title: MRI parameters for prediction of multiple sclerosis diagnosis in children with acute CNS demyelination: a prospective national cohort study.
abstract: BACKGROUND
  Multiple sclerosis (MS) diagnostic criteria incorporate MRI features that can be used to predict later diagnosis of MS in adults with acute CNS demyelination. To identify MRI predictors of a subsequent MS diagnosis in a paediatric population, we created a standardised scoring method and applied it to MRI scans from a national prospective incidence cohort of children with CNS demyelination.
  
  
  METHODS
  Clinical and MRI examinations were done at the onset of acute CNS demyelination and every 3 months in the first year after that, and at the time of a second demyelinating attack. MS was diagnosed on the basis of clinical or MRI evidence of relapsing disease. Baseline MRI scans were assessed for the presence of 14 binary response parameters. Parameters were assessed with a multiple tetrachoric correlation matrix. Univariate analyses and multivariable Cox proportional hazards models were used to identify predictors of MS.
  
  
  RESULTS
  Between Sept 1, 2004, and June 30, 2010, 332 children and adolescents were assessed for eligibility. 1139 scans were available from 284 eligible participants who had been followed up for 3·9 (SD 1·7) years. 57 (20%) were diagnosed with MS after a median of 188 (IQR 144-337) days. Seven of 14 binary response parameters were retained. The presence of either one or more T1-weighted hypointense lesions (hazard ratio 20·6, 95% CI 5·46-78·0) or one or more periventricular lesions (3·34, 1·27-8·83) was associated with an increased likelihood of MS diagnosis (sensitivity 84%, specificity 93%, positive predictive value 76%, negative predictive value 96%). Risk for MS diagnosis was highest when both parameters were present (34·27, 16·69-70·38). Although the presence of contrast enhancement, cerebral white matter, intracallosal, and brainstem lesions was associated with MS in the univariate analyses, these parameters were not retained in the multivariable models.
  
  
  CONCLUSIONS
  Specific MRI parameters can be used to predict diagnosis of MS in children with incident demyelination of the CNS. The ability to promptly identify children with MS will enhance timely access to care and will be important for future clinical trials in paediatric MS.
  
  
  BACKGROUND
  Canadian Multiple Sclerosis Scientific Research Foundation.
authors: Neurosciences and Mental Health, Research Institute, The Hospital for Sick Children, University of Toronto, ON, Canada.
authors: Leonard H
authors: LH
authors: Verhey
authors: Helen M
authors: HM
authors: Branson
authors: Manohar M
authors: MM
authors: Shroff
authors: David Ja
authors: DJ
authors: Callen
authors: John G
authors: JG
authors: Sled
authors: Sridar
authors: S
authors: Narayanan
authors: A Dessa
authors: AD
authors: Sadovnick
authors: Amit
authors: A
authors: Bar-Or
authors: Douglas L
authors: DL
authors: Arnold
authors: Ruth Ann
authors: RA
authors: Marrie
authors: Brenda
authors: B
authors: Banwell
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D001921:Brain / Q000473:pathology*; D002648:Child; D003711:Demyelinating Diseases / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies