NAA is a Marker of Disability in Secondary-Progressive MS: A Proton MR Spectroscopic Imaging Study

References

1. 1.↵
   1. Ontaneda D,
   2. Thompson AJ,
   3. Fox RJ, et al

   . Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function. Lancet 2017;389:1357–66 doi:10.1016/S0140-6736(16)31320-4 pmid:27889191

   CrossRefPubMed
2. 2.↵
   1. Mahad DH,
   2. Trapp BD,
   3. Lassmann H

   . Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol 2015;14:183–93 doi:10.1016/S1474-4422(14)70256-X pmid:25772897

   CrossRefPubMed
3. 3.↵
   1. Paling D,
   2. Golay X,
   3. Wheeler-Kingshott C, et al

   . Energy failure in multiple sclerosis and its investigation using MR techniques. J Neurol 2011;258:2113–27 doi:10.1007/s00415-011-6117-7 pmid:21660561

   CrossRefPubMedWeb of Science
4. 4.↵
   1. Macrez R,
   2. Stys PK,
   3. Vivien D, et al

   . Mechanisms of glutamate toxicity in multiple sclerosis: biomarker and therapeutic opportunities. Lancet Neurol 2016;15:1089–102 doi:10.1016/S1474-4422(16)30165-X pmid:27571160

   CrossRefPubMed
5. 5.↵
   1. Brown JW,
   2. Chard DT

   . The role of MRI in the evaluation of secondary progressive multiple sclerosis. Expert Rev Neurother 2016;16:157–71 doi:10.1586/14737175.2016.1134323 pmid:26692498

   CrossRefPubMed
6. 6.↵
   1. Ciccarelli O,
   2. Toosy AT,
   3. De Stefano N, et al

   . Assessing neuronal metabolism in vivo by modeling imaging measures. J Neurosci 2010;30:15030–33 doi:10.1523/JNEUROSCI.3330-10.2010 pmid:21068308

   Abstract/FREE Full Text
7. 7.↵
   1. Rovira À,
   2. Alonso J

   . 1H magnetic resonance spectroscopy in multiple sclerosis and related disorders. Neuroimaging Clin N Am 2013;23:459–74 doi:10.1016/j.nic.2013.03.005 pmid:23928200

   CrossRefPubMedWeb of Science
8. 8.↵
   1. Bitsch A,
   2. Bruhn H,
   3. Vougioukas V, et al

   . Inflammatory CNS demyelination: histopathologic correlation with in vivo quantitative proton MR spectroscopy. AJNR Am J Neuroradiol 1999;20:1619–27 pmid:10543631

   Abstract/FREE Full Text
9. 9.↵
   1. Swanberg KM,
   2. Landheer K,
   3. Pitt D, et al

   . Quantifying the metabolic signature of multiple sclerosis by in vivo proton magnetic resonance spectroscopy: current challenges and future outlook in the translation from proton signal to diagnostic biomarker. Front Neurol 2019;10:1173 doi:10.3389/fneur.2019.01173 pmid:31803127

   CrossRefPubMed
10. 10.↵
    1. Narayana PA,
    2. Wolinsky JS,
    3. Rao SB, et al

    ; PROMiSe Trial MRSI Group. Multicentre proton magnetic resonance spectroscopy imaging of primary progressive multiple sclerosis. Mult Scler 2004;10(Suppl 1):S73–78 doi:10.1177/135245850401000113 pmid:15218814

    CrossRefPubMedWeb of Science
11. 11.↵
    1. Vrenken H,
    2. Barkhof F,
    3. Uitdehaag BMJ, et al

    . MR spectroscopic evidence for glial increase but not for neuro-axonal damage in MS normal-appearing white matter. Magn Reson Med 2005;53:256–66 doi:10.1002/mrm.20366 pmid:15678547

    CrossRefPubMedWeb of Science
12. 12.↵
    1. Rovaris M,
    2. Gallo A,
    3. Falini A, et al

    . Axonal injury and overall tissue loss are not related in primary progressive multiple sclerosis. Arch Neurol 2005;62:898–902 doi:10.1001/archneur.62.6.898 pmid:15956160

