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Quantitative 1H MRS imaging 14 years after presenting with a clinically isolated syndrome suggestive of multiple sclerosis

NMR Research Unit, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK, Department of Neurology, Karl-Franzens University, Auenbruggerplatz 22, A-8036 Graz, Austria

P A Brex

NMR Research Unit, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK

D Chard

NMR Research Unit, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK

C Dalton

NMR Research Unit, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK

C M Griffin

NMR Research Unit, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK

M A McLean

NMR Research Unit, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK, National Society for Epilepsy MRI Unit, Chalfont St. Peter, Bucks, UK

G JM Parker

NMR Research Unit, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK

A J Thompson

NMR Research Unit, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK

D H Miller

NMR Research Unit, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK, d.miller{at}ion.ucl.ac.uk

Clinically isolated syndromes (CIS) are events suggestive for emerging multiple sclerosis (MS). A majority of patients develop MS within months or years whilst others remain clinically isolated. The goal of this study was to investigate whether biochemical metabolites detectable by 1H magnetic resonance spectroscopy (MRS) may serve to distinguish between these two groups. We investigated 41 patients 14 years after presentation with a CIS and 21 controls with combined quantitative short echo 1H MRS and magnetic resonance imaging (MRI) and assessed disability according to the Expanded Disability Status Scale (EDSS). At follow-up, 32 had developed MS, and 9 still had CIS. Compared with controls, MS patients demonstrated significantly higher concentrations of myo-inositol (Ins) in normal appearing white matter (NAWM) and lesions. Lesions also demonstrated a reduced N-acetyl-aspartate (NAA) level and an increase in choline-containing compounds (Cho). The NAWM Ins concentration was correlated with EDSS (r = 0.48, p = 0.005). MS normal appearing cortical grey matter (CGM) exhibited a decreased NAA. Patients who remained CIS did not differ significantly from controls in any MRS measure. Metabolite changes in normal appearing white and grey matter in MS indicate diffuse involvement of the entire MS brain, which was not seen in the persisting CIS patients. Elevated Ins in MS NAWM appeared functionally relevant. It may indicate glial cell proliferation or gliosis.

Key Words: Clinically isolated syndrome • magnetic resonance spectroscopy • multiple sclerosis

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