TABLE 1.
Key data points extracted from the refined studies.
| Author | Title | Year of publication | Sample size | Study design | Type of control | Sample analysis technique |
| Aasly et al. | Cerebrospinal fluid lactate and glutamine are reduced in multiple sclerosis | 1997 | 10 patients with chronic, progressive MS • 10 RRMS • 14 HC |
Cross-sectional | HC | MRS |
| Aeinehband et al. | Cerebrospinal fluid kynurenine in multiple sclerosis; relation to disease course and neurocognitive symptoms | 2016 | Cohort 1 • 38 MS patients • 20 patients with “other neurological disorder” (OND) • 13 patients with other, inflammatory neurological disorders (iOND) • Cohort 2 • 48 RRMS |
Cross-sectional | OND | LC-MS |
| Augutis et al. | Cerebrospinal fluid biomarkers of amyloid metabolism in multiple sclerosis | 2013 | 54 RRMS • 33 SPMS • 28 HC |
Cross-sectional and longitudinal | HC and baseline samples | Immunoassays, immunoprecipitation, mass spectrometry, LC-MS |
| Bystricka et al. | Methionine metabolism and multiple sclerosis | 2017 | 37 RRMS • 8 SPMS • 37 HC |
Cross-sectional | HC | ELISA assays, chromatography |
| Checa et al. | Hexosylceramides as intrathecal markers of worsening disability in multiple sclerosis | 2015 | 41 RRMS • 15 SPMS • 9 PPMS • 13 clinical isolated symptoms (CIS) • Two control groups: • 38 OND • 18 iOND. • 17 of the RRMS patients involved in the longitudinal study |
Cross-sectional and longitudinal (involving 17 RRMS patients with multiple measurements taken 4 years apart) | OND, iOND and baseline samples for the longitudinal study | ELISA assays, lLC-ESI-MS |
| Dickens et al. | A type 2 biomarker separates relapsing–remitting from secondary progressive multiple sclerosis | 2014 | Cohort A • 17 PPMS • 46 SPMS • 22 RRMS • 14 controls. • Cohort B • 10 SPMS • 6 RRMS • 7 controls • Cohort C • 10 SPMS • 5 RRMS • 7 controls |
Cross-sectional | “Control” | NMR spectroscopy |
| Cocco E | 1H-NMR analysis provides a metabolomic profile of patients with multiple sclerosis | 2015 | 61 RRMS • 12 patients with “progressive” MS • 88 HC |
Cross-sectional | HC | 1H-NMR spectroscopy |
| Gebregiworgis et al. | A Urinary Metabolic Signature for Multiple Sclerosis and Neuromyelitis Optica | 2016 | 8 RRMS • 9 neuromyelitis optica (NMO) • 7 HC |
Cross-sectional | HC and NMO | 1H-NMR spectroscopy |
| Hon et al. | Membrane saturated fatty acids and disease progression in Multiple Sclerosis patients | 2009 | 28 RRMS • 1 PPMS • 2 SPMS • 30 HC |
Cross-sectional | HC | GC |
| Hon et al. | Plasma non-esterified fatty acids in patients with multiple sclerosis | 2011 | 31 MS • 30 HC |
Cross-sectional | HC | GC |
| Hon et al. | Erythrocyte membrane fatty acids in patients with multiple sclerosis | 2009 | 28 RRMS • 1 PPMS • 2 SPMS • 30 HC |
Cross-sectional | HC | GC |
| Kim et al. | Metabolomic profiling of CSF in multiple sclerosis and neuromyelitis optica spectrum disorder by nuclear magnetic resonance | 2017 | 50 MS • 57 patients with NMO • 17 HC |
Cross-sectional | HC | NMR |
| Lazzarino et al. | Cerebrospinal fluid ATP metabolites in multiple sclerosis | 2010 | 21 MS | Prospective, longitudinal study where previous samples had been taken 3 years apart | Baseline levels and data from controls of a previous study | HPLC and ELISA |
| Lim et al. | Kynurenine pathway metabolomics predicts and provides mechanistic insight into multiple sclerosis progression | 2017 | Cohort 1 • 50 RRMS • 20 SPMS • 17 PPMS • 49 HC • Cohort 2 • 44 RRMS • 15 SPMS • Cohort 3 • 10 RRMS • 20 SPMS • 6 HC |
