{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:55:11Z","timestamp":1781650511613,"version":"3.54.5"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Johann Wolfgang Goethe-Universit\u00e4t, Frankfurt am Main"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Metab Brain Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Glucose dysregulation in the CNS contributes to both inflammation and neurodegeneration in multiple sclerosis (MS). While glucose levels are routinely measured in peripheral blood, these levels do not necessarily reflect glucose levels in the central nervous system. We analysed data of\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200988 treatment-naive, newly-diagnosed MS patients. Primary outcomes included Expanded Disability Status Scale (EDSS), Symbol Digit Modalities Test (SDMT), Fatigue Scale for Motor and Cognitive Functions (FSMC) and Beck Depression Inventory-II (BDI-II) as well as cerebrospinal fluid (CSF) and serum glucose levels obtained at the time of initial diagnosis. Additionally, we analysed CSF lactate concentration. All blood and CSF samples were collected before the patients received any glucocorticoid treatment. Linear regression analysis revealed that after adjusting for age, sex, BMI and CSF\/serum albumin quotient, there was a significant association between CSF glucose levels and EDSS (\u00df=0.260,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.020), SDMT z scores (\u00df=-0.245,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.033) and BDI (\u00df=0.279,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.026). There were no associations with serum glucose levels (\u00df ranging from \u2212\u20090.067 to 0.170, all\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&gt;\u20090.05). CSF lactate concentration was not significantly associated with the clinical parameters (\u00df ranging from \u2212\u20090.048 to 0.184, all\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&gt;\u20090.05). Patients with higher CSF but not serum glucose concentrations exhibited higher physical disability, more cognitive impairment and worse depressive symptoms. Increased CSF glucose in MS might be a compensatory mechanism for CNS damage but also a landmark of mitochondrial dysfunction and trigger of further neuroinflammation and neurodegeneration. More research is necessary to elucidate the role of glucose-related metabolic processes in MS.\n                  <\/jats:p>","DOI":"10.1007\/s11011-026-01846-4","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T02:28:20Z","timestamp":1776392900000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cerebrospinal fluid glucose levels and their association with disability, depression, and cognitive function in multiple sclerosis"],"prefix":"10.1007","volume":"41","author":[{"given":"Lilith","family":"Hauck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Franz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Koerbel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Maiworm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Krueger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Zeltner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Hermanns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Baensch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilara","family":"Dabanli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharmili Edwin","family":"Thanarajah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yavor","family":"Yalachkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"1846_CR17","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s12974-016-0502-1","volume":"13","author":"M Albanese","year":"2016","unstructured":"Albanese M, Zagaglia S, Landi D et al (2016) Cerebrospinal fluid lactate is associated with multiple sclerosis disease progression. J Neuroinflammation 13:36. https:\/\/doi.org\/10.1186\/s12974-016-0502-1","journal-title":"J Neuroinflammation"},{"key":"1846_CR13","doi-asserted-by":"publisher","first-page":"e13288","DOI":"10.1111\/jne.13288","volume":"35","author":"H Ayromlou","year":"2023","unstructured":"Ayromlou H, Hosseini