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Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2004 Jan;75(1):103–109.

Multiple regional 1H-MR spectroscopy in multiple system atrophy: NAA/Cr reduction in pontine base as a valuable diagnostic marker

H Watanabe 1, H Fukatsu 1, M Katsuno 1, M Sugiura 1, K Hamada 1, Y Okada 1, M Hirayama 1, T Ishigaki 1, G Sobue 1
PMCID: PMC1757481  PMID: 14707317

Abstract

Objective: We performed 1H-MR spectroscopy (1H-MRS) on multiple brain regions to determine the metabolite pattern and diagnostic utility of 1H-MRS in multiple system atrophy (MSA).

Methods: Examining single voxels at 3.0 T, we studied metabolic findings of the putamen, pontine base, and cerebral white matter in 24 MSA patients (predominant cerebellar ataxia (MSA-C), n = 13), parkinsonism (MSA-P), n = 11), in 11 age and duration matched Parkinson's disease patients (PD) and in 18 age matched control subjects.

Results: The N-acetylaspartate to creatine ratio (NAA/Cr) in MSA patients showed a significant reduction in the pontine base (p<0.0001) and putamen (p = 0.02) compared with controls. NAA/Cr in cerebral white matter also tended to decline in long standing cases. NAA/Cr reduction in the pontine base was prominent in both MSA-P (p<0.0001) and MSA-C (p<0.0001), and putaminal NAA/Cr reduction was significant in MSA-P (p = 0.009). It was also significant in patients who were in an early phase of their disease, and in those who showed no ataxic symptoms or parkinsonism, or did not show any MRI abnormality of the "hot cross bun" sign or hyperintense putaminal rims. NAA/Cr in MSA-P patients was significantly reduced in the pontine base (p = 0.001) and putamen (p = 0.002) compared with PD patients. The combined 1H-MRS in the putamen and pontine base served to distinguish patients with MSA-P from PD more clearly.

Conclusions:1H-MRS showed widespread neuronal and axonal involvement in MSA. The NAA/Cr reduction in the pontine base proved highly informative in the early diagnosis of MSA prior to MRI changes and even before any clinical manifestation of symptoms.

