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Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1997 Dec;63(6):736–742. doi: 10.1136/jnnp.63.6.736

1H magnetic resonance spectroscopy of chronic cerebral white matter lesions and normal appearing white matter in multiple sclerosis

C Davie 1, G Barker 1, A Thompson 1, P Tofts 1, W McDonald 1, D Miller 1
PMCID: PMC2169838  PMID: 9416807

Abstract

OBJECTIVES—To test the hypothesis that irrecoverable neurological deficit in multiple sclerosis is associated with axonal loss.
METHODS—1H magnetic resonance spectroscopy (MRS) was carried out in a group of patients with clinically definite multiple sclerosis (n=31).
 Using this technique, the apparent concentration of NA ([NA] the sum of N-acetyl aspartate (NAA), a neuronal marker, and N-acetylaspartylglutamate has been compared in four groups of patients with multiple sclerosis classified as relapsing-remitting, secondary progressive, primary progressive, benign, and a control group.
RESULTS—In the patients with relapsing-remitting disease (n=9) there was a highly significant reduction of apparent NA (median 8.73mM, range 6.86 mM-10.74 mM, P=0.0008) from an area of high signal compared with the control group (median 11.97 mM, range 10.55mM-14.5 mM). In the patients with secondary progressive disease (n=10), there was again a highly significant reduction of apparent NA (median 7.82 mM, range 3.5 mM-10.3 mM, P=0.0003) from an area of high signal compared with the control group. In the patients with primary progressive disease (n=6) there was once again a highly significant reduction of apparent NA (median 8.83 mM, range 6.95 mM-9.89 mM, P<0.002) from an area of high signal compared with the control group. In the patients with benign disease, however, there was no significant difference in the apparent NA (median 10.5 mM, range 8.53 mM-12.8 mM, P>0.05) from an area of high signal compared with the control group. In the patients with benign disease (n=5) there was also no significant difference in the apparent NA (median 10.74 mM, range 8.58 mM-13.4 mM, P>0.3) from an area of normal appearing white matter compared with the control group. In the patients with primary progressive disease, however, there was a significant reduction of apparent NA from an area of normal appearing white matter (median 8.78 mM, range 8.7 mM-12.38 mM, P< 0.025) compared with the control group. There was a significant inverse correlation between [NA] from lesions in the patients with multiple sclerosis and disability as measured on the Kurtzke expanded disability scale score (r= -0.364, 0.05>P> 0.02).
CONCLUSION—These findings support the hypothesis that axonal loss is important in the development of disability in multiple sclerosis. They also provide evidence for axonal loss in normal appearing white matter in patients with primary progressive disease.



