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From the Departments of Neurology (A.M.P., C.V., I.B., B.C.), University Hospital La Fe; Physical-Chemistry and CIBER Bioengineering, Biomaterials and Nanomedicine (M.C.M.-B., B.M.-G., B.C.), University of Valencia, Burjassot; Physiology (A.M.), University of Valencia; Neurology (F.C.), University Hospital Clínico; and Radiology (M.C.M.-B., L.M.-B.), Magnetic Resonance Imaging, Hospital Quirón, Valencia, Spain.
Address correspondence and reprint requests to Dr. Ana M. Pascual, Department of Neurology, Hospital Universitario La Fe, Avda. Campanar 21, at Valencia. E. 46009, Valencia, Spain med004201{at}saludalia.com
Objective: To assess the relationship between the spectroscopically measured axonal damage in the normal-appearing white matter of the brainstem, the total brain T2-hyperintense lesion volume (T2LV), and disability in patients with early relapsing–remitting multiple sclerosis (RRMS).
Methods: Forty-three RRMS patients and 10 sex- and age-matched healthy controls were prospectively studied for 2 years. T2-weighted magnetic resonance (MR) images and proton MR spectroscopy were acquired at the time of recruitment and at year 2. Brainstem was considered, where large tracts join together, as a suitable region to detect early axonal damage. The T2LV was calculated with a semiautomatic program; N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) resonances areas were integrated with the jMRUI program, and the ratios were calculated for the sum of the volume elements represented at brainstem.
Results: The basal NAA/Cho ratio was significantly decreased in patients compared with controls. After 2-year follow-up, there was a decrease in the NAA/Cho (–9%; p = 0.002) and NAA/Cr (–13%; p = 0.001) ratios, and an increase in the T2LV (19%; p = 0.043) in multiple sclerosis patients, whereas control subjects had no significant metabolic changes. Significant NAA/Cr ratio decreases were observed in both patients, with and without relapses, whereas T2LV only increased in patients with relapses. The final Expanded Disability Status Scale (EDSS) score correlated with T2LV at baseline, but no significant correlations were found between metabolic values, T2LV change, or EDSS score over the study period.
Conclusions: Our data reveal an early and progressive axonal damage in relapsing–remitting multiple sclerosis. Axonal loss and T2 lesion volume seem to be at least partly dissociated processes in early stages of the disease.
Supported by a grant from Serono Laboratories and partial financial support from the following national projects: ISC III 2003-G03/185, ISC III PI052695, SAF 2004-06297, and SAF 2004-20971-E.
Disclosure: The authors report no conflicts of interest.
Received July 26, 2006. Accepted in final form February 9, 2007.
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