{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:43:09Z","timestamp":1785404589145,"version":"3.56.0"},"reference-count":118,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010301","name":"University of Kragujevac","doi-asserted-by":"publisher","award":["JP 07\/19"],"award-info":[{"award-number":["JP 07\/19"]}],"id":[{"id":"10.13039\/501100010301","id-type":"DOI","asserted-by":"publisher"}]},{"award":["JP 07\/19"],"award-info":[{"award-number":["JP 07\/19"]}],"id":[{"id":"https:\/\/ror.org\/04f7vj627","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["NeuroSci"],"abstract":"<jats:p>Background: Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system. Our study aimed to examine the relationship between serum iron levels and the following clinical parameters: depression, anxiety, fatigue, neuropathic pain, and disease activity on magnetic resonance imaging in patients with relapsing-remitting multiple sclerosis (RRMS). Material and methods: This study was designed as a clinical observational, cross-sectional study. This study was conducted at the Clinic of Neurology of the University Clinical Center Kragujevac, from 2022 to 2024, according to the ethical code of the Declaration of Helsinki. Demographic and clinical data on patients were obtained from the medical history. All MS patients were diagnosed according to the McDonald criteria (2017). This study included 65 patients in the experimental group and 11 healthy individuals in the control group, with an average age of 39.68 years. Serum iron levels were biochemically analyzed from venous blood. The following standardized tests were used to collect data on depression, anxiety, fatigue, and neuropathic pain: Beck Depression Inventory (BDI), Hamilton Anxiety Rating Scale (HAM-A), Modified Fatigue Impact Scale (MFIS), PainDETECT Questionnaire (PD-Q), and Visual Analogue Scale (VAS). Results: Serum iron level significantly correlates with disease activity on magnetic resonance imaging in patients with multiple sclerosis. Serum iron showed a moderate positive correlation with hemoglobin, hematocrit, total and direct bilirubin, and a weak positive correlation with uric acid, while a moderate negative correlation was observed with erythrocyte sedimentation rate. No statistically significant difference was found between serum iron levels and depression, anxiety, fatigue, and severity of neuropathic pain. The ROC curves show the diagnostic potential of the combined parameters in differentiating RRMS from controls, as well as the potential of iron in differentiating active from inactive MS. The presence of disease, hemoglobin and total bilirubin were recorded as significant independent predictors. Conclusion: This study is a descriptive attempt to present the potential role of iron in the radiological activity of the disease. High serum iron level may be associated with radiological disease activity in patients with multiple sclerosis.<\/jats:p>","DOI":"10.3390\/neurosci7040086","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:11:56Z","timestamp":1785168716000},"page":"86","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Influence of Serum Iron Levels on Depression, Anxiety, Fatigue, Neuropathic Pain and MR Disease Activity in Patients with Multiple Sclerosis"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6124-9965","authenticated-orcid":false,"given":"Simonida","family":"Delic","sequence":"first","affiliation":[{"name":"Department of Anatomy, Faculty of Medical Sciences Kragujevac, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana Miletic","family":"Drakulic","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medical Sciences Kragujevac, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snezana","family":"Lazarevic","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medical Sciences Kragujevac, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6740-0215","authenticated-orcid":false,"given":"Milos","family":"Stepovic","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medical Sciences Kragujevac, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3722-4102","authenticated-orcid":false,"given":"Nikoleta","family":"Janicijevic","sequence":"additional","affiliation":[{"name":"Department of Hygiene and Ecology, Faculty of Medical Sciences Kragujevac, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Vulovic","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medical Sciences Kragujevac, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Mitrovic Zivanovic","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Clinical Centre Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danica","family":"Igrutinovic","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University