Spectroscopic analysis of metabolic profile in patients with relapsed multiple sclerosis

Cover Page

Cite item

Full Text

Abstract

Introduction. Managing patients with relapsing-remitting multiple sclerosis (RMS) remains a pressing issue.

Objective. To detect the reversible metabolic changes of the brain matter in patients with clinically exacerbated RMS and to follow them up after intravenous glucocorticoid (IVGC) treatment.

Materials and methods. Neurological examination and neuroimaging in the RMS patients included expanded disability status scale (EDSS) scoring, conventional brain magnetic resonance imaging (MRI), and proton nuclear magnetic resonance spectroscopy (1H-NMR spectroscopy) before and after IVGC treatment. Multivoxel 1H-NMR spectroscopy was used to assess metabolism in the centra semiovale and cingulate gyri.

Results. Based on the multivoxel 1H-NMR spectroscopy, relative metabolite concentrations in the grey and white matter statistically differed within the study cohort before and after the IVGC treatment. The N-acetylaspartate/choline ratio significantly recovered and the choline/creatine ratio decreased in the anterior cingulate gyri in 27% of patients. The brainstem function score significantly improved in the metabolic response group as compared to the non-metabolic response group.

Conclusion. We should study the potential predictors of RMS activity and the IVGC response to select the RMS relapses when pulse-therapy with IVGCs is definitely indicated. Spectroscopy may reveal RMS pathogenesis variability earlier than conventional MRI.

About the authors

Galina G. Shkilnyuk

N.P. Beсhtereva Institute of Human Brain of the Russian Academy of Sciences

Email: galinakima@mail.ru
ORCID iD: 0000-0001-7175-668X

Cand. Sci. (Med.), researcher, Laboratory of neuroimmunology

Russian Federation, 197376, St. Petersburg, Academician Pavlov Str., 9

Andrey A. Bogdan

N.P. Beсhtereva Institute of Human Brain of the Russian Academy of Sciences

Email: andrey@ihb.spb.ru
ORCID iD: 0000-0002-2836-1516

Cand. Sci. (Med.), researcher, Laboratory of stereotactic methods

Russian Federation, 197376, St. Petersburg, Academician Pavlov Str., 9

Elena V. Kryukova

N.P. Beсhtereva Institute of Human Brain of the Russian Academy of Sciences

Email: eldementyeva@gmail.com
ORCID iD: 0000-0002-5395-9931

Cand. Sci. (Med.), neurologist, Multiply sclerosis center

Russian Federation, 197376, St. Petersburg, Academician Pavlov Str., 9

Andrey M. Petrov

N.P. Beсhtereva Institute of Human Brain of the Russian Academy of Sciences

Email: apetrov@ihb.spb.ru
ORCID iD: 0000-0001-9648-5492

Cand. Sci. (Med.), leading expert, Laboratory of neuroimaging

Russian Federation, 197376, St. Petersburg, Academician Pavlov Str., 9

Tatyana N. Trofimova

N.P. Beсhtereva Institute of Human Brain of the Russian Academy of Sciences

Email: TTrofimova@sogaz-clinic.ru
ORCID iD: 0000-0003-4871-2341

D. Sci. (Med.), Prof., leading researcher, Laboratory of neuroimaging

Russian Federation, 197376, St. Petersburg, Academician Pavlov Str., 9

Igor D. Stolyarov

N.P. Beсhtereva Institute of Human Brain of the Russian Academy of Sciences

Author for correspondence.
Email: sid@ihb.spb.ru
ORCID iD: 0000-0001-8154-9107
https://ihb.spb.ru/staff/i-stolyarov