S, Khalili M et al (2023) Insulin resistance is associated with cognitive dysfunction in multiple sclerosis patients: A cross-sectional study. J Neuroendocrinol 35:e13288. https:\/\/doi.org\/10.1111\/jne.13288","journal-title":"J Neuroendocrinol"},{"key":"1846_CR24","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s40035-025-00467-8","volume":"14","author":"L Chen","year":"2025","unstructured":"Chen L, Wang C, Qin L, Zhang H (2025) Parkinson\u2019s disease and glucose metabolism impairment. Transl Neurodegener 14:10. https:\/\/doi.org\/10.1186\/s40035-025-00467-8","journal-title":"Transl Neurodegener"},{"key":"1846_CR23","doi-asserted-by":"publisher","unstructured":"Duz OA, Bektas S, Askin AE, Birday E (2022) An unexpected post-ocrelizumab improvement in Glycaemic control in a patient with multiple sclerosis. EMJ. https:\/\/doi.org\/10.33590\/emjdiabet\/10089148","DOI":"10.33590\/emjdiabet\/10089148"},{"key":"1846_CR8","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1515\/cclm-2014-0077","volume":"52","author":"H Hegen","year":"2014","unstructured":"Hegen H, Auer M, Deisenhammer F (2014) Serum glucose adjusted cut-off values for normal cerebrospinal fluid\/serum glucose ratio: implications for clinical practice. Clin Chem Lab Med 52:1335\u20131340. https:\/\/doi.org\/10.1515\/cclm-2014-0077","journal-title":"Clin Chem Lab Med"},{"key":"1846_CR7","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1007\/s00424-020-02441-x","volume":"472","author":"H Koepsell","year":"2020","unstructured":"Koepsell H (2020) Glucose transporters in brain in health and disease. Pflugers Arch 472:1299\u20131343. https:\/\/doi.org\/10.1007\/s00424-020-02441-x","journal-title":"Pflugers Arch"},{"issue":"4","key":"1846_CR5","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.neuron.2015.03.035","volume":"86","author":"J Pierre","year":"2015","unstructured":"Magistretti PJ, Allaman I (2015) A cellular perspective on brain energy metabolism and functional imaging. Neuron 86(4), 883\u2013901. https:\/\/doi.org\/10.1016\/j.neuron.2015.03.035","journal-title":"Neuron"},{"key":"1846_CR9","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1212\/WNL.0b013e3181d6b125","volume":"74","author":"RA Marrie","year":"2010","unstructured":"Marrie RA, Rudick R, Horwitz R et al (2010) Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis. Neurology 74:1041\u20131047. https:\/\/doi.org\/10.1212\/WNL.0b013e3181d6b125","journal-title":"Neurology"},{"key":"1846_CR4","doi-asserted-by":"publisher","first-page":"250","DOI":"10.3389\/fneur.2014.00250","volume":"5","author":"D Mathur","year":"2014","unstructured":"Mathur D, L\u00f3pez-Rodas G, Casanova B, Marti MB (2014) Perturbed glucose metabolism: insights into multiple sclerosis pathogenesis. Front Neurol 5:250. https:\/\/doi.org\/10.3389\/fneur.2014.00250","journal-title":"Front Neurol"},{"key":"1846_CR12","doi-asserted-by":"publisher","first-page":"101415","DOI":"10.1016\/j.msard.2019.101415","volume":"36","author":"H Noori","year":"2019","unstructured":"Noori H, Gheini MR, Rezaeimanesh N et al (2019) The correlation between dyslipidemia and cognitive impairment in multiple sclerosis patients. Mult Scler Relat Disord 36:101415. https:\/\/doi.org\/10.1016\/j.msard.2019.101415","journal-title":"Mult Scler Relat Disord"},{"key":"1846_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2020.102533","author":"H Ormstad","year":"2020","unstructured":"Ormstad H, Simonsen CS, Broch L et al (2020) Chronic fatigue and depression due to multiple sclerosis: immune-inflammatory pathways, tryptophan catabolites and the gut-brain axis as possible shared pathways. Multiple Scler Relat Disorders. 