Abstract
Purpose
To prospectively investigate metabolic changes in the normal-appearing white matter (NAWM) of patients presenting with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) and to correlate these changes to conventional MR imaging findings in terms of MR imaging criteria.
Materials and methods
Multisequence MR imaging of the brain and 1H-MR spectroscopy of the parietal NAWM were performed in 31 patients presenting with CIS and in 20 controls using a 3. 0 T MR system. MR imaging criteria and International Panel criteria were assessed based on imaging, clinical and paraclinical results. Metabolite ratios and absolute concentrations of N-acetyl-aspartate (tNAA), myoinositol (Ins), choline (Cho), and total creatine (tCr) were determined. The metabolite concentrations were correlated with the fulfilled MR imaging criteria.
Results
In comparison to the control group, the CIS group showed significantly decreased mean tNAA concentrations (–8. 1%, p = 0. 012). Significant changes could not be detected regarding Ins, tCr and Cho. No significant correlations between absolute metabolite concentrations and MR imaging criteria were observed. Patients with and without a lesion dissemination in space showed no significant differences of their metabolite concentrations.
Conclusion
As assessed by 1H-MRS a significant axonal damage already occurs during the first demyelinating episode in patients with CIS. Conventional MR imaging in terms of diagnostic imaging criteria does not significantly reflect NAWM disease activity in terms of metabolic alterations detected by 1H-MR spectroscopy.
Article PDF
Similar content being viewed by others
Explore related subjects
Discover the latest articles, news and stories from top researchers in related subjects.Avoid common mistakes on your manuscript.
References
Ge Y (2006) Multiple sclerosis: the role of MR imaging. AJNR Am J Neuroradiol 27:1165–1176
Miller DH, Thompson AJ, Filippi M (2003) Magnetic resonance studies of abnormalities in the normal appearing white matter and grey matter in multiple sclerosis. J Neurol 250:1407–1419
Minneboo A, Barkhof F, Polman CH, et al. (2004) Infratentorial lesions predict long-term disability in patients with initial findings suggestive of multiple sclerosis. Arch Neurol 61:217–221
Bakshi R, Ariyaratana S, Benedict RH, Jacobs L (2001) Fluid-attenuated inversion recovery magnetic resonance imaging detects cortical and juxtacortical multiple sclerosis lesions. Arch Neurol 58:742–748
Barkhof F, Filippi M, Miller DH, et al. (1997) Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis. Brain 120:2059–2069
Tintoré M, Rovira A, Martinez MJ, et al. (2000) Isolated demyelinating syndromes: comparison of different MR imaging criteria to predict conversion to clinically definite multiple sclerosis. AJNR Am J Neuroradiol 21:702–706
Polman CH, Reingold SC, Edan G, et al. (2005) Diagnostic Criteria for Multiple Sclerosis: 2005 Revisions to the "Mc- Donald Criteria". Ann Neurol 58:840–846
Chard DT, Griffin CM, McLean MA, et al. (2002) Brain metabolite changes in cortical grey and normal-appearing white matter in clinically early relapsing remitting multiple sclerosis. Brain 125:2342–2352
Fernando KTM, Tozer DJ, Mizkiel KA, et al. (2005) Magnetization transfer histograms in clinically isolated syndromes suggestive of multiple sclerosis. Brain 128:2911–2925
Ge Y, Grossman RI Udupa JK, et al. (2001) Magnetization transfer ratio histogram analysis of gray matter in relapsing-remitting multiple sclerosis. AJNR Am J Neuroradiol 22:470–475
Rovaris M, Gass A, Bammer R, et al. (2005) Diffusion MRI in multiple sclerosis. Neurology 65:1526–1532
Vrenken H, Pouwels PJW, Geurts JJG, Knol DL, Polman CH, Barkhof F, Castelijns JA (2006) Altered diffusion tensor in multiple sclerosis normal-appearing brain tissue: cortical diffusion seem related to clinical deterioration. J Magn Reson Imaging 23:628–636
Parry A, Clare S, Jenkinson M, Smith S, Palace J, Matthews PM (2002) White matter and lesion T1 relaxation times increase in parallel and correlate with disability in multiple sclerosis. J Neurol 249:1279–1286
Vrenken H, Rombouts SARB, Pouwels PJW, Barkhof F (2006) Voxel-based analysis of quantitative T1 maps demonstrates that multiple sclerosis acts throughout the normal-appearing white matter. AJNR Am J Neuroradiol 27:868–874
Leary SM, Davie CA, Parker GJ, et al. (1999) 1H magnetic resonance spectroscopy of normal appearing white matter in primary progressive multiple sclerosis. J Neurol 246:1023–1026
De Stefano N, Matthews PM, Fu L, et al. (1998) Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study. Brain 121:1469–1477
De Stefano N, Narayanan S, Francis GS, et al. (2001) Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability. Arch Neurol 58:65–70
Sastre-Garriga J, Ingle GT, Chard DT, et al. (2005) Metabolite changes in normal- appearing gray and white matter are linked with disability in early primary progressive multiple sclerosis. Arch Neurol 62:569–573
