Proton magnetic resonance spectroscopy (1H-MRS) has been shown to be an important non-invasive tool to quantify neuronal loss or damage in the investigation of central nervous system (CNS) disorders. The purpose of this article is to discuss the clinical utility of 1H-MRS in determining CNS involvement in individuals with rheumatic autoimmune diseases.
Methods
This study is a systematic review of the literature, conducted during the month of November and December of 2019 of articles published in the last 16 years (2003-2019). The search for relevant references was done through the exploration of electronic databases (PubMed/Medline and Embase). We searched for studied including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), juvenile idiopathic arthritis, rheumatoid arthritis (RA), psoriasis, Sjögren's syndrome (pSS), vasculitis and Behçet. Only studies published after 2003 and with more than 20 patients were included.
Results
We included 26 articles. NAA/Cr ratios were significant lower and Cho/Cr ratios increased in several brain regions in SLE, SS, RA, SSc. Associations with disease activity, inflammatory markers, CNS manifestations and comorbidities was variable across studies and diseases.
Conclusion
The presence of neurometabolite abnormalities in patients without ouvert CNS manifestations, suggests that systemic inflammation, atherosclerosis or abnormal vascular reactivity may be associated with subclinical CNS manifestations. MRS may be a usefull non-invasive method for screening patients with risk for CNS manifestations.
AckermanJJGroveTHWongGGGadianDGRaddaGK.Mapping of metabolites in whole animals by 31P NMR using surface coils.Nature1980;
283: 167–170.
2.
BertholdoDWatcharakornACastilloM.Brain proton magnetic resonance spectroscopy: introduction and overview.Neuroimag Clin2013;
23: 359–380.
3.
FayedNOlmosSMoralesHModregoPJ.Physical basis of magnetic resonance spectroscopy and its application to central nervous system diseases. Am J Appl Sci2006;
3: 1836–1845.
4.
RamadaSLinAStanwellP.Glutamate and glutamine: a review of in vivo MRS in the human brain.NMR Biomed2013;
26: 1630–1646.
5.
AppenzellerSLiLMCostallatLTCendesF.Evidence of reversible axonal dysfunction in systemic lupus erythematosus: a proton MRS study.Brain2005;
128: 2933–2940.
6.
CagnoliPHarrisREFrechtlingD, et al.
Reduced insular glutamine and N-acetylaspartate in systemic lupus erythematosus: a single-voxel (1) H-MR spectroscopy study.Acad Radiol2013;
20: 1286–1296.
7.
MoatsRASchonkT.Evaluation of automated MR spectroscopy: application in Alzheimer disease. Am J Neuroradiol1995;
16: 1779–1782.
8.
BaslowMHGuilfoyleDN.Using proton magnetic resonance imaging and spectroscopy to understand brain activation. Brain Lang2007;
102: 153–164.
9.
PetrellaJRColemanREDoraiswamyPM.Neuroimaging and early diagnosis of Alzheimer disease: a look to the future.Radiology2003;
226: 315–336.
10.
RudkinTMArnoldDL.Proton magnetic resonance spectroscopy for the diagnosis and management of cerebral disorders.Arch Neurol1999;
56: 919–926.
11.
AxfordJSHoweFAHeronCGriffithsJR.Sensitivity of quantitative (1) H magnetic resonance spectroscopy of the brain in detecting early neuronal damage in systemic lupus erythematosus. Ann Rheum Dis2001;
60: 106–111.
LinAQShouJXLiXYMaLZhuXH.Metabolic changes in acute cerebral infarction: Findings from proton magnetic resonance spectroscopic imaging. Exp Ther Med2014;
7: 451–455.
14.
SundgrenPCJenningsJAttwoodJT, et al.
MRI and 2D-CSI MR spectroscopy of the brain in the evaluation of patients with acute onset of neuropsychiatric systemic lupus erythematosus. Neuroradiology2005;
47: 576–585.
