Widespread Neuronal Dysfunction Seen Early In Relapsing-Remitting Multiple Sclerosis

Reduction in multiple sclerosis cortical grey matter of N-acetyl-aspartate is suggestive of mild but widespread neuronal dysfunction or loss occurring in the course of relapsing-remitting disease, according to researchers.

Neuronal damage and loss appear to underlie irreversible disability in multiple sclerosis (MS). However, there is uncertainty about the time of onset, location and extent of neuronal damage in the early stages of the disease.

Consequently, researchers from the Neurological Departments at the Karl-Franzens University in Graz, Austria, the Institute of Neurology in London, United Kingdom, and the Magnetic Resonance Imaging unit in Buckinghamshire, UK, designed an explorative quantitative magnetic resonance (MR) spectroscopy imaging study.

Participants included 16 patients with short duration, mild relapsing-remitting disease and 12 age-matched controls. The patients underwent studies using a short echo time proton MR spectroscope imaging (¹H-MRSI) to quantify the concentration of the N-acetyl-aspartate neuronal marker. The data for MS patients were compared with controls and the ¹H-MRSI was obtained from a 1.5-cm-thick slice just above the lateral ventricles.

Automated measurement of absolute metabolite concentrations from lesions, normal-appearing white matter and cortical grey matter (CGM) was conducted by locally developed software combined with the Linear Combination Model.

There was significantly lower N-acetyl-aspartate and myo-inositol revealed in MS CGM than was seen in the control CGM. There was also a lower concentration of N-acetyl-aspartate and increased myo-inositol than control white matter in MS normal-appearing white matter. However, lesions revealed a more marked reduction in N-acetyl-aspartate and increases in myo-inositol.

Researchers concluded that a larger cohort should confirm their preliminary findings. In addition, follow-up studies are necessary to determine the prognostic and pathophysiological significance of the early changes.


Journal of Neurology 2001 Vol 248 No 2 pp 131-138. "Preliminary evidence for neuronal damage in cortical grey matter and normal appearing white matter in short duration relapsing-remitting multiple sclerosis: a quantitative MR spectroscopic imaging study"

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