title: Axonal loss in normal-appearing white matter in a patient with acute MS.
abstract: BACKGROUND
  Brain imaging studies detect abnormalities in normal-appearing white matter in patients with MS.
  
  
  OBJECTIVE
  To investigate the histopathologic basis for these changes in autopsy tissue from a patient with MS with 9 months' disease duration and a terminal brain stem lesion.
  
  
  METHODS
  The brain stem and spinal cord were analyzed ultrastructurally and immunocytochemically for axons, myelin, and activated microglia/macrophages.
  
  
  RESULTS
  Pathologic findings were consistent with a terminal inflammatory demyelinated lesion at the cervicomedullary junction. The ventral spinal cord column, containing descending tracts, exhibited 22% axonal loss at segment C7, but grossly normal immunostaining for myelin. Confocal and electron microscopy revealed myelin sheaths without axonal content and initial stages of myelin degradation by activated microglia/macrophages among intact myelinated axons. Axonal number and appearance was normal in ascending sensory tracts.
  
  
  CONCLUSIONS
  These studies confirm axonal degeneration in the absence of myelin loss as one histopathologic correlate to abnormal MR findings in patients with MS.
authors.affiliation: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, OH 44195, USA.
authors.forename: C
authors.initials: C
authors.lastname: Bjartmar
authors.forename: R P
authors.initials: RP
authors.lastname: Kinkel
authors.forename: G
authors.initials: G
authors.lastname: Kidd
authors.forename: R A
authors.initials: RA
authors.lastname: Rudick
authors.forename: B D
authors.initials: BD
authors.lastname: Trapp
mesh_terms: D000208:Acute Disease; D000328:Adult; D001369:Axons / Q000473:pathology* / Q000648:ultrastructure; D001933:Brain Stem / Q000473:pathology; D017809:Fatal Outcome; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology*; D009186:Myelin Sheath / Q000473:pathology / Q000648:ultrastructure; D013116:Spinal Cord / Q000473:pathology