title: Axonal damage in the spinal cord of MS patients occurs largely independent of T2 MRI lesions.
abstract: OBJECTIVE
  To determine the degree of axonal damage in relationship to signal abnormalities on T2-weighted high-resolution MRI in spinal cord tissue of patients with MS.
  
  
  METHODS
  Spinal cord specimens of nine patients with MS and four controls were imaged at high resolution (4.7 T) in an axial plane and scored for lesions with increased signal intensity (SI). Histopathologic sections were cut and immunostained with NE14 (neurofilament marker) and Luxol fast blue (myelin stain). For each area, axonal density and diameter were quantified; axonal irregularity, NE14 axonal staining intensity, and myelin content were semiquantitatively scored. Included were 209 areas from MS cases and 109 areas from control cases distributed over lateral, posterior, and anterior columns.
  
  
  RESULTS
  In control cases, no SI changes were found, average density of axons was 26,989/mm(2), average diameter was 1.1 micro m, and all scores for axonal irregularity, NE14 staining intensity, and myelin were normal. In MS cases, areas with increased SI were found, average axonal density was 11,807/mm(2) (p < 0.0001), and average axonal diameter 2.0 micro m (p = 0.001). Areas with high SI on MRI had lowest axonal density (average count: 10,504/mm(2); range: 3,433 to 26,325/mm(2)), largest diameter (average: 2.3 micro m; range: 1.0 to 4.0 micro m), and highest axonal irregularity and NE14 staining intensity compared to normal appearing cord tissue (NACT). However, NACT of MS cases also had lower axonal density (14,158/mm(2)) and higher average axonal diameter (1.6 micro m) than controls.
  
  
  CONCLUSIONS
  Marked axonal loss occurs in MS spinal cords, largely independent of the degree of signal abnormality on T2-weighted MRI.
authors.affiliation: Dutch MR-MS Center and Department of Radiology, VU University Medical Center, Amsterdam, the Netherlands. e.bergers@vumc.nl
authors.forename: E
authors.initials: E
authors.lastname: Bergers
authors.forename: J C J
authors.initials: JC
authors.lastname: Bot
authors.forename: C J A
authors.initials: CJ
authors.lastname: De Groot
authors.forename: C H
authors.initials: CH
authors.lastname: Polman
authors.forename: G J
authors.initials: GJ
authors.lastname: Lycklama à Nijeholt
authors.forename: J A
authors.initials: JA
authors.lastname: Castelijns
authors.forename: P
authors.initials: P
authors.lastname: van der Valk
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
mesh_terms: D000328:Adult; D000368:Aged; D001369:Axons / Q000473:pathology*; D048429:Cell Size; D004396:Coloring Agents; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D009186:Myelin Sheath / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology*
chemical_list: D004396:Coloring Agents