Axonal loss in normal-appearing white matter in a patient with acute MS

Neurology. 2001 Oct 9;57(7):1248-52. doi: 10.1212/wnl.57.7.1248.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adult
  • Axons / pathology*
  • Axons / ultrastructure
  • Brain Stem / pathology
  • Fatal Outcome
  • Humans
  • Male
  • Microscopy, Electron
  • Multiple Sclerosis, Relapsing-Remitting / pathology*
  • Myelin Sheath / pathology
  • Myelin Sheath / ultrastructure
  • Spinal Cord / pathology