    CrossRefPubMedWeb of Science
13. 13.↵
    1. Geurts JJG,
    2. Reuling IEW,
    3. Vrenken H, et al

    . MR spectroscopic evidence for thalamic and hippocampal, but not cortical, damage in multiple sclerosis. Magn Reson Med 2006;55:478–83 doi:10.1002/mrm.20792 pmid:16463353

    CrossRefPubMedWeb of Science
14. 14.↵
    1. Sastre-Garriga J,
    2. Ingle GT,
    3. Chard DT, et al

    . Metabolite changes in normal-appearing gray and white matter are linked with disability in early primary progressive multiple sclerosis. Arch Neurol 2005;62:569 doi:10.1001/archneur.62.4.569 pmid:15824254

    CrossRefPubMedWeb of Science
15. 15.↵
    1. Hannoun S,
    2. Bagory M,
    3. Durand-Dubief F, et al

    . Correlation of diffusion and metabolic alterations in different clinical forms of multiple sclerosis. PLoS One 2012;7:e32525 doi:10.1371/journal.pone.0032525 pmid:22479330

    CrossRefPubMed
16. 16.↵
    1. Obert D,
    2. Helms G,
    3. Sättler MB, et al

    . Brain metabolite changes in patients with relapsing-remitting and secondary progressive multiple sclerosis: a two-year follow-up study. PLoS One 2016;11:e0162583 doi:10.1371/journal.pone.0162583 pmid:27636543

    CrossRefPubMed
17. 17.↵
    1. Foong J,
    2. Rozewicz L,
    3. Davie CA, et al

    . Correlates of executive function in multiple sclerosis. J Neuropsychiatry Clin Neurosci 1999;11:45–50 doi:10.1176/jnp.11.1.45 pmid:9990555

    CrossRefPubMedWeb of Science
18. 18.↵
    1. Cox D,
    2. Pelletier D,
    3. Genain C, et al

    . The unique impact of changes in normal appearing brain tissue on cognitive dysfunction in secondary progressive multiple sclerosis patients. Mult Scler 2004;10:626–29 doi:10.1191/1352458504ms1095oa pmid:15584486

    CrossRefPubMedWeb of Science
19. 19.↵
    1. Connick P,
    2. Angelis FD,
    3. Parker RA, et al

    ; UK Multiple Sclerosis Society Clinical Trials Network. Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART): a multiarm phase IIb randomised, double-blind, placebo-controlled clinical trial comparing the efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis. BMJ Open 2018;8:e021944 doi:10.1136/bmjopen-2018-021944 pmid:30166303

    Abstract/FREE Full Text
20. 20.↵
    1. Chataway J,
    2. De Angelis F,
    3. Connick P, et al

    ; MS-SMART Investigators. Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART): a phase 2b, multiarm, double-blind, randomised placebo-controlled trial. Lancet Neurol 2020;19:214–25 doi:10.1016/S1474-4422(19)30485-5 pmid:31981516

    CrossRefPubMed
21. 21.↵
    1. Kurtzke JF

    . Rating neurologic impairment in multiple sclerosis: an Expanded Disability Status Scale (EDSS). Neurology 1983;33:1444–52 doi:10.1212/wnl.33.11.1444 pmid:6685237

    Abstract/FREE Full Text
22. 22.↵
    1. Cutter GR,
    2. Baier ML,
    3. Rudick RA, et al

    . Development of a multiple sclerosis functional composite as a clinical trial outcome measure. Brain 1999;122:871–82 doi:10.1093/brain/122.5.871 pmid:10355672

    CrossRefPubMedWeb of Science
23. 23.↵
    1. Benedict RH,
    2. DeLuca J,
    3. Phillips G, et al

    ; Multiple Sclerosis Outcome Assessments Consortium. Validity of the Symbol Digit Modalities Test as a cognition performance outcome measure for multiple sclerosis. Mult Scler 2017;23:721–33 doi:10.1177/1352458517690821 pmid:28206827

    CrossRefPubMed
24. 24.↵
    1. Brink HF,
    2. Buschmann MD,
    3. Rosen BR

    . NMR chemical shift imaging. Comput Med Imaging Graph 1989;13:93–104 doi:10.1016/0895-6111(89)90081-5 pmid:2538222