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Selected References

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  1. Arnold D. L., Matthews P. M., Francis G. S., O'Connor J., Antel J. P. Proton magnetic resonance spectroscopic imaging for metabolic characterization of demyelinating plaques. Ann Neurol. 1992 Mar;31(3):235–241. doi: 10.1002/ana.410310302. [DOI] [PubMed] [Google Scholar]
  2. Arnold D. L., Matthews P. M., Francis G., Antel J. Proton magnetic resonance spectroscopy of human brain in vivo in the evaluation of multiple sclerosis: assessment of the load of disease. Magn Reson Med. 1990 Apr;14(1):154–159. doi: 10.1002/mrm.1910140115. [DOI] [PubMed] [Google Scholar]
  3. Behar K. L., Ogino T. Assignment of resonance in the 1H spectrum of rat brain by two-dimensional shift correlated and J-resolved NMR spectroscopy. Magn Reson Med. 1991 Feb;17(2):285–303. doi: 10.1002/mrm.1910170202. [DOI] [PubMed] [Google Scholar]
  4. Birken D. L., Oldendorf W. H. N-acetyl-L-aspartic acid: a literature review of a compound prominent in 1H-NMR spectroscopic studies of brain. Neurosci Biobehav Rev. 1989 Spring;13(1):23–31. doi: 10.1016/s0149-7634(89)80048-x. [DOI] [PubMed] [Google Scholar]
  5. Chong W. K., Sweeney B., Wilkinson I. D., Paley M., Hall-Craggs M. A., Kendall B. E., Shepard J. K., Beecham M., Miller R. F., Weller I. V. Proton spectroscopy of the brain in HIV infection: correlation with clinical, immunologic, and MR imaging findings. Radiology. 1993 Jul;188(1):119–124. doi: 10.1148/radiology.188.1.8099750. [DOI] [PubMed] [Google Scholar]
  6. Christiansen P., Henriksen O., Stubgaard M., Gideon P., Larsson H. B. In vivo quantification of brain metabolites by 1H-MRS using water as an internal standard. Magn Reson Imaging. 1993;11(1):107–118. doi: 10.1016/0730-725x(93)90418-d. [DOI] [PubMed] [Google Scholar]
  7. Confavreux C., Aimard G., Devic M. Course and prognosis of multiple sclerosis assessed by the computerized data processing of 349 patients. Brain. 1980 Jun;103(2):281–300. doi: 10.1093/brain/103.2.281. [DOI] [PubMed] [Google Scholar]
  8. Davie C. A., Barker G. J., Webb S., Tofts P. S., Thompson A. J., Harding A. E., McDonald W. I., Miller D. H. Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss. Brain. 1995 Dec;118(Pt 6):1583–1592. doi: 10.1093/brain/118.6.1583. [DOI] [PubMed] [Google Scholar]
  9. Davie C. A., Hawkins C. P., Barker G. J., Brennan A., Tofts P. S., Miller D. H., McDonald W. I. Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions. Brain. 1994 Feb;117(Pt 1):49–58. doi: 10.1093/brain/117.1.49. [DOI] [PubMed] [Google Scholar]
  10. Davie C. A., Wenning G. K., Barker G. J., Tofts P. S., Kendall B. E., Quinn N., McDonald W. I., Marsden C. D., Miller D. H. Differentiation of multiple system atrophy from idiopathic Parkinson's disease using proton magnetic resonance spectroscopy. Ann Neurol. 1995 Feb;37(2):204–210. doi: 10.1002/ana.410370211. [DOI] [PubMed] [Google Scholar]
  11. Davies S. E., Newcombe J., Williams S. R., McDonald W. I., Clark J. B. High resolution proton NMR spectroscopy of multiple sclerosis lesions. J Neurochem. 1995 Feb;64(2):742–748. doi: 10.1046/j.1471-4159.1995.64020742.x. [DOI] [PubMed] [Google Scholar]
  12. De Stefano N., Matthews P. M., Antel J. P., Preul M., Francis G., Arnold D. L. Chemical pathology of acute demyelinating lesions and its correlation with disability. Ann Neurol. 1995 Dec;38(6):901–909. doi: 10.1002/ana.410380610. [DOI] [PubMed] [Google Scholar]
  13. Feinstein A., Ron M., Thompson A. A serial study of psychometric and magnetic resonance imaging changes in multiple sclerosis. Brain. 1993 Jun;116(Pt 3):569–602. doi: 10.1093/brain/116.3.569. [DOI] [PubMed] [Google Scholar]
  14. Frahm J., Bruhn H., Gyngell M. L., Merboldt K. D., Hänicke W., Sauter R. Localized proton NMR spectroscopy in different regions of the human brain in vivo. Relaxation times and concentrations of cerebral metabolites. Magn Reson Med. 1989 Jul;11(1):47–63. doi: 10.1002/mrm.1910110105. [DOI] [PubMed] [Google Scholar]
  15. Gideon P., Henriksen O., Sperling B., Christiansen P., Olsen T. S., Jørgensen H. S., Arlien-Søborg P. Early time course of N-acetylaspartate, creatine and phosphocreatine, and compounds containing choline in the brain after acute stroke. A proton magnetic resonance spectroscopy study. Stroke. 1992 Nov;23(11):1566–1572. doi: 10.1161/01.str.23.11.1566. [DOI] [PubMed] [Google Scholar]