Bitsch A, Bruhn H, Vougioukas V, et al. (1999) Inflammatory CNS demyelination: histopathologic correlation with in vivo quantitative proton MR spectroscopy. AJNR Am J Neuroradiol 20:1619–1627
Kapeller P, McLean MA, Griffin CM, et al. (2001) Preliminary evidence for neuronal damage in cortical grey and normal appearing white matter in short duration relapsing-remitting multiple sclerosis: a quantitative MR spectroscopic imaging study. J Neurol 248:131–138
Kapeller P, Brex PA, Chard D, et al. (2002) Quantitative 1H MRS imaging 14 years after presenting with clinically isolated syndromes suggestive of multiple sclerosis. Mult Scler 8:207–210
Vrenken H, Barkhof F, Uitdehaag BMJ, Castelijns JA, Polman CH, Pouwels PJW (2005) MR spectroscopic evidence of glial increase but not for neuro-axonal damage in MS normalappearing white matter. Magn Reson Med 53:256–266
Srinivasan R, Sailasuta N, Hurd R, Nelson S, Pelletier D (2005) Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3T Brain 128:1016–1025
Tourbah A, Stievenart JL, Abanou A, et al. (1999) Normal-appearing white matter in optic neuritis and multiple sclerosis: a comparative proton spectroscopy study. Neuroradiology 41:738–743
Fernando KTM, McLean MA, Chard DT, et al. (2004) Elevated white matter myo-inositol in clinical isolated syndromes suggestive of multiple sclerosis. Brain 127:1361–1369
Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452
Simon JH, Li D, Traboulsee A, et al. (2006) Standardized MR Imaging Protocol for Multiple Sclerosis: Consortium of MS Centers Consensus Guidelines. AJNR Am J Neuroradiol 27:455–461
Korteweg T, Uitdehaag BMJ, Knol DL, et al. (2007) Interobserver agreement on the radiological criteria of the International Panel on the diagnosis of multiple sclerosis. Eur Radiol 17:67–71
Wiedermann D, Schuff N, Matson GB, et al. (2001) Short echo time multislice proton magnetic resonance spectroscopic imaging in human brain: metabolite distributions and reliability. Magn Reson Imaging 19:1073–1080
Naressi A, Couturier C, Devos JM, et al. (2001) Java-based graphical user interface for the MRUI quantitation package. MAGMA 12:141–152
Vanhamme L, van den Boogaart A, van Huffel S (1997) Improved method for accurate and efficient quantification of MRS data with use of prior knowledge. J Magn Reson 129:35–43
Wattjes MP, Harzheim M, Lutterbey GG, Klotz L, Schild HH, Träber F (2007) Axonal damage but no increased glial cell activity in the normal-appearing white matter of patients with clinically isolated syndromes suggestive of multiple sclerosis using high field magnetic resonance spectroscopy. AJNR Am J Neuroradiol 28:1517–1522
Keiper MD, Grossmann RI, Hirsch JA, et al. (1998) MR identification of white matter abnormalities in multiple sclerosis: a comparison between 1. 5T and 4T AJNR Am J Neuroradiol 19:1489–1493
Wattjes MP, Lutterbey GG, Harzheim M, Gieseke J, Träber F, Klotz L, Klockgether T, Schild HH (2006) Higher sensitivity in the detection of inflammatory brain lesions in patients with clinically isolated syndromes suggestive of multiple sclerosis using high field MRI: an intraindividual comparison of 1. 5T with 3. 0T Eur Radiol 16:2067–2073
Wattjes MP, Harzheim M, Kuhl CK, et al. (2006) Does High-field MRI have an influence on the classification of patients with clinically isolated syndromes according to current diagnostic magnetic resonance imaging criteria for multiple sclerosis? AJNR Am J Neuroradiol 27:1794–1798
Srinivasan R, Vignerion D, Sailasuta N, Hurd R, Nelson S (2004) A comparative study of myo-inositol quantification using LCmodel at 1. 5 T and 3. 0 T with 3 D 1H proton spectroscopic imaging of the human brain. Magn Reson Imaging 22:523–528
Gonen O, Gruber S, Mi BS, et al. (2001) Multivoxel 3D proton spectroscopy in the brain at 1. 5 versus 3. 0 T: signal-tonoise ratio and resolution comparison. AJNR Am J Neuroradiol 22:1727–1731
Filippi M, Bozzali M, Rovaris M, et al. (2003) Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis. Brain 126:433–437
Filippi M, Rovaris M, Inglese M, et al. (2004) Interferon beta-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomized, double blind, placebo-controlled trial. Lancet 364:1489–1496
Brex PA, Ciccarelli O, O’ Riordan JI, Sailer M, Thompson AJ, Miller DH (2002) A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med 346:158–164
Van Au Duong M, Audoin B, Fur YL, et al. (2007) Relationships between gray matter metabolic abnormalities and white matter inflammation in patients at the very early stage of MSA MRSI study. J Neurol 254:914–923
Tiberio M, Chard DT, Altmann DR, et al. (2006) Metabolite changes in early relapsing-remitting multiple sclerosis. A two year follow-up study. J Neurol 253:224–230
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wattjes, M.P., Harzheim, M., Lutterbey, G.G. et al. High field MR imaging and 1H-MR spectroscopy in clinically isolated syndromes suggestive of multiple sclerosis. J Neurol 255, 56–63 (2008). https://doi.org/10.1007/s00415-007-0666-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-007-0666-9