K. Strimbu and J. Tavel, What are biomarkers?, Current Opinion in HIV and AIDS, vol.5, issue.6, pp.463-66, 2010.
DOI : 10.1097/COH.0b013e32833ed177
URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078627

A. Van-gool, B. Henry, and E. Sprengers, From biomarker strategies to biomarker activities and back, Drug Discovery Today, vol.15, issue.3-4, pp.3-4121, 2010.
DOI : 10.1016/j.drudis.2009.11.004

M. Van-der-vaart and P. Pretorius, Is the role of circulating DNA as a biomarker of cancer being prematurely overrated?, Clinical Biochemistry, vol.43, issue.1-2, pp.26-36, 2010.
DOI : 10.1016/j.clinbiochem.2009.08.027

R. Bove and T. Chitnis, Sexual disparities in the incidence and course of MS, Clinical Immunology, vol.149, issue.2, pp.201-211, 2013.
DOI : 10.1016/j.clim.2013.03.005

E. Kingwell, J. Marriott, N. Jetté, T. Pringsheim, N. Makhani et al., Incidence and prevalence of multiple sclerosis in Europe: a systematic review, BMC Neurology, vol.22, issue.7, p.128, 2013.
DOI : 10.1159/000067107

M. Ron and E. Kahana, Multiple sclerosis: Geoepidemiology, genetics and the environment, Autoimmunity Reviews, Special Issue on The Environment Geoepidemiology and Autoimmune Diseases, vol.9, issue.5, pp.387-94, 2010.

M. Naegele and R. Martin, The good and the bad of neuroinflammation in multiple sclerosis, Handbook of ClinicalNeurology, vol.122, pp.59-87, 2014.
DOI : 10.1016/B978-0-444-52001-2.00003-0

L. Magy, La scl??rose en plaques, Actualit??s Pharmaceutiques Hospitali??res, vol.5, issue.19, pp.14-19, 2009.
DOI : 10.1016/S1769-7344(09)70013-7

A. Compston and A. Coles, Multiple sclerosis. The Lancet 372, pp.1502-1519, 2008.
URL : https://hal.archives-ouvertes.fr/hal-00996686

C. Pettinelli and D. Mcfarlin, Adoptive Transfer of Experimental Allergic Encephalomyelitis in SJL/J Mice after in Vitro Activation of Lymph Node Cells by Myelin Basic Protein

E. Huseby, D. Liggitt, T. Brabb, B. Schnabel, C. Ohlén et al., A Pathogenic Role for Myelin-Specific CD8(+) T Cells in a Model for Multiple Sclerosis The Neuroimmunology of Multiple Sclerosis: Possible Roles of T and B Lymphocytes in Immunopathogenesis, The Journal of Experimental Medicine. Journal of ClinicalImmunology, vol.19421, issue.52, pp.669-76, 2001.

D. Hafler, Multiple sclerosis, Journal of Clinical Investigation, vol.113, issue.6, pp.788-94, 2004.
DOI : 10.1172/JCI21357DS1

L. Balcer, Optic Neuritis, New England Journal of Medicine, vol.354, issue.12, pp.1273-80, 2006.
DOI : 10.1056/NEJMcp053247

J. Pearce, Lhermitte's sign., Journal of Neurology, Neurosurgery & Psychiatry, vol.57, issue.7, p.846, 2004.
DOI : 10.1136/jnnp.57.7.846-a

J. Selhorst and R. Saul, Uhthoff and His Symptom, Journal of Neuro-Ophthalmology: The Official Journal of the North American Neuro-Ophthalmology Society, vol.15, issue.2, pp.63-69, 1995.
DOI : 10.1097/00041327-199506000-00002

R. Milo and A. Miller, Revised diagnostic criteria of multiple sclerosis, Diagnostic criteria in Autoimmune diseases 9th International Congress on Autoimmunity, pp.4-5, 2014.
DOI : 10.1016/j.autrev.2014.01.012

