Abstract:
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Purpose: Multiple sclerosis (MS) is radiologically characterized in the brain by lesion formation, atrophy and progressive neuronal cell deficits. The first two processes can be assessed in vivo with conventional MRI and the third obtained indirectly, from the level of the amino acid derivative N-acetylaspartate (NAA) which is almost exclusive to neuronal cells, with proton magnetic resonance spectroscopy (1H-MRS). Our goal was to quantify the relationships between these two markers and disease duration in order to identify the earlier pathogenesis.
Methods and Materials: Cross-sectional global macroscopic and microscopic deficits were evaluated via, (a) relative atrophy from MRI; and (b) whole brain N-acetylaspartate (WBNAA) concentration from non-localized 1H-MRS, respectively. Since the amount of NAA in the brain is divided by the brain volume (from MRI segmentation), WBNAA concentration is a metric suitable for cross-sectional comparisons. Both metrics were obtained from 42 patients (30 women, 12 men) of median age 38 years (24 - 55) with 0 - 12 years (average 6) of relapsing-remitting (RR) MS disease duration and median Expanded Disability Status Scale (EDSS) score of 1.5 (range 0 - 6).
Results: Both atrophy and WBNAA exhibited significant decline with disease duration, at 0.5% and 1.8% per year, p=0.033 and 0.005, respectively. Neither metric correlated with the other or with the EDSS score.
Conclusion: The x3.6-fold disparity between the rates of the two processes suggests that metabolic neuronal/axonal dysfunction (NAA) in RR MS precedes non-reversible parenchyma loss, not its consequence, i.e., it is an earlier, more sensitive, more specific metric of ongoing disease activity. Therefore, early treatment monitoring and drug development should probably focus on NAA not just on parenchymal atrophy or the various lesion loads.
Questions about this event email: ODED.GONEN@MED.NYU.EDU
Gonen PhD, O,
Neuronal Cell Injury Precedes Brain Atrophy in Multiple Sclerosis. Radiological Society of North America 2003 Scientific Assembly and Annual Meeting, November 30 - December 5, 2003 ,Chicago IL.
http://archive.rsna.org/2003/3102085.html