15.
UrenjakJWilliamsSRGadianDGNobleM.Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci1993;
13: 981–989.
16.
HertzL.Intercellular metabolic compartmentation in the brain: past, present and future.Neurochem Int2004;
45: 285–296.
17.
ZhangYShenJ.Simultaneous quantification of glutamate and glutamine by J-modulated spectroscopy at 3 Tesla. Magn Reson Med2016;
76: 725–732.
18.
KozoraEBrownMSFilleyCM, et al.
Memory impairment associated with neurometabolic abnormalities of the hippocampus in patients with non-neuropsychiatric systemic lupus erythematosus.Lupus2011;
20: 598–606.
19.
PostalMCostallatLTAppenzellerS.Neuropsychiatric manifestations in systemic lupus erythematosus: epidemiology, pathophysiology, and management.CNS Drugs2011;
25: 721–736.
20.
AppenzellerSBonilhaLRioPAMin LiLCostallatLTCendesF.Longitudinal analysis of gray and white matter loss in patients with systemic lupus erythematosus.NeuroImage2007;
34: 694–701.
21.
ZimnyASzmyrka-KaczmarekMSzewczykP, et al.
In vivo evaluation of brain damage in the course of systemic lupus erythematosus using magnetic resonance spectroscopy, perfusion-weighted and diffusion-tensor imaging. Lupus2014;
23: 10–19.
22.
AmaralTNPeresFALapaATMarques-NetoJFAppenzellerS.Neurologic involvement in scleroderma: a systematic review.Sem Arthritis Rheum2013;
43: 335–347.
23.
MedanaIMEsiriMM.Axonal damage: a key predictor of outcome in human CNS diseases.Brain2003;
126: 515–530.
24.
BreretonPKitchenhamBABudgenDTurnerMKhalilM.Lessons from applying the systematic literature review process within the software engi- neering domain. J Syst Softw2007;
80: 571–583.
25.
MoherDShamseerLClarkeM, et al.
Preferred reporting items for systematic review and meta-analysis protocols (prisma-p) 2015 statement.Syst Rev2015; 4: 1--9.
26.
Covidence: Accelerate your systematic review 2019, www.covidence.org/ (2019, accessed 1 December 2019).
27.
AppenzellerSLiLMCostallatLTCendesF.Neurometabolic changes in normal white matter may predict appearance of hyperintense lesions in systemic lupus erythematosus.Lupus2007;
16: 963–971.
28.
BosmaGTSteensSCAPetropoulosH, et al.
Multisequence magnetic resonance imaging study of neuropsychiatric systemic lupus erythematosus.Arthritis Rheum2004;
50: 3195–3202.
29.
EmmerBJSteup‐BeekmanGMSteensSCAHuizingaTWJvan BuchemMAvan Der GrondJ.Correlation of magnetization transfer ratio histogram parameters with neuropsychiatric systemic lupus erythematosus criteria and proton magnetic resonance spectroscopy: association of magnetization transfer ratio peak height with neuronal and cognitive dysfunction. Arthritis Rheum2008;
58: 1451–1457.
30.
ErcanEMagro-ChecaCValabregueR, et al.
Glial and axonal changes in systemic lupus erythematosus measured with diffusion of intracellular metabolites.Brain2016;
139: 1447–1457.
31.
FilleyCMKozoraEBrownMS, et al.
White matter microstructure and cognition in non-neuropsychiatric systemic lupus erythematosus. Cogn Behav Neurol2009;
22: 38–44.
32.
KozoraEArciniegasDBDugganEWestSBrownMFilleyCM.White matter abnormalities and working memory impairment in systemic lupus erythematosus. Cogn Behav Neurol2013;
26: 63.
33.
KozoraEFilleyCMZhangL, et al.
Immune function and brain abnormalities in patients with systemic lupus erythematosus without overt neuropsychiatric manifestations.Lupus2012;
21: 402–411.
