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MRI lesion volume heterogeneity in primary progressive MS in relation with axonal damage and brain atrophy
  1. D Pelletier1,
  2. S J Nelson2,
  3. J Oh2,
  4. J P Antel3,
  5. M Kita1,
  6. S S Zamvil1,
  7. D E Goodkin1
  1. 1Department of Neurology, University of California at San Francisco, CA, USA
  2. 2Department of Radiology, University of California at San Francisco
  3. 3Department of Neurology, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
  1. Correspondence to:
 Dr D Pelletier, University of California at San Francisco, Multiple Sclerosis Center, 350 Parnassus Avenue, Suite 908, San Francisco, CA 94117, USA;


Objectives: To investigate whether axonal damage in primary progressive (PP) multiple sclerosis (MS), as measured by proton magnetic resonance spectroscopy (HMRS) imaging and brain atrophy, is a function of T2 weighted brain lesion volume.

Methods: 34 PP MS patients were divided into two categories: low (<3 cm3, n = 18) or high (≥3 cm3, n = 16) T2 lesion load (LL). An Index of Brain Atrophy (IBA) was calculated and HMRS metabolite ratios were derived from a central brain area centred at the corpus callosum.

Results: Patient groups did not differ with regard to clinical characteristics and showed lower mean IBA and mean N-acetylaspartate:creatinine (NAA:Cr) ratios compared to healthy controls.

Conclusion: PP patients with low and high brain T2LL have detectable brain atrophy and NAA:Cr reduction compared to healthy controls. In PP MS, T2 lesions alone are insufficient to explain the presence of brain atrophy and decrease in NAA:Cr.

  • N-acetylaspartate
  • proton nuclear magnetic resonance spectroscopy
  • brain atrophy
  • primary progressive multiple sclerosis
  • CB, central brain
  • COV, coefficient of variation
  • Cr, creatinine
  • CSG, cerebrospinal fluid
  • EDSS, Expanded Disability Status Score
  • HMRS, proton magnetic resonance spectroscopy
  • IBA, Index of Brain Atrophy
  • LL, lesion load
  • MRI, magnetic resonance imaging
  • MS, multiple sclerosis
  • NAA, N-acetylaspartate
  • NAWM, normal appearing white matter
  • PD, proton density
  • PP, primary progressive
  • ROI, region of interest
  • RR, relapse remitting
  • SP, secondary progressive

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  • Competing interests: DE Goodkin was an employee of Immunex Corporation at the time of submission of this manuscript