    CrossRefPubMed
25. 25.↵
    1. Shen J,
    2. Rothman DL,
    3. Hetherington HP, et al

    . Linear projection method for automatic slice shimming. Magn Reson Med 1999;42:1082–88 doi:10.1002/(SICI)1522-2594(199912)42:6<1082::AID-MRM12>3.0.CO;2-G pmid:10571929

    CrossRefPubMed
26. 26.↵
    1. Modat M,
    2. Ridgway GR,
    3. Taylor ZA, et al

    . Fast free-form deformation using graphics processing units. Comput Methods Programs Biomed 2010;98:278–84 doi:10.1016/j.cmpb.2009.09.002 pmid:19818524

    CrossRefPubMedWeb of Science
27. 27.↵
    1. Prados F,
    2. Cardoso MJ,
    3. Kanber B, et al

    . A multi-time-point modality-agnostic patch-based method for lesion filling in multiple sclerosis. Neuroimage 2016;139:376–84 doi:10.1016/j.neuroimage.2016.06.053 pmid:27377222

    CrossRefPubMed
28. 28.↵
    1. Cardoso MJ,
    2. Modat M,
    3. Wolz R, et al

    . Geodesic Information Flows: spatially-variant graphs and their application to segmentation and fusion. IEEE Trans Med Imaging 2015;34:1976–88 doi:10.1109/TMI.2015.2418298 pmid:25879909

    CrossRefPubMed
29. 29.↵
    1. Smith SM,
    2. Zhang Y,
    3. Jenkinson M, et al

    . Accurate, robust, and automated longitudinal and cross-sectional brain change analysis. Neuroimage 2002;17:479–89 doi:10.1006/nimg.2002.1040 pmid:12482100

    CrossRefPubMedWeb of Science
30. 30.↵
    LCModel & LCMgui User’s Manual. http://s-provencher.com/pub/LCModel/manual/manual.pdf. Accessed 6th October, 2020
31. 31.↵
    1. Ernst T,
    2. Kreis R,
    3. Ross BD

    . Absolute quantitation of water and metabolites in the human brain, I: compartments and water. J Magn Reson Ser B 1993;102:1–8 doi:10.1006/jmrb.1993.1055

    CrossRefWeb of Science
32. 32.↵
    1. Solana E,
    2. Martinez-Heras E,
    3. Martinez-Lapiscina EH, et al

    . Magnetic resonance markers of tissue damage related to connectivity disruption in multiple sclerosis. NeuroImage Clin 2018;20:161–68 doi:10.1016/j.nicl.2018.07.012 pmid:30094165

    CrossRefPubMed
33. 33.↵
    R Core Team. R: A language and environment for statistical computing. 2017. https://cran.r-project.org/doc/manuals/r-release/fullrefman.pdf. Accessed March 12, 2020
34. 34.↵
    1. Patel CJ,
    2. Ioannidis JP

    . Placing epidemiological results in the context of multiplicity and typical correlations of exposures. J Epidemiol Community Health 2014;68:1096–100 doi:10.1136/jech-2014-204195 pmid:24923805

    Abstract/FREE Full Text
35. 35.↵
    1. Giovannoni G,
    2. Cutter G,
    3. Pia-Sormani M, et al

    . Is multiple sclerosis a length-dependent central axonopathy? The case for therapeutic lag and the asynchronous progressive MS hypotheses. Mult Scler Relat Disord 2017;12:70–78 doi:10.1016/j.msard.2017.01.007 pmid:28283111

    CrossRefPubMed
36. 36.↵
    1. De Stefano N,
    2. Narayanan S,
    3. Francis GS, et al

    . Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability. Arch Neurol 2001;58:65–70 doi:10.1001/archneur.58.1.65 pmid:29968175

    CrossRefPubMedWeb of Science
37. 37.↵
    1. Penny S,
    2. Khaleeli Z,
    3. Cipolotti L, et al

    . Early imaging predicts later cognitive impairment in primary progressive multiple sclerosis. Neurology 2010;74:545–52 doi:10.1212/WNL.0b013e3181cff6a6 pmid:20157157