46. https:\/\/doi.org\/10.1016\/j.msard.2020.102533","journal-title":"Multiple Scler Relat Disorders"},{"key":"1846_CR25","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1186\/s12974-024-03218-0","volume":"21","author":"C Otto","year":"2024","unstructured":"Otto C, Kalantzis R, K\u00fcbler-Weller D et al (2024) Comprehensive analysis of the cerebrospinal fluid and serum metabolome in neurological diseases. J Neuroinflammation 21:234. https:\/\/doi.org\/10.1186\/s12974-024-03218-0","journal-title":"J Neuroinflammation"},{"key":"1846_CR1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1111\/ane.12651","volume":"134","author":"I-K Penner","year":"2016","unstructured":"Penner I-K (2016) Evaluation of cognition and fatigue in multiple sclerosis: daily practice and future directions. Acta Neurol Scand 134:19\u201323. https:\/\/doi.org\/10.1111\/ane.12651","journal-title":"Acta Neurol Scand"},{"key":"1846_CR14","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.jns.2008.07.032","volume":"275","author":"WT Regenold","year":"2008","unstructured":"Regenold WT, Phatak P, Makley MJ et al (2008) Cerebrospinal fluid evidence of increased extra-mitochondrial glucose metabolism implicates mitochondrial dysfunction in multiple sclerosis disease progression. J Neurol Sci 275:106\u2013112. https:\/\/doi.org\/10.1016\/j.jns.2008.07.032","journal-title":"J Neurol Sci"},{"key":"1846_CR11","doi-asserted-by":"publisher","first-page":"e70006","DOI":"10.1002\/edm2.70006","volume":"7","author":"N Rezaeimanesh","year":"2024","unstructured":"Rezaeimanesh N, Abbasi Kasbi N, Saeedi R et al (2024) Investigating the Correlation Between Cognitive Function and Fasting Blood Sugar, Fasting Insulin Level and Insulin Sensitivity in Patients With Multiple Sclerosis. Endocrinol Diabetes Metabolism 7:e70006. https:\/\/doi.org\/10.1002\/edm2.70006","journal-title":"Endocrinol Diabetes Metabolism"},{"key":"1846_CR10","doi-asserted-by":"publisher","unstructured":"Richeh W, Gutierrez A, Lovera J (2013) The association between serum glucose level and disability progression in multiple sclerosis (P04.130). Neurology 80:P04.130-P04.130 https:\/\/doi.org\/10.1212\/WNL.80.7_supplement.P04.130","DOI":"10.1212\/WNL.80.7_supplement.P04.130"},{"key":"1846_CR6","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1038\/s41393-025-01143-4","volume":"63","author":"T Rudroff","year":"2025","unstructured":"Rudroff T (2025) Spinal cord metabolism in multiple sclerosis: a decade of missed opportunities and future directions. Spinal Cord 63:642\u2013647. https:\/\/doi.org\/10.1038\/s41393-025-01143-4","journal-title":"Spinal Cord"},{"key":"1846_CR16","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1007\/s00115-004-1729-0","volume":"75","author":"P Scherer","year":"2004","unstructured":"Scherer P, Baum K, Bauer H et al (2004) Normierung der Brief Repeatable Battery of Neuropsychological Tests (BRB-N) f\u00fcr den deutschsprachigen Raum. Nervenarzt 75:984\u2013990. https:\/\/doi.org\/10.1007\/s00115-004-1729-0","journal-title":"Nervenarzt"},{"key":"1846_CR18","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1007\/s11011-024-01347-2","volume":"39","author":"M Sepidarkish","year":"2024","unstructured":"Sepidarkish M, Kalantari N, Gorgani-Firouzjaee T et al (2024) Association between insulin resistance and multiple sclerosis: a systematic review and meta-analysis. Metab Brain Dis 39:1015\u20131026. https:\/\/doi.org\/10.1007\/s11011-024-01347-2","journal-title":"Metab Brain Dis"},{"key":"1846_CR20","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s41983-020-0155-y","volume":"56","author":"RH Soliman","year":"2020","unstructured":"Soliman RH, Farhan HM, Hegazy M et al (2020) Impact of insulin resistance and metabolic syndrome on disability in patients with multiple sclerosis. Egypt J Neurol Psychiatry Neurosurg 56:18. https:\/\/doi.org\/10.1186\/s41983-020-0155-y","journal-title":"Egypt J Neurol Psychiatry Neurosurg"},{"key":"1846_CR15","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1111\/1755-5922.12049","volume":"32","author":"Z Sternberg","year":"2014","unstructured":"Sternberg Z, Leung C, Sternberg D et al (2014) Disease Modifying Therapies Modulate Cardiovascular Risk Factors in Patients with Multiple Sclerosis. Cardiovasc Ther 32:33\u201339. https:\/\/doi.org\/10.1111\/1755-5922.12049","journal-title":"Cardiovasc Ther"},{"key":"1846_CR19","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1186\/ar4688","volume":"16","author":"RH Straub","year":"2014","unstructured":"Straub RH (2014) Insulin resistance, selfish brain, and selfish immune system: an evolutionarily positively