34.
LaptevaLNowakMYarboroCH, et al.
Anti–N‐methyl‐D‐aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus. Arthritis Rheum2006;
54: 2505–2514.
35.
ZhangZWangYShenZ, et al.
The neurochemical and microstructural changes in the brain of systemic lupus erythematosus patients: a multimodal MRI study. Sci Rep2016;
6: 19026.
36.
ZimnyASzmyrka-KaczmarekMSzewczykP, et al.
In vivo evaluation of brain damage in the course of systemic lupus erythematosus using magnetic resonance spectroscopy, perfusion-weighted and diffusion-tensor imaging. Lupus2014;
23: 10–19.
37.
MortillaMErminiMNistriMPozzoGDFalciniF.Brain study using magnetic resonance imaging and proton MR spectroscopy in pediatric onset systemic lupus erythematosus. Clin Exp Rheumatol2013;
21: 129–135.
38.
SriramSKavithaMMTamilselvamTNMaryDTRajeswariM.Role of proton magnetic resonance spectroscopy in determining the neurometabolism of neuropsychiatric systemic lupus erythematosus (NPSLE). Indian J Rheumatol2014;
9: 35.
39.
WangPIHarrisREChenevertTLMcCuneWJSundgrenPC.Multi-voxel proton magnetic resonance spectroscopy changes in neuropsychiatric lupus patients. SA J Radiol2016;
20: 1.
40.
ChanLLWanCMRumpelH, et al.
Do metabolic changes affect the hippocampus in SLE?Proceedings of 45th SMCM 2011; 40: 18.
41.
PerryJHarrisREBeyerG, et al.
NAA and glutamate as neuronal biomarkers in systemic lupus erythematosus (SLE) and neuropsychiatric systemic lupus erythematosus (NSPLE) patients. A single voxel study. Eur Soc Neuroradiol Annu Meeting2009;
51: 46.
HaiderHMZakaryaSAbu-HegazyM.White matter microstructure and cognitive dysfunction in systemic lupus patients. Egypt J Neurol Psychiatry Neurosurg2012;
49: 199–206.
44.
WanCMChanLLRumpelH, et al.
Metabolic changes on MR spectroscopy of the hippocampus in SLE neuroradiology journal. Clin Res2010;
23: 186–187.
45.
BertinottiLMortillaMConfortiML, et al. Proton magnetic resonance spectroscopy reveals central neuroaxonal impairment in systemic sclerosis. J Rheumatol2006;
33: 546–551.
46.
PereiraDFreschiMFrittoliR, et al.
Axonal dysfunction in cerebral white matter in systemic sclerosis: a proton magnetic resonance spectroscopic imaging (1H-MRSI) study. Ann Rheum Dis2019;
78: 442.
47.
MorrealeMMarchionePGiacominiP, et al.
Neurological involvement in primary Sjögren syndrome: a focus on central nervous system.PLoS One2014;
9: e84605.
48.
BaysalTOzisikHIKarlidagR, et al.
Proton MRS in Behçet’s disease with and without neurological findings.Neuroradiology2003;
45: 860–864.
49.
EmmerBJvan der BijlAEHuizingaTW, et al.
Brain involvement in rheumatoid arthritis: a magnetic resonance spectroscopy study.Arthritis Rheum2009;
60: 3190–3195.
50.
de AmorimJCFrittoliRBPereiraD, et al.
Epidemiology, characterization and diagnosis of neuropsychiatric events in systemic lupus erythematosus. Expert Rev Clin Immunol2019;
15: 407–416.
51.
VoAVolpeBTTangCC, et al.
Regional brain metabolism in a murine systemic lupus erythematosus model.J Cereb Blood Flow Metab2014;
34: 1315–1320.
52.
van der GraafM.In vivo magnetic resonance spectroscopy: basic methodology and clinical applications.Eur Biophy J2010;
39: 527–540.