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Selected References

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  1. Abe K., Terakawa H., Takanashi M., Watanabe Y., Tanaka H., Fujita N., Hirabuki N., Yanagihara T. Proton magnetic resonance spectroscopy of patients with parkinsonism. Brain Res Bull. 2000 Aug;52(6):589–595. doi: 10.1016/s0361-9230(00)00321-x. [DOI] [PubMed] [Google Scholar]
  2. Bhakoo K. K., Pearce D. In vitro expression of N-acetyl aspartate by oligodendrocytes: implications for proton magnetic resonance spectroscopy signal in vivo. J Neurochem. 2000 Jan;74(1):254–262. doi: 10.1046/j.1471-4159.2000.0740254.x. [DOI] [PubMed] [Google Scholar]
  3. Bjartmar Carl, Battistuta Jan, Terada Nobuo, Dupree Erica, Trapp Bruce D. N-acetylaspartate is an axon-specific marker of mature white matter in vivo: a biochemical and immunohistochemical study on the rat optic nerve. Ann Neurol. 2002 Jan;51(1):51–58. doi: 10.1002/ana.10052. [DOI] [PubMed] [Google Scholar]
  4. Bomsdorf H., Helzel T., Kunz D., Röschmann P., Tschendel O., Wieland J. Spectroscopy and imaging with a 4 tesla whole-body MR system. NMR Biomed. 1988 Jun;1(3):151–158. doi: 10.1002/nbm.1940010308. [DOI] [PubMed] [Google Scholar]
  5. Calne D. B., Snow B. J., Lee C. Criteria for diagnosing Parkinson's disease. Ann Neurol. 1992;32 (Suppl):S125–S127. doi: 10.1002/ana.410320721. [DOI] [PubMed] [Google Scholar]
  6. Castellani R. Multiple system atrophy: clues from inclusions. Am J Pathol. 1998 Sep;153(3):671–676. doi: 10.1016/S0002-9440(10)65608-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Clarke C. E., Lowry M. Basal ganglia metabolite concentrations in idiopathic Parkinson's disease and multiple system atrophy measured by proton magnetic resonance spectroscopy. Eur J Neurol. 2000 Nov;7(6):661–665. doi: 10.1046/j.1468-1331.2000.00111.x. [DOI] [PubMed] [Google Scholar]
  8. Clarke C. E., Lowry M. Systematic review of proton magnetic resonance spectroscopy of the striatum in parkinsonian syndromes. Eur J Neurol. 2001 Nov;8(6):573–577. doi: 10.1046/j.1468-1331.2001.00308.x. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Davie C. The role of spectroscopy in parkinsonism. Mov Disord. 1998 Jan;13(1):2–4. doi: 10.1002/mds.870130104. [DOI] [PubMed] [Google Scholar]
  11. Federico F., Simone I. L., Lucivero V., Iliceto G., De Mari M., Giannini P., Mezzapesa D. M., Tarantino A., Lamberti P. Proton magnetic resonance spectroscopy in Parkinson's disease and atypical parkinsonian disorders. Mov Disord. 1997 Nov;12(6):903–909. doi: 10.1002/mds.870120611. [DOI] [PubMed] [Google Scholar]
  12. Federico F., Simone I. L., Lucivero V., Mezzapesa D. M., de Mari M., Lamberti P., Petruzzellis M., Ferrari E. Usefulness of proton magnetic resonance spectroscopy in differentiating parkinsonian syndromes. Ital J Neurol Sci. 1999 Aug;20(4):223–229. doi: 10.1007/s100720050035. [DOI] [PubMed] [Google Scholar]
  13. Gatto E. M., Zurrú M. C., Rugilo C., Mitre S., Pardal A. M., Martinez M., Pardal M. M. Focal myoclonus associated with posterior thalamic hematoma. Mov Disord. 1998 Jan;13(1):182–184. doi: 10.1002/mds.870130138. [DOI] [PubMed] [Google Scholar]
  14. Gilman S., Low P. A., Quinn N., Albanese A., Ben-Shlomo Y., Fowler C. J., Kaufmann H., Klockgether T., Lang A. E., Lantos P. L. Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci. 1999 Feb 1;163(1):94–98. doi: 10.1016/s0022-510x(98)00304-9. [DOI] [PubMed] [Google Scholar]
  15. Graham J. G., Oppenheimer D. R. Orthostatic hypotension and nicotine sensitivity in a case of multiple system atrophy. J Neurol Neurosurg Psychiatry. 1969 Feb;32(1):28–34. doi: 10.1136/jnnp.32.1.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gruetter R., Weisdorf S. A., Rajanayagan V., Terpstra M., Merkle H., Truwit C. L., Garwood M., Nyberg S. L., Uğurbil K. Resolution improvements in in vivo 1H NMR spectra with increased magnetic field strength. J Magn Reson. 1998 Nov;135(1):260–264. doi: 10.1006/jmre.1998.1542. [DOI] [PubMed] [Google Scholar]
  17. Hetherington H. P., Pan J. W., Chu W. J., Mason G. F., Newcomer B. R. Biological and clinical MRS at ultra-high field. NMR Biomed. 1997 Dec;10(8):360–371. doi: 10.1002/(sici)1099-1492(199712)10:8<360::aid-nbm477>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  18. Konagaya M., Sakai M., Matsuoka Y., Goto Y., Yoshida M., Hashizume Y. Pathological correlate of the slitlike changes on MRI at the putaminal margin in multiple system atrophy. J Neurol. 1999 Feb;246(2):142–143. doi: 10.1007/s004150050323. [DOI] [PubMed] [Google Scholar]