Cross-sectional and longitudinal | HC and baseline values | UHPLC and GC/MS |
| Lotsch et al. | Machine-Learned Data Structures of Lipid Marker Serum Concentrations in Multiple Sclerosis Patients Differ from Those in Healthy Subjects | 2017 | 102 MS • 301 HC |
Case–control | HC | LC-ESI-MS |
| Moussallieh et al. | Serum analysis by 1H Nuclear Magnetic Resonance spectroscopy: a new tool for distinguishing neuromyelitis optica from multiple sclerosis | 2014 | 47 RRMS • 44 NMO • 42 HC |
Cross-sectional | HC and NMO | 1H-NMR spectroscopy |
| Moyano et al. | Levels of plasma sulfatides C18: 0 and C24: 1 correlate with disease status in relapsing-remitting multiple sclerosis | 2013 | 14 RRMS • 14 HC |
Cross-sectional | HC | UHPLC-MS/MS |
| Navarro and Segura | Plasma lipids and their fatty acid composition in multiple sclerosis | 1988 | 61 MS (51 definite, 9 probable and 1 possible according to the classification by Rose et al.) • 61 HC |
Cross-sectional | HC | Thin-layer chromatography for lipids, GC for fatty acids and enzymatic methods |
| Park et al. | Disease Type- and Status-Specific Alteration of CSF Metabolome Coordinated with Clinical Parameters in Inflammatory Demyelinating Diseases of CNS | 2016 | 54 MS patients • 12 HC |
Cross-sectional | HC | GC/MS |
| Pieragostino et al. | An integrated metabolomics approach for the research of new cerebrospinal fluid biomarkers of multiple sclerosis | 2015 | 13 RRMS • 12 OND |
Cross-sectional | OND | targeted MALDI-TOF-MS and untargeted LC-MS/MS |
| Poddighe et al. | Metabolomic analysis identifies altered metabolic pathways in Multiple Sclerosis | 2017 | 28 RRMS • 4 progress MS • 33 HC |
Cross-sectional | HC | GC/MS |
| Regenold et al. | Cerebrospinal fluid evidence of increased extra-mitochondrial glucose metabolism implicates mitochondrial dysfunction in multiple sclerosis disease progression | 2008 | 22 remitted RRMS • 9 relapsed RRMS • 37 stationary SPMS • 17 relapsed SPMS • 18 HC |
Cross-sectional, pilot | HC | GC/MS |
| Reinke et al. | Metabolomic profiling in multiple sclerosis: insights into biomarkers and pathogene | 2014 | 11 RRMS • 3 SPMS • 1 CIS • 17 non-MS controls |
Cross-sectional | Non-MS controls | 1H-NMR spectroscopy |
| Salemi et al. | Blood lipids, homocysteine, stress factors, and vitamins in clinically stable multiple sclerosis patients | 2010 | 28 RRMS • 12 SPMS • 80 HC (2 controls:1 MS case |
Cross-sectional | HC | Enzymatic colorimetric tests HPLC and fluorimetry competitive magnetic separation |
| Sinclair et al. | NMR-based metabolomic analysis of cerebrospinal fluid and serum in neurological diseases—a diagnostic tool? | 2010 | Cohort 1 • 12 CSF and 11 serum samples from people with MS, • 25 CSF and 17 serum samples from people with IIH, • 9 CSF and 9 serum samples from people with CVD and • 41 CSF samples and 35 serum samples from an “other group” of diseases. • Cohort 2 had • 8 IIH • 3 MS • 14 fitting the “other” group |
Cross-sectional | IIH and “other diseases” | 1H-NMR spectroscopy |
| Sternberg et al. | Plasma pentosidine: a potential biomarker in the management of multiple sclerosis | 2011 | 63 RRMS • 21 SPMS • 8 PPMS • 6 CIS • 43 HC |
Cross-sectional | HC | HPLC |
| Vegara et al. | A lipidomic approach to the study of human CD4T lymphocytes in multiple sclerosis | 2015 | 8 RRMS • 5 HC |
Cross-sectional | HC | GC and MALDI-TOF MS |