis, with a mean follow-up of 34.7 months. Retrospectively, the analysis compared scaled and unscaled sign subscores at enrollment and follow-up with change in the Total Score, using a generalized estimating equations approach.
  
  
  RESULTS
  In the primary analysis, improvement in the Total Score was best predicted by sign subscores for tremor (beta -0.7, p = 0.006), gait abnormalities (beta -3.7, p < 0.001), and speech (beta = -1.3, p = 0.05). Dystonia (beta = 1.8, p < 0.001) and facial expression (beta = 1.9, p = 0.03) were associated with worsening Total Score. Of the motor signs followed individually, dystonia proved most resistant to treatment.
  
  
  CONCLUSIONS
  This is the first large-scale prospectively acquired study assessing prognostic significance of specific neurologic signs in WD. Our data support the historical observations that tremor is a favorable prognostic sign while dystonia is relatively refractory to treatment in WD.
authors.affiliation: Department of Neurology, University of Michigan, 1150 W Medical Center Dr., Ann Arbor, MI 48109-5604, USA. jamesbur@med.umich.edu
authors.forename: James F
authors.initials: JF
authors.lastname: Burke
authors.forename: Praveen
authors.initials: P
authors.lastname: Dayalu
authors.forename: Bin
authors.initials: B
authors.lastname: Nan
authors.forename: Fred
authors.initials: F
authors.lastname: Askari
authors.forename: George J
authors.initials: GJ
authors.lastname: Brewer
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Lorincz
mesh_terms: D000328:Adult; D002614:Chelating Agents / Q000627:therapeutic use; D004421:Dystonia / Q000209:etiology; D005260:Female; D006527:Hepatolenticular Degeneration / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy; D006801:Humans; D008297:Male; D008982:Molybdenum / Q000627:therapeutic use; D009460:Neurologic Examination; D011379:Prognosis; D012307:Risk Factors; D014202:Tremor / Q000209:etiology; D014266:Trientine / Q000627:therapeutic use; D015032:Zinc / Q000627:therapeutic use
chemical_list: D002614:Chelating Agents; D008982:Molybdenum; C020809:tetrathiomolybdate; D015032:Zinc; D014266:Trientine