1H-NMR-based metabolomic analysis of cerebrospinal fluid from adult bilateral moyamoya disease: comparison with unilateral moyamoya disease and atherosclerotic stenosis.
Although metabolomics has been increasingly used to observe metabolic pattern and disease-specific metabolic markers, metabolite profiling for moyamoya disease (MMD) has not yet been done in adults. This study investigated cerebrospinal fluid (CSF) metabolites specific to bilateral MMD (B-MMD) and compared them to those of unilateral MMD (U-MMD) or atherosclerotic stenosis with hydrogen-1 nuclear magnetic resonance spectroscopy to identify metabolic biomarkers associated with MMD in adults.CSF samples of B-MMD (n = 29), U-MMD (n = 11), and atherosclerotic cerebrovascular disease (ACVD) (n = 8) were recruited. Principal component analysis, partial least square discriminant analysis, and orthogonal projections to latent structure discriminant analysis (OPLS-DA) were done for the comparisons. Diagnostic performance was acquired by prediction of 1 left-out sample from the distinction model constructed with the rest of the samples.B-MMD showed an increase in glutamine (P < 0.001) and taurine (P = 0.004), and a decrease in glucose (P < 0.001), citrate (P = 0.002), and myo-inositol (P = 0.006) than those in ACVD. U-MMD showed a higher level of glutamine (P = 0.005) and taurine (P = 0.034), and a lower level of glutamate (P < 0.004) than those in ACVD. No difference at the metabolite level was observed between B-MMD and U-MMD. Cross-validation with the OPLS-DA model showed a high accuracy for the prediction of MMD.The results of the study suggest that a metabolomics approach may be helpful in confirming MMD and providing a better understanding of MMD pathogenesis. Elevated glutamine in the CSF may be associated with MMD pathogenesis, which was different from ACVD.
From the Department of Neurosurgery (JPJ), Hallym University College of Medicine, Chuncheon; College of Pharmacy (TY, XJ, SP), Seoul National University; and Department of Neurosurgery (JEK, W-SC, Y-JS, JSB, H-SK, CWO), Seoul National University College of Medicine, Seoul, Korea.
Jin Pyeong
JP
Jeon
Taeho
T
Yun
Xing
X
Jin
Won-Sang
WS
Cho
Young-Je
YJ
Son
Jae Seung
JS
Bang
Hyun-Seung
HS
Kang
Chang Wan
CW
Oh
Jeong Eun
JE
Kim
Sunghyouk
S
Park
D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid; D019343:Citric Acid / Q000134:cerebrospinal fluid; D005260:Female; D005947:Glucose / Q000134:cerebrospinal fluid; D018698:Glutamic Acid / Q000134:cerebrospinal fluid; D005973:Glutamine / Q000134:cerebrospinal fluid; D006801:Humans; D007294:Inositol / Q000134:cerebrospinal fluid; D002537:Intracranial Arteriosclerosis / Q000134:cerebrospinal fluid; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D009072:Moyamoya Disease / Q000134:cerebrospinal fluid*; D011446:Prospective Studies; D013654:Taurine / Q000134:cerebrospinal fluid
D015415:Biomarkers; D005973:Glutamine; D013654:Taurine; D019343:Citric Acid; D018698:Glutamic Acid; D007294:Inositol; D005947:Glucose