Clinical Centre Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanija","family":"Tepavcevic","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medical Sciences Kragujevac, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milica","family":"Dimitrijevic","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medical Sciences Kragujevac, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Department of Plastic Surgery, University Clinical Centre Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Manojlovic","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, University Clinical Centre Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3179-6043","authenticated-orcid":false,"given":"Bojana","family":"Markovic","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Clinical Centre Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0822-3554","authenticated-orcid":false,"given":"Nebojsa","family":"Igrutinovic","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Clinical Centre Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0248-3590","authenticated-orcid":false,"given":"Vladimir","family":"Markovic","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Fundamentals of Oncology, Faculty of Medical Sciences Kragujevac, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Department of Microbiology and Immunology, University Clinical Centre Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Azanjac","family":"Arsic","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medical Sciences Kragujevac, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bizo\u0144, A., Chojdak-\u0141ukasiewicz, J., Budrewicz, S., Pokryszko-Dragan, A., and Piwowar, A. (2023). Exploring the Relationship between Antioxidant Enzymes, Oxidative Stress Markers, and Clinical Profile in Relapsing-Remitting Multiple Sclerosis. Antioxidants, 12.","DOI":"10.3390\/antiox12081638"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17562864211066751","DOI":"10.1177\/17562864211066751","article-title":"Smouldering multiple sclerosis: The \u2018real MS\u2019","volume":"15","author":"Giovannoni","year":"2022","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1212\/WNL.0000000000000560","article-title":"Defining the clinical course of multiple sclerosis: The 2013 revisions","volume":"83","author":"Lublin","year":"2014","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"a028928","DOI":"10.1101\/cshperspect.a028928","article-title":"Clinical Course of Multiple Sclerosis","volume":"8","author":"Klineova","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s12291-016-0614-5","article-title":"Role of Iron and Copper in the Pathogenesis of Parkinson\u2019s Disease","volume":"32","author":"Gangania","year":"2017","journal-title":"Indian J. Clin. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Delic, S., Miletic Drakulic, S., Stepovic, M., Milosavljevic, J., Kovacevic Dimitrijevic, M., Jovanovic, K., Marinkovic, I., Tepavcevic, M., Janicijevic, N., and Mitrovic, A. (2025). The Connection Between Oxidative Stress, Mitochondrial Dysfunction, Iron Metabolism and Microglia in Multiple Sclerosis: A Narrative Review. NeuroSci, 6.","DOI":"10.3390\/neurosci6010023"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"725370","DOI":"10.1155\/2015\/725370","article-title":"Inflammation, Iron, Energy Failure, and Oxidative Stress in the Pathogenesis of Multiple Sclerosis","volume":"2015","author":"Haider","year":"2015","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1552-6569.2008.00296.x","article-title":"Deep gray matter involvement on brain MRI scans is associated with clinical progression in multiple sclerosis","volume":"19","author":"Neema","year":"2009","journal-title":"J. Neuroimaging"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1002\/glia.20416","article-title":"Cellular iron status influences the functional relationship between microglia and oligodendrocytes","volume":"54","author":"Zhang","year":"2006","journal-title":"Glia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1002\/acn3.50893","article-title":"Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis","volume":"6","author":"Magliozzi","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Dusek, P., Hofer, T., Alexander, J., Roos, P.M., and Aaseth, J.O. (2022). Cerebral Iron Deposition in Neurodegeneration. Biomolecules, 12.","DOI":"10.3390\/biom12050714"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Dal-Bianco, A., Schranzer, R., Grabner, G., Lanzinger, M., Kolbrink, S., Pusswald, G., Altmann, P., Ponleitner, M., Weber, M., and Kornek, B. (2021). Iron Rims in Patients With Multiple Sclerosis as Neurodegenerative Marker? A 7-Tesla Magnetic Resonance Study. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.632749"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jad.2015.09.074","article-title":"The association between serum ferritin levels and post-stroke depression","volume":"190","author":"Zhu","year":"2016","journal-title":"J. Affect. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41598-016-0018-z","article-title":"Serotonergic dysfunctions and abnormal iron metabolism: Relevant to mental fatigue of Parkinson disease","volume":"6","author":"Zuo","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"515","DOI":"10.3325\/cmj.2019.60.515","article-title":"Association of ferritin levels with depression, anxiety, sleep quality, and physical functioning in patients with fibromyalgia syndrome: A cross-sectional study","volume":"60","author":"Okan","year":"2019","journal-title":"Croat. Med. J."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Knyszy\u0144ska, A., Radecka, A., Zabielska, P., \u0141uczak, J., Karakiewicz, B., and Lubkowska, A. (2020). The Role of Iron Metabolism in Fatigue, Depression, and Quality of Life in Multiple Sclerosis Patients. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17186818"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"104934","DOI":"10.1016\/j.msard.2023.104934","article-title":"Iron in multiple sclerosis\u2014Neuropathology, immunology, and real-world considerations","volume":"78","author":"Zierfuss","year":"2023","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"105788","DOI":"10.1016\/j.neubiorev.2024.105788","article-title":"The iron maiden: Oligodendroglial metabolic dysfunction in multiple sclerosis and mitochondrial signaling","volume":"164","author":"Emamnejad","year":"2024","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s40478-025-02020-0","article-title":"Inflammation alters myeloid cell and oligodendroglial iron-handling in multiple sclerosis","volume":"13","author":"Riedl","year":"2025","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_20","first-page":"e93005","article-title":"Serum Iron and Ferritin in Patients with Multiple Sclerosis","volume":"15","author":"Iranmanesh","year":"2013","journal-title":"Zahedan J. Res. Med. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"75","DOI":"10.55782\/ane-2025-2680","article-title":"Iron in multiple sclerosis\u2014From pathophysiology to disease progression\u2014A narrative literature review","volume":"85","author":"Januszewski","year":"2025","journal-title":"Acta Neurobiol. Exp."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Duarte-Silva, E., Meuth, S.G., and Peixoto, C.A. (2023). The role of iron metabolism in the pathogenesis and treatment of multiple sclerosis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1137635"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1093\/brain\/awaa436","article-title":"Long-term evolution of multiple sclerosis iron rim lesions in 7 T MRI","volume":"144","author":"Grabner","year":"2021","journal-title":"Brain"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1007\/s00115-018-0550-0","article-title":"Diagnose der Multiplen Sklerose: Revision der McDonald-Kriterien 2017","volume":"89","author":"Aktas","year":"2018","journal-title":"Der Nervenarzt."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e1334","DOI":"10.1212\/WNL.0000000000012603","article-title":"Association of Age With Contrast-Enhancing Lesions Across the Multiple Sclerosis Disease Spectrum","volume":"97","author":"Koch","year":"2021","journal-title":"Neurology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1001\/archneur.60.8.1089","article-title":"Pain in patients with multiple sclerosis: A population-based study","volume":"60","author":"Svendsen","year":"2003","journal-title":"Arch. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1176\/appi.neuropsych.20220124","article-title":"Neuropsychiatric Status of Patients with Multiple Sclerosis Across Disease Duration Intervals","volume":"35","author":"Freedman","year":"2023","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"104506","DOI":"10.1016\/j.msard.2023.104506","article-title":"Characterization of a late-onset multiple sclerosis Portuguese cohort","volume":"70","author":"Moura","year":"2023","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0003-2697(82)90118-X","article-title":"Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids","volume":"126","author":"Green","year":"1982","journal-title":"Anal. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0022-1759(80)90340-3","article-title":"A simple colorimetric method for the measurement of hydrogen peroxide produced by cells in culture","volume":"38","author":"Pick","year":"1980","journal-title":"J. Immunol. Methods"},{"key":"ref_32","unstructured":"Greenwald, R.A. (1985). Nitroblue tetrazolium reduction. Handbook of Methods for Oxygen Radical Research, CRC Press."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0076-6879(84)05016-3","article-title":"Catalase in vitro","volume":"105","author":"Aebi","year":"1984","journal-title":"Methods Enzymol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3170","DOI":"10.1016\/S0021-9258(19)45228-9","article-title":"The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase","volume":"247","author":"Misra","year":"1972","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0021-9258(19)68028-2","article-title":"A spectrophotometric method for the determination of reduced glutathione","volume":"233","author":"Lipkin","year":"1958","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1212\/WNL.33.11.1444","article-title":"Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS)","volume":"33","author":"Kurtzke","year":"1983","journal-title":"Neurology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1093\/brain\/awac016","article-title":"How patients with multiple sclerosis acquire disability","volume":"145","author":"Lublin","year":"2022","journal-title":"Brain"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"106","DOI":"10.26641\/2307-0404.2023.2.283349","article-title":"Anxiety and depression in patients with multiple sclerosis","volume":"28","author":"Somilo","year":"2023","journal-title":"Med. Perspekt."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Meyer-Moock, S., Feng, Y.S., Maeurer, M., Dippel, F.W., and Kohlmann, T. (2014). Systematic literature review and validity evaluation of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) in patients with multiple sclerosis. BMC Neurol., 14.","DOI":"10.1186\/1471-2377-14-58"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1159\/000029042","article-title":"Beck Depression Inventory in the detection of depression among neurological inpatients","volume":"31","author":"Lykouras","year":"1998","journal-title":"Psychopathology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1037\/pro0000556","article-title":"Brief Mood Survey Concurrent Validation With the Beck Depression Inventory\u2013II and the Symptom Checklist\u201390\u2013Revised: An Efficient Tool to Improve Treatment Monitoring","volume":"55","author":"Whittemore","year":"2024","journal-title":"Prof. Psychol. Res. Pract."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.2044-8341.1959.tb00467.x","article-title":"The assessment of anxiety states by rating","volume":"32","author":"Hamilton","year":"1959","journal-title":"Br. J. Med. Psychol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/mpr.323","article-title":"Identifying HAM-A cutoffs for mild, moderate, and severe generalized anxiety disorder","volume":"19","author":"Matza","year":"2010","journal-title":"Int. J. Methods Psychiatr. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15","DOI":"10.7224\/1537-2073.2012-019","article-title":"Psychometric properties of the modified fatigue impact scale","volume":"15","author":"Larson","year":"2013","journal-title":"Int. J. MS Care"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1191\/1352458502ms839oa","article-title":"Fatigue in multiple sclerosis: A comparison of different rating scales and correlation to clinical parameters","volume":"8","author":"Flachenecker","year":"2002","journal-title":"Mult. Scler."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"105798","DOI":"10.1016\/j.msard.2024.105798","article-title":"Associations between fatigue impact and physical and neurobehavioural factors: An exploration in people with progressive multiple sclerosis","volume":"90","author":"Connolly","year":"2024","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"102576","DOI":"10.1016\/j.msard.2020.102576","article-title":"Tired of not knowing what that fatigue score means? Normative data of the Modified Fatigue Impact Scale (MFIS)","volume":"46","author":"Strober","year":"2020","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1185\/030079906X132488","article-title":"painDETECT: A new screening questionnaire to identify neuropathic components in patients with back pain","volume":"22","author":"Freynhagen","year":"2006","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Packham, T.L., Cappelleri, J.C., Sadosky, A., MacDermid, J.C., and Brunner, F. (2017). Measurement properties of painDETECT: Rasch analysis of responses from community-dwelling adults with neuropathic pain. BMC Neurol., 17.","DOI":"10.1186\/s12883-017-0825-2"},{"key":"ref_50","first-page":"497","article-title":"Measurement properties of painDETECT by average pain severity","volume":"6","author":"Cappelleri","year":"2014","journal-title":"ClinicoEcon. Outcomes Res."