D. Sci. (Med.), Prof., Head, Multiply sclerosis center

Russian Federation, 197376, St. Petersburg, Academician Pavlov Str., 9

References

  1. Goodin D.S., Reder A.T., Bermel R.A. et al. Relapses in multiple sclerosis: Relationship to disability. Mult. Scler. Relat. Disord. 2016; 6: 10–20. doi: 10.1016/j.msard.2015.09.002
  2. Bevan C., Gelfand J.M. Therapeutic management of severe relapses in multiple sclerosis. Curr. Treat. Options Neurol. 2015; 17(4): 345. doi: 10.1007/s11940-015-0345-6
  3. Гусев Е.И., Бойко А.Н., Столяров И.Д. Рассеянный склероз. М.; 2015. 448 с. Gusev E.I., Boiko A.N., Stolyarov I.D. Multiple sclerosis. Moscow; 2015. 448 p. (In Russ.)
  4. Rovaris M., Comi G., Filippi M. The role of non-conventional MR techniques to study multiple sclerosis patients. J. Neurol. Sci. 2001; 186(Suppl 1): S3–S9. doi: 10.1016/s0022-510x(01)00485-3
  5. Sajja B.R., Wolinsky J.S., Narayana P.A. Proton magnetic resonance spectroscopy in multiple sclerosis. Neuroimaging Clin. N. Am. 2009; 19(1): 45–58. doi: 10.1016/j.nic.2008.08.002
  6. Tartaglia M.C., Narayanan S., De Stefano N. et al. Choline is increased in prelesional normal appearing white matter in multiple sclerosis. J. Neurol. 2002; 249(10): 1382–1390. doi: 10.1007/s00415-002-0846-6
  7. Chard D.T., Griffin C.M., McLean M.A. et al. Brain metabolite changes in cortical grey and normal-appearing white matter in clinically early relapsing- remitting multiple sclerosis. Brain. 2002; 125(Pt 10): 2342–2352. doi: 10.1093/brain/awf240
  8. Bogdan A.A., Kataeva G.V., Khomenko J.G. et al. Diagnostic value of short and long echo time in H-1-MRS for patients with multiple sclerosis. Appl. Magnet. Reson. 2017; 48: 707–714. doi: 10.1007/s00723-017-0900-2
  9. Lublin F.D., Reingold S.C., Cohen J.A. et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014; 83(3): 278–286. doi: 10.1212/WNL.0000000000000560
  10. Arnold D.L., Wolinsky J.S., Matthews P.M., Falini A. The use of magnetic resonance spectroscopy in the evaluation of the natural history of multiple sclerosis. J. Neurol. Neurosurg. Psychiatry. 1998; 64(Suppl 1): S94–S101.
  11. Sarchielli P., Presciutti O., Pelliccioli G.P. et al. Absolute quantification of brain metabolites by proton magnetic resonance spectroscopy in normal-appearing white matter of multiple sclerosis patients. Brain. 1999; 122 (Pt 3): 513–521. doi: 10.1093/brain/122.3.513
  12. Llufriu S., Kornak J., Ratiney H. et al. Magnetic resonance spectroscopy markers of disease progression in multiple sclerosis. JAMA Neurol. 2014; 71(7): 840–847. doi: 10.1001/jamaneurol.2014.895
  13. Narayana P.A., Doyle T.J., Lai D., Wolinsky J.S. Serial proton magnetic resonance spectroscopic imaging, contrast-enhanced magnetic resonance imaging, and quantitative lesion volumetry in multiple sclerosis. Ann. Neurol. 1998; 43(1): 56–71. doi: 10.1002/ana.410430112
  14. De Stefano N., Matthews P.M., Antel J.P. et al. Chemical pathology of acute demyelinating lesions and its correlation with disability. Ann. Neurol. 1995; 38(6): 901–909. doi: 10.1002/ana.410380610
  15. Schocke M.F., Berger T., Felber S.R. et al. Serial contrast-enhanced magnetic resonance imaging and spectroscopic imaging of acute multiple sclerosis lesions under high-dose methylprednisolone therapy. Neuroimage. 2003; 20(2): 1253–1263. doi: 10.1016/S1053-8119(03)00409-9
  16. Brenner R.E., Munro P.M., Williams S.C. et al. The proton NMR spectrum in acute EAE: the significance of the change in the Cho:Cr ratio. Magn. Redon. Med. 1993; 29(6): 737–745. doi: 10.1002/mrm.1910290605
  17. Bitsch A., Bruhn H., Vougioukas V. et al. Inflammatory CNS demyelination: histopathologic correlation with in vivo quantitative proton MR spectroscopy. Am. J. Neuroradiol. 1999; 20(9): 1619–1627.
  18. Narayana P.A. Magnetic resonance spectroscopy in the monitoring of multiple sclerosis. J. Neuroimaging. 2005; 15(4 Suppl): 46S–57S. doi: 10.1177/1051228405284200
  19. De Stefano N., Filippi M., Miller D. et al. Guidelines for using proton MR spectroscopy in multicenter clinical MS studies. Neurology. 2007; 69(20): 1942–1952. doi: 10.1212/01.wnl.0000291557.62706.d3
  20. Degenhardt A., Ramagopalan S.V., Scalfari A., Ebers G.C. Clinical prognostic factors in multiple sclerosis: a natural history review. Nat. Rev. Neurol. 2009; 5(12): 672–682. doi: 10.1038/nrneurol.2009.178
  21. Arnold D.L., Matthews P.M. MRI in the diagnosis and management of multiple sclerosis. Neurology. 2002; 58(8 Suppl 4): S23–S31. doi: 10.1212/wnl.58.8_suppl_4.s23
  22. Filippi M., Agosta F. Imaging biomarkers in multiple sclerosis. J. Magn. Reson. Imaging. 2010; 31(4): 770–788.doi: 10.1002/jmri.22102
  23. Berkovich R. Treatment of acute relapses in multiple sclerosis. Neurotherapeutics. 2013; 10(1): 97–105. doi: 10.1007/s13311-012-0160-7
  24. Wattjes M.P., Harzheim M., Lutterbey G.G. et al. 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 highfield magnetic resonance spectroscopy. Am. J. Neuroradiol. 2007; 28(8): 1517–1522. doi: 10.3174/ajnr.A0594
  25. Khan O., Seraji-Bozorgzad N., Bao F. et al. The relationship between brain MR spectroscopy and disability in multiple sclerosis: 20-year data from the U.S. glatiramer acetate extension study. J. Neuroimaging. 2017; 27(1): 97–106. doi: 10.1111/jon.12358
  26. Fisniku L.K., Brex P.A., Altmann D.R. et al. Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain. 2008; 131(Pt 3): 808–817. doi: 10.1093/brain/awm329
  27. Rovira A., Auger C., Alonso J. Magnetic resonance monitoring of lesion evolution in multiple sclerosis. Ther. Adv. Neurol. Disord. 2013; 6(5): 298–310. doi: 10.1177/1756285613484079

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. NAA/Cho spectroscopic assessment before and after the IVGC treatment (median) in the cingulate gyri in the metabolic response group.

Download (43KB)
Indexing metadata
3. Fig. 2. Cho/Cr spectroscopic assessment before and after the IVGC treatment (median) in the cingulate gyri in the metabolic response group.

Download (44KB)
Indexing metadata
4. Fig. 3. The metabolic profile of the cingulate gyri grey matter in the RMS patients.

Download (54KB)
Indexing metadata
5. Fig. 4. Patient S. A — before the IVGC treatment: T2WI, multiple peripherally edematic demyelination foci in the frontal and parietal white matter; B — after the IVGC treatment: significant regression in several previously detected lesions.

Download (78KB)
Indexing metadata

Copyright (c) 2022 Shkilnyuk G.G., Bogdan A.A., Kryukova E.V., Petrov A.M., Trofimova T.N., Stolyarov I.D.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies