Chemical pathology of acute demyelinating lesions and its correlation with disability

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Abstract
We report the chemical pathological changes on magnetic resonance spectroscopic images of 4 patients, each of whom had a single large demyelinating plaque. The patients were followed from soon after the onset of the symptoms for a minimum of 7 months to a maximum of 3 1/2 years. We observed increases in the relative resonance intensities of choline‐containing compounds, lactate, and myo‐inositol inside the lesion acutely. Decreases in relative resonance intensities of N‐acetylaspartate and creatine were seen both in and around the magnetic resonance imaging—detected lesions. In all patients neurological deficits improved and creatine, lactate, and myo‐inositol resonance intensities normalized during the follow‐up. Choline compounds recovered more slowly and were still abnormally high in 1 patient after 7 months. Partial recovery of the N‐acetylaspartate resonance was seen for all patients. Evaluation of the relationships between indices of cerebral chemical pathology, brain lesion volumes, and functional disability showed highly significant negative correlations between N‐acetylaspartate resonance intensities and both brain lesion volumes (r = −0.80, p < 0.0001) and clinical disability (r = −0.73, p < 0.0001). As N‐acetylaspartate is localized solely in neurons in the adult central nervous system, our results suggest that neuronal dysfunction may be a proximate mechanism of disability even in inflammatory disorders primarily affecting myelin and oligodendroglial cells.