J. Ouallet and B. Brochet, Aspects cliniques, physiopathologiques, et thérapeutiques de la sclérose en plaques

O. Gout, C. Bensa, and R. Assouad, Actualit??s th??rapeutiques de la scl??rose en plaques, La Revue de M??decine Interne, vol.31, issue.8, pp.575-80, 2010.
DOI : 10.1016/j.revmed.2009.08.008

J. Kurtzke, Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS), Neurology, vol.33, issue.11
DOI : 10.1212/WNL.33.11.1444

R. Pooley and . Aapm, Fundamental Physics of MR Imaging, RadioGraphics, vol.25, issue.4, pp.1087-1099, 2005.
DOI : 10.1148/rg.254055027

J. Nicholson, J. Lindon, and E. Holmes, 'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data, Xenobiotica, vol.13, issue.11, pp.291181-1189, 1999.
DOI : 10.1002/elps.1150191118

H. Davies, omics " technologies in food safety assessment.Food Control, SAFE FOODS -Towards a new risk analysis framework for food safety, pp.1601-1610, 2010.

D. Ellis, W. Dunn, J. Griffin, J. Allwood, and R. Goodacre, Metabolic fingerprinting as a diagnostic tool, Pharmacogenomics, vol.8, issue.9
DOI : 10.2217/14622416.8.9.1243

W. Dunn, R. Goodacre, L. Neyses, and M. Mamas, Integration of metabolomics in heart disease and diabetes research: current achievements and future outlook, Bioanalysis, vol.3, issue.19, pp.2205-2222, 2011.
DOI : 10.4155/bio.11.223

L. Blanchet, L. Buydens, and S. Wijmenga, NMR and pattern recognition methods in metabolomics: From data acquisition to biomarker discovery: A review, AnalyticaChimicaActa, vol.750, pp.82-97, 2012.

A. Meissner, A. Van-der-plas, V. Dasselaar, N. Deelder, A. Van-hilten et al., 1H-NMR metabolic profiling of cerebrospinal fluid in patients with complex regional pain syndrome???related dystonia, Pain, vol.155, issue.1, pp.190-196, 2014.
DOI : 10.1016/j.pain.2013.10.005

A. Sinclair, M. Viant, A. Ball, M. Burdon, E. Walker et al., NMR-based metabolomic analysis of cerebrospinal fluid and serum in neurological diseases - a diagnostic tool?, NMR in Biomedicine, vol.8, issue.3, pp.123-155, 2010.
DOI : 10.1002/nbm.1428

J. Schripsema, Application of NMR in plant metabolomics: techniques, problems and prospects, Phytochemical Analysis, vol.9, issue.1, pp.14-21, 2010.
DOI : 10.1002/pca.1185

E. Lenz and I. Wilson, Analytical Strategies in Metabonomics, Journal of Proteome Research, vol.6, issue.2, pp.443-458, 2007.
DOI : 10.1021/pr0605217

M. Dumas, E. Maibaum, C. Teague, H. Ueshima, B. Zhou et al., H NMR Spectroscopy Based Metabonomics for Large-Scale Epidemiological Research:?? the INTERMAP Study, Analytical Chemistry, vol.78, issue.7, pp.2199-208, 2006.
DOI : 10.1021/ac0517085

R. Verpoorte, Y. Choi, N. Mustafa, and H. Kim, Metabolomics: back to basics, Phytochemistry Reviews, vol.134, issue.3, pp.525-537, 2008.
DOI : 10.1007/s11101-008-9091-7

W. Reynolds and R. Enríquez, Choosing the Best Pulse Sequences, Acquisition Parameters, Postacquisition Processing Strategies, and Probes for Natural Product Structure Elucidation by NMR Spectroscopy, Journal of Natural Products, vol.65, issue.2, pp.221-244, 2002.
DOI : 10.1021/np010444o

H. Blasco, P. Corcia, C. Moreau, S. Veau, C. Fournier et al., 1H-NMR-Based Metabolomic Profiling of CSF in Early Amyotrophic Lateral Sclerosis, PLoS ONE, vol.64, issue.10, 2010.
DOI : 10.1371/journal.pone.0013223.t002

E. Holmes, T. Tsang, and S. Tabrizi, The application of NMR-based metabonomics in neurological disorders, NeuroRX, vol.157, issue.1, pp.358-72, 2006.
DOI : 10.1016/j.nurx.2006.05.004

S. Ringeissen, S. Connor, H. Thakkar, B. Sweatman, M. Hodson et al., Identification of potential non-invasive biomarkers of peroxisome proliferation in the rat, Toxicology, vol.194, issue.3, pp.246-247, 2004.

J. Cevallos-cevallos, J. Reyes-de-corcuera, E. Etxeberria, M. Danyluk, and G. Rodrick, Metabolomic analysis in food science: a review, Trends in Food Science & Technology, vol.20, issue.11-12, pp.11-12557, 2009.
DOI : 10.1016/j.tifs.2009.07.002

T. Ikeda, S. Kanaya, T. Yonetani, A. Kobayashi, and E. Fukusaki, Prediction of Japanese Green Tea Ranking by Fourier Transform Near-Infrared Reflectance Spectroscopy, Journal of Agricultural and Food Chemistry, vol.55, issue.24, pp.9908-9920, 2007.
DOI : 10.1021/jf0717642

N. Lutz, S. Maillet, F. Nicoli, P. Viout, and P. Cozzone, H NMR spectra of cerebrospinal fluid (CSF), FEBS Letters, vol.2, issue.2, pp.345-51, 1998.
DOI : 10.1016/S0014-5793(98)00262-2

A. Amantonico, P. Urban, and R. Zenobi, Analytical techniques for single-cell metabolomics: state of the art and trends, Analytical and Bioanalytical Chemistry, vol.19, issue.6, pp.2493-2504, 2010.
DOI : 10.1007/s00216-010-3850-1

A. Zhang, H. Sun, and X. Wang, Serum metabolomics as a novel diagnostic approach for disease: a systematic review, Analytical and Bioanalytical Chemistry, vol.400, issue.7198, pp.1239-1284, 2012.
DOI : 10.1007/s00216-012-6117-1

G. Hassan-smith, G. Wallace, M. Douglas, and A. Sinclair, The role of metabolomics in neurological disease, Journal of Neuroimmunology, vol.248, issue.1-2, pp.48-52, 2012.
DOI : 10.1016/j.jneuroim.2012.01.009

L. Beretta, Comparative Analysis of the Liver and Plasma Proteomes as a Novel and Powerful Strategy for

A. Fernie, R. Trethewey, A. Krotzky, and L. Willmitzer, Innovation: Metabolite profiling: from diagnostics to systems biology, Nature Reviews Molecular Cell Biology, vol.216, issue.9, pp.763-69, 2004.
DOI : 10.1021/ja0109388

R. Madsen, T. Lundstedt, and J. Trygg, Chemometrics in Metabolomics--a Review in HumanDiseaseDiagnosis

T. Dunckley, K. Coon, and D. Stephan, Discovery and development of biomarkers of neurological disease, Drug Discovery Today, vol.10, issue.5, pp.326-360, 2005.
DOI : 10.1016/S1359-6446(04)03353-7

F. Nicoli, J. Vion-dury, S. Confort-gouny, S. Maillet, J. Gastaut et al., Cerebrospinal fluid metabolic profiles in multiple sclerosis and degenerative dementias obtained by high resolution proton magnetic resonance spectroscopy, Académie des Sciences, vol.319, issue.7, pp.623-631, 1996.

M. Noga, A. Dane, S. Shi, A. Attali, H. Van-aken et al., Metabolomics of cerebrospinal fluid reveals changes in the central nervous system metabolism in a rat model of multiple sclerosis, Metabolomics, vol.58, issue.2
DOI : 10.1007/s11306-011-0306-3

J. Griffin and A. Nicholls, Metabolomics as a functional genomic tool for understanding lipid dysfunction in diabetes, obesity and related disorders, Pharmacogenomics, vol.7, issue.7, pp.1095-1107, 2006.
DOI : 10.2217/14622416.7.7.1095

J. Sébédio, E. Pujos-guillot, and M. Ferrara, Metabolomics in Evaluation of Glucose Disorders. Current Opinion in Clinical Nutrition and Metabolic Care, pp.412-430, 2009.

J. Feala, L. Coquin, G. Paternostro, and A. Mcculloch, IntegratingMetabolomics and PhenomicswithSystemsModels of CardiacHypoxia, Progress in Biophysics and MolecularBiology, vol.96, pp.1-3, 2008.

G. Lewis, A. Asnani, and R. Gerszten, Application of Metabolomics to CardiovascularBiomarker and

W. Claudino, A. Quattrone, L. Biganzoli, M. Pestrin, I. Bertini et al., Metabolomics: Available Results, Current Research Projects in Breast Cancer, and Future Applications, Journal of Clinical Oncology, vol.25, issue.19, pp.2840-2886, 2007.
DOI : 10.1200/JCO.2006.09.7550

J. Griffin and R. Kauppinen, A metabolomics perspective of human brain tumours, FEBS Journal, vol.33, issue.5, pp.1132-1171, 2007.
DOI : 10.1111/j.1742-4658.2007.05676.x

K. Jain, Cancer Biomarkers: Current Issues and Future Directions, Current Opinion in MolecularTherapeutics, vol.9, issue.6, pp.563-71, 2007.

M. Lauridsen, H. Bliddal, R. Christensen, B. Danneskiold-samsøe, R. Bennett et al., H NMR Spectroscopy-Based Interventional Metabolic Phenotyping: A Cohort Study of Rheumatoid Arthritis Patients, Journal of Proteome Research, vol.9, issue.9, pp.4545-53, 2010.
DOI : 10.1021/pr1002774

I. Bertini, A. Calabrò, D. Carli, V. Luchinat, C. Nepi et al., The Metabonomic Signature of CeliacDisease, Journal of ProteomeResearch, vol.8, issue.1, pp.170-77, 2009.

N. Lutz and P. Cozzone, Metabolic Profiling in Multiple Sclerosis and Other Disorders by Quantitative Analysis of Cerebrospinal Fluid Using Nuclear Magnetic Resonance Spectroscopy, Current Pharmaceutical Biotechnology, vol.12, issue.7, pp.1016-1025, 2011.
DOI : 10.2174/138920111795909122

O. Fliniaux, G. Gaillard, A. Lion, D. Cailleu, F. Mesnard et al., Influence of common preanalytical variations on the metabolic profile of serum samples in biobanks, Journal of Biomolecular NMR, vol.84, issue.2, pp.457-465, 2011.
DOI : 10.1007/s10858-011-9574-5

V. Avettand-fenoel, N. Celton, M. Coulhon, and D. Duchassaing, ??tude immunologique des prot??ines du liquide c??phalorachidien dans le contexte de scl??rose en plaques??: comparaison de techniques qualitatives et quantitatives, Immuno-analyse & Biologie Sp??cialis??e, vol.17, issue.4, pp.242-250, 2002.
DOI : 10.1016/S0923-2532(02)01200-0

A. Wuolikainen, M. Hedenström, T. Moritz, S. Marklund, H. Antti et al., Optimization of procedures for collecting and storing of CSF for studying the metabolome in ALS, Amyotrophic Lateral Sclerosis, vol.36, issue.4, pp.229-236, 2009.
DOI : 10.1016/0169-7439(87)80084-9

P. Goldsmith, K. Prasad, N. Ahmad, and J. Fisher, 1H NMR spectroscopic study of blood serum for the assessment of liver function in liver transplant patients, Journal of Gastrointestinal and Liver Diseases, vol.18, issue.4, pp.508-509, 2009.

H. Kim, Y. Choi, and R. Verpoorte, NMR-based metabolomic analysis of plants, Nature Protocols, vol.28, issue.3, pp.536-549, 2010.
DOI : 10.1016/j.chroma.2005.11.114

S. Meiboom and D. Gill, Modified Spin???Echo Method for Measuring Nuclear Relaxation Times, Review of Scientific Instruments, vol.29, issue.8, pp.688-691, 1958.
DOI : 10.1063/1.1716296

R. Mckay, How the 1D-NOESY suppresses solvent signal in metabonomics NMR spectroscopy: An examination of the pulse sequence components and evolution. Concepts in Magnetic Resonance, pp.197-220, 2011.

C. Ludwig and M. Viant, Two-dimensional J-resolved NMR spectroscopy: review of a key methodology in the metabolomics toolbox, Phytochemical Analysis, vol.51, issue.1, pp.22-32, 2010.
DOI : 10.1002/pca.1186

J. Mckenzie, J. Donarski, J. Wilson, and A. Charlton, Analysis of complex mixtures using high-resolution nuclear magnetic resonance spectroscopy and chemometrics, Progress in Nuclear Magnetic Resonance Spectroscopy, vol.59, issue.4, pp.336-359, 2011.
DOI : 10.1016/j.pnmrs.2011.04.003

T. Ebbels, J. Lindon, and M. Coen, Processing and Modeling of Nuclear Magnetic Resonance (NMR) Metabolic Profiles, Methods in Molecular Biology, vol.708, pp.365-388, 2011.
DOI : 10.1007/978-1-61737-985-7_21

A. Craig, O. Cloarec, E. Holmes, J. Nicholson, and J. Lindon, Scaling and Normalization Effects in NMR Spectroscopic Metabonomic Data Sets, Analytical Chemistry, vol.78, issue.7, pp.2262-2267, 2006.
DOI : 10.1021/ac0519312

D. Meyer, T. Sinnaeve, D. Van-gasse, B. Rietzschel, E. et al., Evaluation of standard and advanced preprocessing methods for the univariate analysis of blood serum 1H-NMR spectra, Analytical and Bioanalytical Chemistry, vol.4, issue.Suppl 7, pp.1781-1790, 2010.
DOI : 10.1007/s00216-010-4085-x

F. Savorani, G. Tomasi, and S. Engelsen, icoshift: A versatile tool for the rapid alignment of 1D NMR spectra, Journal of Magnetic Resonance, vol.202, issue.2
DOI : 10.1016/j.jmr.2009.11.012

M. Defernez and I. Colquhoun, Factors affecting the robustness of metabolite fingerprinting using 1H NMR spectra, Phytochemistry, vol.62, issue.6, pp.1009-1017, 2003.
DOI : 10.1016/S0031-9422(02)00704-5

J. Izquierdo-garcía, P. Villa, A. Kyriazis, L. Del-puerto-nevado, S. Pérez-rial et al., Descriptive review of current NMR-based metabolomic data analysis packages, Progress in Nuclear Magnetic Resonance Spectroscopy, vol.59, issue.3, pp.263-270, 2011.
DOI : 10.1016/j.pnmrs.2011.02.001

B. Beckwith-hall, J. Nicholson, A. Nicholls, P. Foxall, J. Lindon et al., Nuclear Magnetic Resonance Spectroscopic and Principal Components Analysis Investigations into Biochemical Effects of Three Model Hepatotoxins, Chemical Research in Toxicology, vol.11, issue.4, pp.260-272, 1998.
DOI : 10.1021/tx9700679

D. Wishart, M. Lewis, J. Morrissey, M. Flegel, K. Jeroncic et al., The human cerebrospinal fluid metabolome, Journal of Chromatography B, vol.871, issue.2, pp.164-173, 2008.
DOI : 10.1016/j.jchromb.2008.05.001