},{"key":"ref_51","first-page":"574","article-title":"Measurement of pain using the visual numeric scale","volume":"33","author":"Ritter","year":"2006","journal-title":"J. Rheumatol."},{"key":"ref_52","first-page":"2055217319885984","article-title":"Serum hepcidin levels in multiple sclerosis","volume":"5","author":"Bsteh","year":"2019","journal-title":"Mult. Scler. J. Exp. Transl. Clin."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1177\/1352458507085550","article-title":"The role of iron dysregulation in the pathogenesis of multiple sclerosis: An Egyptian study","volume":"14","author":"Rashed","year":"2008","journal-title":"Mult. Scler."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.neuro.2006.12.001","article-title":"Serum chemical elements and oxidative status in Alzheimer\u2019s disease, Parkinson disease and multiple sclerosis","volume":"28","author":"Alimonti","year":"2007","journal-title":"Neurotoxicology"},{"key":"ref_55","first-page":"217","article-title":"Concentration of elements in serum of patients affected by multiple sclerosis with first demyelinating episode: A six-month longitudinal follow-up study","volume":"41","author":"Visconti","year":"2005","journal-title":"Ann. Ist. Super. Sanita"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1191\/1352458505ms1171oa","article-title":"Serum ferritin, transferrin and soluble transferrin receptor levels in multiple sclerosis patients","volume":"11","author":"Sfagos","year":"2005","journal-title":"Mult. Scler."},{"key":"ref_57","first-page":"213","article-title":"Quantification of chemical elements in blood of patients affected by multiple sclerosis","volume":"41","author":"Forte","year":"2005","journal-title":"Ann. Ist. Super. Sanita"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1017\/S0317167100028869","article-title":"Abnormalities in iron metabolism in multiple sclerosis","volume":"16","author":"Valberg","year":"1989","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1054\/mehy.2000.1051","article-title":"The possible role of gradual accumulation of copper, cadmium, lead and iron and gradual depletion of zinc, magnesium, selenium, vitamins B2, B6, D, and E and essential fatty acids in multiple sclerosis","volume":"55","author":"Johnson","year":"2000","journal-title":"Med. Hypotheses"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/eji.202149589","article-title":"Sex differences regulate immune responses in experimental autoimmune encephalomyelitis and multiple sclerosis","volume":"52","author":"Ryan","year":"2022","journal-title":"Eur. J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Nytrova, P., and Dolezal, O. (2022). Sex bias in multiple sclerosis and neuromyelitis optica spectrum disorders: How it influences clinical course, MRI parameters and prognosis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.933415"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1212\/CPJ.0000000000001105","article-title":"How Multiple Sclerosis Symptoms Vary by Age, Sex, and Race\/Ethnicity","volume":"11","author":"Kister","year":"2021","journal-title":"Neurol. Clin. Pract."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"105749","DOI":"10.1016\/j.msard.2024.105749","article-title":"Impact of sex on clinical outcome in early Multiple Sclerosis","volume":"88","author":"Gottwald","year":"2024","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"S51","DOI":"10.1016\/j.neurobiolaging.2014.03.039","article-title":"Iron and multiple sclerosis","volume":"35","author":"Stankiewicz","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.jns.2016.12.039","article-title":"Disease progression and oxidative stress are associated with higher serum ferritin levels in patients with multiple sclerosis","volume":"373","author":"Ferreira","year":"2017","journal-title":"J. Neurol. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Stojkovic, L., Djordjevic, A., Stefanovic, M., Stankovic, A., Dincic, E., Djuric, T., and Zivkovic, M. (2024). Circulatory Indicators of Lipid Peroxidation, the Driver of Ferroptosis, Reflect Differences between Relapsing-Remitting and Progressive Multiple Sclerosis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252011024"},{"key":"ref_67","first-page":"121","article-title":"Iron and the folate-vitamin B12-methylation pathway in multiple sclerosis","volume":"21","author":"Kotze","year":"2006","journal-title":"Metab. Brain Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jtemb.2019.05.011","article-title":"Serum NADPH oxidase concentrations and the associations with iron metabolism in relapsing remitting multiple sclerosis","volume":"55","author":"Yildiz","year":"2019","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"36","DOI":"10.4236\/ojmn.2012.23008","article-title":"The Haematological Profile of Patients with Multiple Sclerosis","volume":"2","author":"Hon","year":"2012","journal-title":"Open J. Mod. Neurosurg."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.33594\/000000814","article-title":"Peripheral Inflammation as a Biomarker of Disease Activity in Relapsing-Remitting MS","volume":"32","author":"Abdullah","year":"2025","journal-title":"Neurosignals"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"104","DOI":"10.2174\/1871527311312010016","article-title":"The prevalence of the classical and non-classical cardiovascular risk factors in multiple sclerosis patients","volume":"12","author":"Sternberg","year":"2013","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_72","first-page":"1306","article-title":"Does anxiety, depression, and sleep levels affect the quality of life in patients diagnosed with multiple sclerosis?","volume":"28","author":"Dogan","year":"2024","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s004150170158","article-title":"Serum inflammatory markers and clinical\/MRI markers of disease progression in multiple sclerosis","volume":"248","author":"Giovannoni","year":"2001","journal-title":"J. Neurol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.jocn.2012.05.054","article-title":"Serum uric acid level in patients with relapsing-remitting multiple sclerosis","volume":"20","author":"Ashtari","year":"2013","journal-title":"J. Clin. Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.clineuro.2005.08.004","article-title":"Serum uric acid and multiple sclerosis","volume":"108","author":"Rentzos","year":"2006","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1007\/s00415-015-7666-y","article-title":"Uric acid in relapsing-remitting multiple sclerosis: A 2-year longitudinal study","volume":"262","author":"Moccia","year":"2015","journal-title":"J. Neurol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.5937\/jomb0-51901","article-title":"An assessment of an antioxidative status in patients with multiple sclerosis using standard biochemical analyses","volume":"44","year":"2025","journal-title":"J. Med. Biochem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.1007\/s10072-020-04928-y","article-title":"Superoxide dismutase (SOD), advanced oxidation protein products (AOPP), and disease-modifying treatment are related to better relapse recovery after corticosteroid treatment in multiple sclerosis","volume":"42","author":"Obradovic","year":"2021","journal-title":"Neurol. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1126\/science.3029864","article-title":"Bilirubin is an antioxidant of possible physiological importance","volume":"235","author":"Stocker","year":"1987","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1179\/016164106X98215","article-title":"Uric acid in multiple sclerosis","volume":"28","author":"Koch","year":"2006","journal-title":"Neurol. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"P5.2-011","DOI":"10.1212\/WNL.92.15_supplement.P5.2-011","article-title":"Loss of Brain Iron is Linked to Disability in Multiple Sclerosis\u2014The Difference Between Concentration and Mass of Iron","volume":"92","author":"Hagemeier","year":"2019","journal-title":"Neurology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"103967","DOI":"10.1016\/j.msard.2022.103967","article-title":"Spatial distribution of multiple sclerosis iron rim lesions and their impact on disability","volume":"64","author":"Wittayer","year":"2022","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jneuroim.2007.03.020","article-title":"The involvement of mitochondria in the pathogenesis of multiple sclerosis","volume":"188","author":"Kalman","year":"2007","journal-title":"J. Neuroimmunol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Williams, R., Rohr, A.M., Wang, W.T., Choi, I.Y., Lee, P., Berman, N.E., Lynch, S.G., and LeVine, S.M. (2011). Iron deposition is independent of cellular inflammation in a cerebral model of multiple sclerosis. BMC Neurosci., 12.","DOI":"10.1186\/1471-2202-12-59"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1002\/hbm.25306","article-title":"Decreasing brain iron in multiple sclerosis: The difference between concentration and content in iron MRI","volume":"42","author":"Schweser","year":"2021","journal-title":"Hum. Brain Mapp."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s41747-022-00279-9","article-title":"Iron deposition in multiple sclerosis: Overall load or distribution alteration?","volume":"6","author":"Hamdy","year":"2022","journal-title":"Eur. Radiol. Exp."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Jim\u00e9nez-Jim\u00e9nez, F.J., Alonso-Navarro, H., Salgado-C\u00e1mara, P., Garc\u00eda-Mart\u00edn, E., and Ag\u00fandez, J.A.G. (2024). Oxidative Stress Markers in Multiple Sclerosis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25126289"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1007\/s00234-025-03595-0","article-title":"Neurodegeneration correlates of iron-related lesions and leptomeningeal inflammation in multiple sclerosis clinical subtypes","volume":"67","author":"Vakrakou","year":"2025","journal-title":"Neuroradiology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1097\/WCO.0000000000000946","article-title":"Central vein sign and iron rim in multiple sclerosis: Ready for clinical use?","volume":"34","author":"Preziosa","year":"2021","journal-title":"Curr. Opin. Neurol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/s00401-023-02627-4","article-title":"Myeloid cell iron uptake pathways and paramagnetic rim formation in multiple sclerosis","volume":"146","author":"Hofmann","year":"2023","journal-title":"Acta Neuropathol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"119503","DOI":"10.1016\/j.neuroimage.2022.119503","article-title":"Susceptibility networks reveal independent patterns of brain iron abnormalities in multiple sclerosis","volume":"261","author":"Reeves","year":"2022","journal-title":"Neuroimage"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1002\/ana.23974","article-title":"Iron and neurodegeneration in the multiple sclerosis brain","volume":"74","author":"Hametner","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/s41423-022-00883-0","article-title":"Ferroptosis promotes T-cell activation-induced neurodegeneration in multiple sclerosis","volume":"19","author":"Luoqian","year":"2022","journal-title":"Cell. Mol. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"104106","DOI":"10.1016\/j.msard.2022.104106","article-title":"High-intensity resistance training in people with multiple sclerosis experiencing fatigue: A randomised controlled trial","volume":"68","author":"Englund","year":"2022","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.neurol.2022.10.004","article-title":"NUTRISEP: Assessment of the nutritional status of patients with multiple sclerosis and link to fatigue","volume":"179","author":"Massot","year":"2023","journal-title":"Rev. Neurol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1017\/S0007114517001349","article-title":"Iron deficiency without anaemia is a potential cause of fatigue: Meta-analyses of randomised controlled trials and cross-sectional studies","volume":"117","author":"Yokoi","year":"2017","journal-title":"Br. J. Nutr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"317","DOI":"10.33588\/rn.7811.2024092","article-title":"Utilidad de la escala de depresi\u00f3n de Beck para el diagn\u00f3stico de los trastornos depresivos en la esclerosis m\u00faltiple [Usefulness of the Beck depression inventory in the diagnosis of depressive disorders in multiple sclerosis]","volume":"78","year":"2024","journal-title":"Rev. Neurol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.psychres.2016.12.039","article-title":"Insulin resistance, atherogenicity, and iron metabolism in multiple sclerosis with and without depression: Associations with inflammatory and oxidative stress biomarkers and uric acid","volume":"250","author":"Oliveira","year":"2017","journal-title":"Psychiatry Res."},{"key":"ref_99","first-page":"69","article-title":"Factors Associated with Depression and Anxiety Severity in Multiple Sclerosis Patients","volume":"1","author":"Seferoglu","year":"2021","journal-title":"J. Mult. Scler. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1055\/s-0043-1761492","article-title":"Correlation of brain segmental volume changes with clinical parameters: A longitudinal study in multiple sclerosis patients","volume":"81","author":"Eskut","year":"2023","journal-title":"Arq. Neuro-Psiquiatr."