Brain metabolic changes suggestive of axonal damage in radiologically isolated syndrome

Neurology. 2013 Jun 4;80(23):2090-4. doi: 10.1212/WNL.0b013e318295d707. Epub 2013 May 1.


Background: The MRI incidental finding in asymptomatic subjects of brain white matter (WM) changes meeting the Barkhof criteria for the diagnosis of multiple sclerosis (MS) has been recently characterized as the radiologically isolated syndrome (RIS). This entity needs to be more specifically defined to allow risk stratification of these subjects. We used brain proton magnetic resonance spectroscopic imaging (1H-MRSI) to assess metabolic changes in an RIS population.

Methods: Twenty-three RIS subjects who were classified according to the Okuda Criteria underwent 1H-MRSI examination with a central brain (CB) volume of interest (VOI) to measure levels of N-acetylaspartate (NAA) and choline (Cho) normalized to creatine (Cr) in the whole CB-VOI, in lesional/perilesional and normal-appearing WM regions, and in the cortical gray matter (CGM). The 1H-MRSI data were compared with those of 20 demographically matched healthy controls (HC).

Results: NAA/Cr levels were significantly lower in RIS than in HC in all regions (p < 0.005 for all). No differences in Cho/Cr levels were found in either brain region. A single-subject analysis showed that NAA/Cr levels were at least 2 SDs below the HC mean in the 44% of RIS in the normal-appearing WM and in the 61% of RIS in the CGM.

Conclusion: Decreased brain NAA/Cr levels in a group of RIS subjects indicates that brain metabolic abnormalities suggestive of axonal damage can be significant even at this early disease stage. This information could be useful for stratifying RIS individuals with a high risk of progression to MS.

MeSH terms

  • Adult
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Axons / pathology*
  • Brain* / metabolism
  • Brain* / pathology
  • Choline / metabolism
  • Creatine / metabolism
  • Disease Progression
  • Female
  • Humans
  • Magnetic Resonance Spectroscopy / instrumentation
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnosis*
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis / pathology
  • Prodromal Symptoms
  • Protons*
  • Risk
  • Syndrome
  • Young Adult


  • Protons
  • Aspartic Acid
  • N-acetylaspartate
  • Creatine
  • Choline