title: Younger children with MS have a distinct CSF inflammatory profile at disease onset.
abstract: BACKGROUND
  The clinical and MRI presentation differs between earlier- and later-onset pediatric multiple sclerosis (MS), whereas the effect of age on the CSF inflammatory profile is unknown and may contribute to delayed diagnosis.
  
  
  OBJECTIVE
  To compare the CSF cellular and immunoglobulin G (IgG) profiles between earlier- and later-onset pediatric MS.
  
  
  METHODS
  We queried the databases of 6 pediatric MS centers for earlier-onset (onset <11 years) and later-onset (> or = 11 and <18 years) patients with MS or clinically isolated syndrome who underwent CSF analysis within the first 3 months of presentation (observational study). We compared CSF white blood cell (WBC) differential count, IgG index, and IgG oligoclonal bands between age groups.
  
  
  RESULTS
  We identified 40 earlier-onset (mean age at onset = 7.2 +/- 2.7 years, 60% females) and 67 later-onset pediatric MS patients (15.1 +/- 1.7 years, 63% females). Although WBC count tended to be higher in earlier-onset patients (median = 9/mm(3) [0-343] vs 6 [0-140], p = 0.15), they had a lower proportion of lymphocytes (70% [0-100] vs 93% [0-100] of WBCs, p = 0.0085; difference = +3% per 1-year increase of age, p = 0.0011) and higher proportion of neutrophils than later-onset patients (0.5% [0-75] vs 0% [0-50] of WBCs, p = 0.16; difference = -1% per 1-year increase of age, p = 0.033). In earlier-onset disease, fewer patients had an elevated IgG index than in the later-onset group (35% vs 68% of patients, p = 0.031).
  
  
  CONCLUSIONS
  Age modifies the CSF profile at pediatric multiple sclerosis (MS) onset, which may mislead the diagnosis. Our findings suggest an activation of the innate rather than the adaptive immune system in the earlier stages of MS or an immature immune response.
authors.affiliation: UCSF Regional Pediatric MS Center, 350 Parnassus Ave., Suite 908, San Francisco, CA 94117, USA. dchabas@gmail.com
authors.forename: D
authors.initials: D
authors.lastname: Chabas
authors.forename: J
authors.initials: J
authors.lastname: Ness
authors.forename: A
authors.initials: A
authors.lastname: Belman
authors.forename: E A
authors.initials: EA
authors.lastname: Yeh
authors.forename: N
authors.initials: N
authors.lastname: Kuntz
authors.forename: M P
authors.initials: MP
authors.lastname: Gorman
authors.forename: J B
authors.initials: JB
authors.lastname: Strober
authors.forename: I
authors.initials: I
authors.lastname: De Kouchkovsky
authors.forename: C
authors.initials: C
authors.lastname: McCulloch
authors.forename: T
authors.initials: T
authors.lastname: Chitnis
authors.forename: M
authors.initials: M
authors.lastname: Rodriguez
authors.forename: B
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.forename: L B
authors.initials: LB
authors.lastname: Krupp
authors.forename: E
authors.initials: E
authors.lastname: Waubant
mesh_terms: D000293:Adolescent; D000367:Age Factors; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid*; D007958:Leukocyte Count / Q000379:methods; D008137:Longitudinal Studies; D008297:Male; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000276:immunology*; D010372:Pediatrics; D016016:Proportional Hazards Models; D012720:Severity of Illness Index
chemical_list: D007074:Immunoglobulin G