  19. Konagaya M., Sakai M., Matsuoka Y., Konagaya Y., Hashizume Y. Multiple system atrophy with remarkable frontal lobe atrophy. Acta Neuropathol. 1999 Apr;97(4):423–428. doi: 10.1007/s004010051008. [DOI] [PubMed] [Google Scholar]
  20. Kraft E., Schwarz J., Trenkwalder C., Vogl T., Pfluger T., Oertel W. H. The combination of hypointense and hyperintense signal changes on T2-weighted magnetic resonance imaging sequences: a specific marker of multiple system atrophy? Arch Neurol. 1999 Feb;56(2):225–228. doi: 10.1001/archneur.56.2.225. [DOI] [PubMed] [Google Scholar]
  21. Lantos P. L. The definition of multiple system atrophy: a review of recent developments. J Neuropathol Exp Neurol. 1998 Dec;57(12):1099–1111. doi: 10.1097/00005072-199812000-00001. [DOI] [PubMed] [Google Scholar]
  22. Litvan I., Goetz C. G., Jankovic J., Wenning G. K., Booth V., Bartko J. J., McKee A., Jellinger K., Lai E. C., Brandel J. P. What is the accuracy of the clinical diagnosis of multiple system atrophy? A clinicopathologic study. Arch Neurol. 1997 Aug;54(8):937–944. doi: 10.1001/archneur.1997.00550200007003. [DOI] [PubMed] [Google Scholar]
  23. Moffett J. R., Namboodiri M. A., Cangro C. B., Neale J. H. Immunohistochemical localization of N-acetylaspartate in rat brain. Neuroreport. 1991 Mar;2(3):131–134. doi: 10.1097/00001756-199103000-00005. [DOI] [PubMed] [Google Scholar]
  24. Quinn N. Multiple system atrophy--the nature of the beast. J Neurol Neurosurg Psychiatry. 1989 Jun;Suppl:78–89. doi: 10.1136/jnnp.52.suppl.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ross B., Michaelis T. Clinical applications of magnetic resonance spectroscopy. Magn Reson Q. 1994 Dec;10(4):191–247. [PubMed] [Google Scholar]
  26. Rudkin T. M., Arnold D. L. Proton magnetic resonance spectroscopy for the diagnosis and management of cerebral disorders. Arch Neurol. 1999 Aug;56(8):919–926. doi: 10.1001/archneur.56.8.919. [DOI] [PubMed] [Google Scholar]
  27. Savoiardo M., Strada L., Girotti F., Zimmerman R. A., Grisoli M., Testa D., Petrillo R. Olivopontocerebellar atrophy: MR diagnosis and relationship to multisystem atrophy. Radiology. 1990 Mar;174(3 Pt 1):693–696. doi: 10.1148/radiology.174.3.2305051. [DOI] [PubMed] [Google Scholar]
  28. Schrag A., Good C. D., Miszkiel K., Morris H. R., Mathias C. J., Lees A. J., Quinn N. P. Differentiation of atypical parkinsonian syndromes with routine MRI. Neurology. 2000 Feb 8;54(3):697–702. doi: 10.1212/wnl.54.3.697. [DOI] [PubMed] [Google Scholar]
  29. Simmons M. L., Frondoza C. G., Coyle J. T. Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience. 1991;45(1):37–45. doi: 10.1016/0306-4522(91)90101-s. [DOI] [PubMed] [Google Scholar]
  30. Sobue G., Terao S., Kachi T., Ken E., Hashizume Y., Mitsuma T., Takahashi A. Somatic motor efferents in multiple system atrophy with autonomic failure: a clinico-pathological study. J Neurol Sci. 1992 Oct;112(1-2):113–125. doi: 10.1016/0022-510x(92)90140-g. [DOI] [PubMed] [Google Scholar]
  31. Terakawa H., Abe K., Watanabe Y., Nakamura M., Fujita N., Hirabuki N., Yanagihara T. Proton magnetic resonance spectroscopy (1H MRS) in patients with sporadic cerebellar degeneration. J Neuroimaging. 1999 Apr;9(2):72–77. doi: 10.1111/jon19999272. [DOI] [PubMed] [Google Scholar]
  32. Urenjak J., Williams S. R., Gadian D. G., Noble M. Specific expression of N-acetylaspartate in neurons, oligodendrocyte-type-2 astrocyte progenitors, and immature oligodendrocytes in vitro. J Neurochem. 1992 Jul;59(1):55–61. doi: 10.1111/j.1471-4159.1992.tb08875.x. [DOI] [PubMed] [Google Scholar]
  33. Watanabe Hirohisa, Saito Yufuko, Terao Shinichi, Ando Tetsuo, Kachi Teruhiko, Mukai Eiichiro, Aiba Ikuko, Abe Yuji, Tamakoshi Akiko, Doyu Manabu. Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients. Brain. 2002 May;125(Pt 5):1070–1083. doi: 10.1093/brain/awf117. [DOI] [PubMed] [Google Scholar]
  34. Wenning G. K., Ben-Shlomo Y., Magalhães M., Daniel S. E., Quinn N. P. Clinicopathological study of 35 cases of multiple system atrophy. J Neurol Neurosurg Psychiatry. 1995 Feb;58(2):160–166. doi: 10.1136/jnnp.58.2.160. [DOI] [PMC free article] [PubMed] [Google Scholar]

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