},{"key":"ref_101","first-page":"30","article-title":"Assessment of depression and anxiety in patients with multiple sclerosis depending on disease severity according to the EDSS","volume":"21","author":"Lafarenko","year":"2025","journal-title":"Int. Neurol. J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1097\/j.pain.0000000000002136","article-title":"Characterizing chronic pain phenotypes in multiple sclerosis: A nationwide survey study","volume":"162","author":"Kratz","year":"2021","journal-title":"Pain"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41572-023-00484-9","article-title":"Central neuropathic pain","volume":"9","author":"Rosner","year":"2023","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"105401","DOI":"10.1016\/j.neubiorev.2023.105401","article-title":"A systematic review and meta-analysis of neuropathic pain in multiple sclerosis: Prevalence, clinical types, sex dimorphism, and increased depression and anxiety symptoms","volume":"154","author":"Rodrigues","year":"2023","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_105","first-page":"31","article-title":"Pain in patients with multiple sclerosis","volume":"69","author":"Kasap","year":"2022","journal-title":"Turk. J. Phys. Med. Rehabil."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1093\/abm\/kaaa102","article-title":"Early Treatment Improvements in Depression Are Associated With Overall Improvements in Fatigue Impact and Pain Interference in Adults With Multiple Sclerosis","volume":"55","author":"Knowles","year":"2021","journal-title":"Ann. Behav. Med."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Meng, S.H., Zhou, H.B., Li, X., Wang, M.X., Kang, L.X., Fu, J.M., Li, X., Li, X.T., and Zhao, Y.S. (2021). Association Between Dietary Iron Intake and Serum Ferritin and Severe Headache or Migraine. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.685564"},{"key":"ref_108","first-page":"676","article-title":"Association Between Iron Deficiency Anemia and Chronic Daily Headache","volume":"3","author":"Saleem","year":"2023","journal-title":"J. Health Rehabil. Res."},{"key":"ref_109","first-page":"44","article-title":"Iron Deficiency without Anemia as a Cause of Treatable Headache: A Pilot Study","volume":"28","year":"2020","journal-title":"Qual. Prim. Care"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/s41398-023-02555-7","article-title":"Depressive symptoms, anxiety and cognitive impairment: Emerging evidence in multiple sclerosis","volume":"13","author":"Margoni","year":"2023","journal-title":"Transl. Psychiatry"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"104431","DOI":"10.1016\/j.msard.2022.104431","article-title":"Clinical correlates of state and trait anxiety in multiple sclerosis","volume":"69","author":"Menculini","year":"2023","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Yin, R., Gao, Q., Fu, G., and Zhao, Q. (2024). The causal effect of iron status on risk of anxiety disorders: A two-sample Mendelian randomization study. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0300143"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1038\/s41589-019-0371-x","article-title":"Axonal iron transport in the brain modulates anxiety-related behaviors","volume":"15","author":"Wang","year":"2019","journal-title":"Nat. Chem. Biol."},{"key":"ref_114","first-page":"e18138","article-title":"Iron Deficiency-Induced Changes in the Hippocampus, Corpus Striatum, and Monoamines Levels That Lead to Anxiety, Depression, Sleep Disorders, and Psychotic Disorders","volume":"13","author":"Shah","year":"2021","journal-title":"Cureus"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1177\/19714009241303123","article-title":"Quantitative susceptibility mapping of the fear circuit: Associations with silent symptoms in relapsing-remitting multiple sclerosis","volume":"38","author":"Khormi","year":"2025","journal-title":"Neuroradiol. J."},{"key":"ref_116","first-page":"5","article-title":"Serum Iron and Zinc Levels in Lebanese Multiple Sclerosis Patients","volume":"29","author":"Matar","year":"2020","journal-title":"Acta Neurol. Taiwanica"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Ptaszek, B., Podsiad\u0142o, S., Czerwi\u0144ska-Ledwig, O., Maciejczyk, M., and Teleg\u0142\u00f3w, A. (2022). Effect of Whole-Body Cryotherapy on Iron Status and Biomarkers of Neuroplasticity in Multiple Sclerosis Women. Healthcare, 10.","DOI":"10.3390\/healthcare10091681"},{"key":"ref_118","first-page":"2832","article-title":"Prevalence of Iron Overload in Patients with Multiple Sclerosis","volume":"6","author":"Alanazi","year":"2023","journal-title":"J. Med. Chem. Sci."}],"container-title":["NeuroSci"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2673-4087\/7\/4\/86\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:47:48Z","timestamp":1785322068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2673-4087\/7\/4\/86"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":118,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["neurosci7040086"],"URL":"https:\/\/doi.org\/10.3390\/neurosci7040086","relation":{},"ISSN":["2673-4087"],"issn-type":[{"value":"2673-4087","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]}}}