R. Mandal, A. Guo, K. Chaudhary, P. Liu, F. Yallou et al., Multi-platform characterization of the human cerebrospinal fluid metabolome: a comprehensive and quantitative update, Genome Medicine, vol.4, issue.4, p.38, 2012.
DOI : 10.1016/j.aca.2010.09.054

C. Polman, S. Reingold, G. Edan, M. Filippi, H. Hartung et al., Diagnostic criteria for multiple sclerosis: 2005 revisions to the ???McDonald Criteria???, Annals of Neurology, vol.6, issue.6, pp.840-846, 2005.
DOI : 10.1002/ana.20703

J. Nicholson and I. Wilson, High resolution proton magnetic resonance spectroscopy of biological fluids, Progress in Nuclear Magnetic Resonance Spectroscopy, vol.21, issue.4-5
DOI : 10.1016/0079-6565(89)80008-1

F. Dieterle, A. Ross, G. Schlotterbeck, and H. Senn, Probabilistic quotient normalization as robust method to account

I. Simone, F. Federico, M. Trojano, C. Tortorella, M. Liguori et al., High resolution proton MR spectroscopy of cerebrospinal fluid in MS patients. Comparison with biochemical changes in demyelinating plaques, Journal of the Neurological Sciences, vol.144, issue.1-2, pp.182-90, 1996.
DOI : 10.1016/S0022-510X(96)00224-9

I. Simone, C. Tortorella, F. Federico, M. Liguori, V. Lucivero et al., Axonal damage in multiple sclerosis plaques: a combined magnetic resonance imaging and 1H-magnetic resonance spectroscopy study, Journal of the Neurological Sciences, vol.182, issue.2
DOI : 10.1016/S0022-510X(00)00464-0

W. Regenold, P. Phatak, M. Makley, R. Stone, and M. Kling, Cerebrospinal fluid evidence of increased extramitochondrial glucose metabolism implicates mitochondrial dysfunction in multiple sclerosis disease progression, Journal of the Neurological Sciences, vol.275, pp.1-2106, 2008.

A. Smolinska, A. Attali, L. Blanchet, K. Ampt, T. Tuinstra et al., NMR and Pattern Recognition Can Distinguish Neuroinflammation and Peripheral Inflammation, Journal of Proteome Research, vol.10, issue.10, pp.4428-4438, 2011.
DOI : 10.1021/pr200203v

E. Frohman, M. Racke, and C. Raine, Multiple Sclerosis ??? The Plaque and Its Pathogenesis, New England Journal of Medicine, vol.354, issue.9, pp.942-955, 2006.
DOI : 10.1056/NEJMra052130

E. Hattingen, J. Magerkurth, U. Pilatus, A. Hübers, M. Wahl et al., Combined 1H and 31P spectroscopy provides new insights into the pathobiochemistry of brain damage in multiple sclerosis, NMR in Biomedicine, vol.20, issue.Suppl. 7, pp.536-546, 2011.
DOI : 10.1002/nbm.1621

J. Qian, J. Herrera, and P. Narayana, Proton Magnetic Resonance Spectroscopy and Histology, Journal of Neurotrauma, vol.27, issue.3, pp.599-610, 2010.
DOI : 10.1089/neu.2009.1145

P. Sarchielli, O. Presciutti, R. Tarducci, G. Gobbi, A. Alberti et al., Localized 1 H magnetic resonance spectroscopy in mainly cortical gray matter of patients with multiple sclerosis, Journal of Neurology, vol.249, issue.7, pp.902-910, 2002.
DOI : 10.1007/s00415-002-0758-5

A. Minagar and J. Alexander, Blood-brain barrier disruption in multiple sclerosis, Multiple Sclerosis, vol.9, issue.6, pp.540-549, 2003.
DOI : 10.1191/1352458503ms965oa