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Brain Advance Access originally published online on May 5, 2004
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Brain, Vol. 127, No. 6, 1361-1369, 2004
© 2004 Guarantors of Brain
doi: 10.1093/brain/awh153

Elevated white matter myo-inositol in clinically isolated syndromes suggestive of multiple sclerosis

K. T. M. Fernando1, M. A. McLean2, D. T. Chard1, D. G. MacManus1, C. M. Dalton1, K. A. Miszkiel3, R. M. Gordon1, G. T. Plant3,4, A. J. Thompson1 and D. H. Miller1

1 NMR Research Unit and 2 Epilepsy Research Unit, Institute of Neurology, 3 National Hospital for Neurology and Neurosurgery, and 4 Moorfields Eye Hospital, London, UK

Correspondence to: Kryshani T. M. Fernando, Institute of Neurology, Queen Square, London WC1N 3BG, UK. E-mail: k.fernando{at}ion.ucl.ac.uk

Normal-appearing white matter (NAWM) in established multiple sclerosis has been shown to be abnormal using a variety of magnetic resonance (MR) techniques, including proton MR spectroscopy (1H-MRS), although the stage at which these changes first appear is less clear. Using a 1.5 T scanner and single-voxel 1H-MRS [TR 3000 ms, TE 30 ms, point-resolved spectroscopy (PRESS) localization], we determined NAWM metabolite concentrations in 96 patients a mean of 19 weeks (range 12–28 weeks) after onset of a clinically isolated syndrome (CIS) suggestive of multiple sclerosis and in 44 healthy control subjects. Absolute concentrations of N-acetyl-aspartate, total creatine and phosphocreatine (Cr), choline-containing compounds, glutamate plus glutamine, and myo-inositol (Ins) were estimated automatically using the LCModel. Compared with control subjects, the concentration of Ins was elevated in CIS NAWM (mean 3.31 mM, SD 0.86 versus mean 3.82 mM, SD 1.06; P = 0.001). The increase in Ins was also seen in the patient subgroup with abnormal T2-weighted MRI (mean 3.88 mM, SD 1.10; P = 0.001) and in those who satisfied the McDonald criteria for multiple sclerosis (mean 4.04 mM, SD 1.31; P = 0.001). An increase in Cr was also observed in CIS NAWM (P = 0.023), but other metabolites did not significantly differ between the whole CIS group and control subjects. There was no significant correlation between NAWM Ins and T2 lesion load. The early increase in Ins may reflect a process of pathogenic importance in multiple sclerosis NAWM. Follow-up studies will investigate whether the increase in NAWM Ins is of prognostic importance for future relapses and disability.

Key Words: MRS, NAWM; myo-inositol; multiple sclerosis; clinically isolated syndromes

Abbreviations: CIS = clinically isolated syndrome; Cho = choline; Cr = creatine and phosphocreatine; EDSS = Expanded Disability Status Scale; Glx = glutamate and glutamine; 1H-MRS = proton magnetic resonance spectroscopy; Ins = myo-inositol; MTR = magnetization transfer ratio; NAWM = normal appearing white matter; TE = echo time; TR = repetition time; tNAA = total N-acetyl-aspartate

Received November 14, 2003. Revised January 21, 2004. Accepted January 27, 2004.


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