    Abstract/FREE Full Text
38. 38.↵
    1. Sonder JM,
    2. Burggraaff J,
    3. Knol DL, et al

    . Comparing long-term results of PASAT and SDMT scores in relation to neuropsychological testing in multiple sclerosis. Mult Scler 2014;20:481–88 doi:10.1177/1352458513501570 pmid:24019305

    CrossRefPubMed
39. 39.↵
    1. Forn C,
    2. Belenguer A,
    3. Belloch V, et al

    . Anatomical and functional differences between the paced auditory serial addition test and the symbol digit modalities test. J Clin Exp Neuropsychol 2011;33:42–50 doi:10.1080/13803395.2010.481620 pmid:20552497

    CrossRefPubMed
40. 40.↵
    1. López-Góngora M,
    2. Querol L,
    3. Escartín A

    . A one-year follow-up study of the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT) in relapsing-remitting multiple sclerosis: an appraisal of comparative longitudinal sensitivity. BMC Neurol 2015;15:40 doi:10.1186/s12883-015-0296-2 pmid:25886168

    CrossRefPubMed
41. 41.↵
    1. Miller BL

    . A review of chemical issues in1H NMR spectroscopy: N-acetyl-l-aspartate, creatine and choline. NMR Biomed 1991;4:47–52 doi:10.1002/nbm.1940040203 pmid:1650241

    CrossRefPubMedWeb of Science
42. 42.↵
    1. James RE,
    2. Schalks R,
    3. Browne E, et al

    . Persistent elevation of intrathecal pro-inflammatory cytokines leads to multiple sclerosis-like cortical demyelination and neurodegeneration. Acta Neuropathol Commun 2020;8:66 doi:10.1186/s40478-020-00938-1 pmid:32398070

    CrossRefPubMed
43. 43.↵
    1. Magliozzi R,
    2. Howell O,
    3. Vora A, et al

    . Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain 2007;130:1089–104 doi:10.1093/brain/awm038 pmid:17438020

    CrossRefPubMedWeb of Science
44. 44.↵
    1. MacMillan E,
    2. Tam R,
    3. Zhao Y, et al

    . Progressive multiple sclerosis exhibits decreasing glutamate and glutamine over two years. Mult Scler J 2016;22:112–16 doi:10.1177/1352458515586086 pmid:26014604

    CrossRefPubMed
45. 45.↵
    1. Caramanos Z,
    2. DiMaio S,
    3. Narayanan S, et al

    . 1H-MRSI evidence for cortical gray matter pathology that is independent of cerebral white matter lesion load in patients with secondary progressive multiple sclerosis. J Neurol Sci 2009;282:72–79 doi:10.1016/j.jns.2009.01.015 pmid:19232641

    CrossRefPubMed
46. 46.↵
    1. Sarchielli P,
    2. Presciutti O,
    3. Tarducci R, et al

    . Localized (1)H magnetic resonance spectroscopy in mainly cortical gray matter of patients with multiple sclerosis. J Neurol 2002;249:902–10 doi:10.1007/s00415-002-0758-5 pmid:12140676

    CrossRefPubMedWeb of Science
47. 47.↵
    1. Adalsteinsson E,
    2. Langer-Gould A,
    3. Homer RJ, et al

    . Gray matter N-acetyl aspartate deficits in secondary progressive but not relapsing-remitting multiple sclerosis. AJNR Am J Neuroradiol 2003;24:41–45 pmid:14625214

    PubMed
48. 48.↵
    1. Motl RW,
    2. Cohen JA,
    3. Benedict R, et al

    ; Multiple Sclerosis Outcome Assessments Consortium. Validity of the timed 25-foot walk as an ambulatory performance outcome measure for multiple sclerosis. Mult Scler 2017;23:704–10 doi:10.1177/1352458517690823 pmid:28206828

    CrossRefPubMed
49. 49.↵
    1. Azevedo CJ,
    2. Kornak J,
    3. Chu P, et al

    . In vivo evidence of glutamate toxicity in multiple sclerosis. Ann Neurol 2014;76:269–78 doi:10.1002/ana.24202 pmid:25043416

    CrossRefPubMed