selected program used in chronic inflammatory diseases. Arthritis Res Ther 16:S4. https:\/\/doi.org\/10.1186\/ar4688","journal-title":"Arthritis Res Ther"},{"key":"1846_CR2","doi-asserted-by":"publisher","unstructured":"Tarasiuk J, Kapica-Topczewska K, Czarnowska A et al (2022) Co-occurrence of Fatigue and Depression in People With Multiple Sclerosis: A Mini-Review. Front Neurol 12. https:\/\/doi.org\/10.3389\/fneur.2021.817256","DOI":"10.3389\/fneur.2021.817256"},{"key":"1846_CR22","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1007\/s12031-020-01672-y","volume":"71","author":"TO Tobore","year":"2021","unstructured":"Tobore TO (2021) Oxidative\/Nitroxidative Stress and Multiple Sclerosis. J Mol Neurosci 71:506\u2013514. https:\/\/doi.org\/10.1007\/s12031-020-01672-y","journal-title":"J Mol Neurosci"},{"key":"1846_CR26","doi-asserted-by":"publisher","first-page":"100901","DOI":"10.1016\/j.bbih.2024.100901","volume":"42","author":"AFK Vizuete","year":"2024","unstructured":"Vizuete AFK, Fr\u00f3es F, Seady M et al (2024) Targeting glycolysis for neuroprotection in early LPS-induced neuroinflammation. Brain Behav Immun Health 42:100901. https:\/\/doi.org\/10.1016\/j.bbih.2024.100901","journal-title":"Brain Behav Immun Health"},{"key":"1846_CR21","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1177\/1352458513515957","volume":"20","author":"I Wens","year":"2014","unstructured":"Wens I, Dalgas U, Deckx N et al (2014) Does multiple sclerosis affect glucose tolerance? Mult Scler 20:1273\u20131276. https:\/\/doi.org\/10.1177\/1352458513515957","journal-title":"Mult Scler"}],"container-title":["Metabolic Brain Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11011-026-01846-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11011-026-01846-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11011-026-01846-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:14:54Z","timestamp":1781648094000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11011-026-01846-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,17]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1846"],"URL":"https:\/\/doi.org\/10.1007\/s11011-026-01846-4","relation":{},"ISSN":["1573-7365"],"issn-type":[{"value":"1573-7365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,17]]},"assertion":[{"value":"13 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All human and animal studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Standards"}},{"value":"Lilith Hauck has been supported by travel grants from Merck and Juvise. Yavor Yalachkov has been supported by travel grants from Alexion, argenx, Novartis and Sanofi and has received honoraria for active participation in advisory boards and speaker\/writing honoraria by Alexion, Amgen, argenx, Bristol Meyers Squibb, Juvise, Kassen\u00e4rztliche Vereinigung Hessen, Landes\u00e4rztekammer Hessen, Merck, Neuraxpharm, Novartis, RG Gesellschaft f\u00fcr Information und Organization mbH, Roche, Sanofi, TEVA; his research is funded by Deutsche Forschungsgemeinschaft (DFG), Fachbereich Medizin der Goethe-Universit\u00e4t Frankfurt, Heinrich und Erna Schaufler Stiftung, Roche and Novartis. Kimberly Koerbel is a participant at the Junior Clinician Scientist Program funded by Goethe University Frankfurt and received speaker honoraria by Novartis. Michelle Maiworm received speaking honoraria from Roche, Synlab and Novartis; her research was funded by the Faculty of Medicine at the Goethe University Frankfurt and the Goethe Research Academy for Early Career Researchers (GRADE) of the Goethe University Frankfurt, the Heinrich und Erna Schaufler-Foundation as well as the MS Foundation of the State of Hesse. Valentin Krueger Merck has been supported by Merck (travel and congress grants), Novartis (speaker honoraria) as well as UCB (travel and congress grants). Sharmili Edwin Thanarajah served in a advisory board of Janssen and received speakers honoraria from Janssen and Medice. None of this honoraria has been received specifically for this project. The other authors declare that they have no conflicts of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"82"}}