  16. Grimaud J., Millar J., Thorpe J. W., Moseley I. F., McDonald W. I., Miller D. H. Signal intensity on MRI of basal ganglia in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1995 Sep;59(3):306–308. doi: 10.1136/jnnp.59.3.306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Husted C. A., Goodin D. S., Hugg J. W., Maudsley A. A., Tsuruda J. S., de Bie S. H., Fein G., Matson G. B., Weiner M. W. Biochemical alterations in multiple sclerosis lesions and normal-appearing white matter detected by in vivo 31P and 1H spectroscopic imaging. Ann Neurol. 1994 Aug;36(2):157–165. doi: 10.1002/ana.410360207. [DOI] [PubMed] [Google Scholar]
  18. Kidd D., Thompson A. J., Kendall B. E., Miller D. H., McDonald W. I. Benign form of multiple sclerosis: MRI evidence for less frequent and less inflammatory disease activity. J Neurol Neurosurg Psychiatry. 1994 Sep;57(9):1070–1072. doi: 10.1136/jnnp.57.9.1070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kidd D., Thorpe J. W., Thompson A. J., Kendall B. E., Moseley I. F., MacManus D. G., McDonald W. I., Miller D. H. Spinal cord MRI using multi-array coils and fast spin echo. II. Findings in multiple sclerosis. Neurology. 1993 Dec;43(12):2632–2637. doi: 10.1212/wnl.43.12.2632. [DOI] [PubMed] [Google Scholar]
  20. MCALPINE D. The benign form of multiple sclerosis. A study based on 241 cases seen within three years of onset and followed up until the tenth year or more of the disease. Brain. 1961 Jun;84:186–203. doi: 10.1093/brain/84.2.186. [DOI] [PubMed] [Google Scholar]
  21. Miller D. H., Austin S. J., Connelly A., Youl B. D., Gadian D. G., McDonald W. I. Proton magnetic resonance spectroscopy of an acute and chronic lesion in multiple sclerosis. Lancet. 1991 Jan 5;337(8732):58–59. doi: 10.1016/0140-6736(91)93383-k. [DOI] [PubMed] [Google Scholar]
  22. Norton W. T., Poduslo S. E., Suzuki K. Subacute sclerosing leukoencephalitis. II. Chemical studies including abnormal myelin and an abnormal ganglioside pattern. J Neuropathol Exp Neurol. 1966 Oct;25(4):582–597. doi: 10.1097/00005072-196610000-00006. [DOI] [PubMed] [Google Scholar]
  23. Olanow C. W. Magnetic resonance imaging in parkinsonism. Neurol Clin. 1992 May;10(2):405–420. [PubMed] [Google Scholar]
  24. Paty D. W., Oger J. J., Kastrukoff L. F., Hashimoto S. A., Hooge J. P., Eisen A. A., Eisen K. A., Purves S. J., Low M. D., Brandejs V. MRI in the diagnosis of MS: a prospective study with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT. Neurology. 1988 Feb;38(2):180–185. doi: 10.1212/wnl.38.2.180. [DOI] [PubMed] [Google Scholar]
  25. Phadke J. G., Best P. V. Atypical and clinically silent multiple sclerosis: a report of 12 cases discovered unexpectedly at necropsy. J Neurol Neurosurg Psychiatry. 1983 May;46(5):414–420. doi: 10.1136/jnnp.46.5.414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Poser C. M., Paty D. W., Scheinberg L., McDonald W. I., Davis F. A., Ebers G. C., Johnson K. P., Sibley W. A., Silberberg D. H., Tourtellotte W. W. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983 Mar;13(3):227–231. doi: 10.1002/ana.410130302. [DOI] [PubMed] [Google Scholar]
  27. Rao S. M., Leo G. J., Haughton V. M., St Aubin-Faubert P., Bernardin L. Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis. Neurology. 1989 Feb;39(2 Pt 1):161–166. doi: 10.1212/wnl.39.2.161. [DOI] [PubMed] [Google Scholar]
  28. Thompson A. J., Hutchinson M., Brazil J., Feighery C., Martin E. A. A clinical and laboratory study of benign multiple sclerosis. Q J Med. 1986 Jan;58(225):69–80. [PubMed] [Google Scholar]
  29. Thompson A. J., Kermode A. G., MacManus D. G., Kendall B. E., Kingsley D. P., Moseley I. F., McDonald W. I. Patterns of disease activity in multiple sclerosis: clinical and magnetic resonance imaging study. BMJ. 1990 Mar 10;300(6725):631–634. doi: 10.1136/bmj.300.6725.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Thompson A. J., Kermode A. G., Wicks D., MacManus D. G., Kendall B. E., Kingsley D. P., McDonald W. I. Major differences in the dynamics of primary and secondary progressive multiple sclerosis. Ann Neurol. 1991 Jan;29(1):53–62. doi: 10.1002/ana.410290111. [DOI] [PubMed] [Google Scholar]
  31. Thompson A. J., Miller D., Youl B., MacManus D., Moore S., Kingsley D., Kendall B., Feinstein A., McDonald W. I. Serial gadolinium-enhanced MRI in relapsing/remitting multiple sclerosis of varying disease duration. Neurology. 1992 Jan;42(1):60–63. doi: 10.1212/wnl.42.1.60. [DOI] [PubMed] [Google Scholar]
  32. Urenjak J., Williams S. R., Gadian D. G., Noble M. Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci. 1993 Mar;13(3):981–989. doi: 10.1523/JNEUROSCI.13-03-00981.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. van der Knaap M. S., van der Grond J., Luyten P. R., den Hollander J. A., Nauta J. J., Valk J. 1H and 31P magnetic resonance spectroscopy of the brain in degenerative cerebral disorders. Ann Neurol. 1992 Feb;31(2):202–211. doi: 10.1002/ana.410310211. [DOI] [PubMed] [Google Scholar]

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