AXONAL DAMAGE CORRELATES WITH DISABILITY IN PATIENTS WITH RELAPSING-REMITTING MULTIPLE-SCLEROSIS - RESULTS OF A LONGITUDINAL MAGNETIC-RESONANCE SPECTROSCOPY STUDY

It has been difficult to establish a strong correlation between total brain T-2-weighted lesion volume on MRI and clinical disability in mul tiple sclerosis, in part because of the lack of pathological specifici ty of T-2-weighted MRI signal changes. Proton magnetic resonance spect roscopy studies have shown that measurements of the resonance intensit y of N-acetylaspartate (which is localized exclusively in neurons and neuronal processes in the mature brain) can provide a specific index o f axonal damage or dysfunction. Here we report a 30-month longitudinal study of 29 patients with multiple sclerosis who had either a relapsi ng or a secondary progressive clinical course, Conventional brain MRI and single-voxel proton magnetic resonance spectroscopy examinations w ere obtained at intervals of 6-8 months with concurrent clinical evalu ation. At the onset of the study, the brain N-acetylaspartate : creati ne resonance intensity ratio was abnormally low for the whole group of patients (control mean = 2.93 +/- 0.2, patient mean = 2.56 +/- 0.4, P < 0.005). There were no significant differences between the relapsing and secondary progressive subgroups. Over the follow-up period, there was a trend towards a decrease (8%) in the brain N-acetylaspartate: c reatine ratio for the 11 relapsing patients and a significant (P < 0.0 01) correlation between changes in the brain N-acetyl-aspartate : crea tine ratio and expanded disability scale scores for the patients in th is group. This correlation was even more evident for the patients who had clinically relevant relapses during the 30 months of follow-up (se ven of 11 patients). Increases in T-2-weighted lesion volumes (35% in 30 months for the group as a whole, P < 0.0001, without differences be tween the subgroups) did not correlate with disability either in the g roup of patients as a whole or in the different subgroups. We conclude that indices of axonal damage or loss such as brain N-acetylaspartate may provide a specific measure of pathological changes relevant to di sability. Total T-2-weighted lesion volumes, although more sensitive t o changes with time than brain N-acetylaspartate, may be less relevant to understanding the progression of disability.