title: Extensive acute axonal damage in pediatric multiple sclerosis lesions.
abstract: OBJECTIVE
  Axonal damage occurs early in multiple sclerosis (MS) and contributes to the degree of clinical disability. Children with MS more often show disabling and polyfocal neurological symptoms at disease onset than adults with MS. Thus, axonal damage may differ between pediatric and adult MS patients.
  
  
  METHODS
  We analyzed axonal pathology in archival brain biopsy and autopsy samples from 19 children with early MS. Lesions were classified according to demyelinating activity and presence of remyelination. Axonal density and extent of acute axonal damage were assessed using Bielschowsky silver impregnation and immunohistochemistry for amyloid precursor protein (APP), respectively. Axonal injury was correlated with the inflammatory infiltrate as well as clinical characteristics. Results were compared with data from adult MS patients.
  
  
  RESULTS
  Acute axonal damage was most extensive in early active demyelinating (EA) lesions of pediatric patients and correlated positively with the Expanded Disability Status Scale at attack leading to biopsy/autopsy. Comparison with 12 adult patients showed a 50% increase in the extent of acute axonal damage in EA lesions from children compared to adults, with the highest number of APP-positive spheroids found prior to puberty. The extent of acute axonal damage correlated positively with the number of lesional macrophages. Axonal density was reduced in pediatric lesions irrespective of the demyelinating activity or the presence of remyelination. Axonal reduction was similar between children and adults.
  
  
  CONCLUSIONS
  Our results provide evidence for more pronounced acute axonal damage in inflammatory demyelinating lesions from children compared to adults.
authors.affiliation: Department of Neuropathology, University Medical Center, Georg August University, Göttingen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Pfeifenbring
authors.forename: Reem F
authors.initials: RF
authors.lastname: Bunyan
authors.forename: Imke
authors.initials: I
authors.lastname: Metz
authors.forename: Christian
authors.initials: C
authors.lastname: Röver
authors.forename: Peter
authors.initials: P
authors.lastname: Huppke
authors.forename: Jutta
authors.initials: J
authors.lastname: Gärtner
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Lucchinetti
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001369:Axons / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000453:epidemiology*; D055815:Young Adult