{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T01:43:20Z","timestamp":1776131000029,"version":"3.50.1"},"reference-count":120,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Multiple sclerosis (MS) is a chronic neurological disorder characterized by inflammation in the central nervous system (CNS) that leads to neurodegeneration. The clinical course is highly variable, but its prevalence is rising worldwide, partly thanks to novel disease-modifying therapies. Additionally, the lifespan of people with MS is increasing, and for this reason, it is fundamental to have a multidisciplinary approach to MS. MS may be associated with cardiovascular diseases (CVD), but there is scarce attention on this issue. In particular, CNS is essential in regulating the autonomic system and heart activity. Moreover, cardiovascular risk factors show a higher prevalence in MS patients. On the other hand, conditions like Takotsubo syndrome are rare complications of MS. The parallelism between MS and myocarditis is also interesting. Finally, cardiac toxicity represents a not infrequent adverse reaction to MS drugs. This narrative review aims to provide an overview of cardiovascular complications in MS and their management to prompt further clinical and pre-clinical research on this topic.<\/jats:p>","DOI":"10.3390\/jcdd10040153","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T01:37:05Z","timestamp":1680485825000},"page":"153","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Heart\u2013Brain Interplay in Multiple Sclerosis from Pathophysiology to Clinical Practice: A Narrative Review"],"prefix":"10.3390","volume":"10","author":[{"given":"Matteo","family":"Zavarella","sequence":"first","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2858-1404","authenticated-orcid":false,"given":"Andrea","family":"Villatore","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Myocarditis Disease Unit, IRCCS San Raffaele Scientific Institute, 20019 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Assunta","family":"Rocca","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Neurology Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1815-4000","authenticated-orcid":false,"given":"Giovanni","family":"Peretto","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Myocarditis Disease Unit, IRCCS San Raffaele Scientific Institute, 20019 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-0479","authenticated-orcid":false,"given":"Massimo","family":"Filippi","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Neurology Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Neurophysiology Service, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/s41572-018-0041-4","article-title":"Multiple sclerosis","volume":"4","author":"Filippi","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/s41590-018-0135-x","article-title":"Reassessing B cell contributions in multiple sclerosis","volume":"19","author":"Li","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nri3871","article-title":"Immunopathology of multiple sclerosis","volume":"15","author":"Dendrou","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1093\/brain\/awh641","article-title":"Cortical demyelination and diffuse white matter injury in multiple sclerosis","volume":"128","author":"Kutzelnigg","year":"2005","journal-title":"Brain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1136\/jnnp-2011-300616","article-title":"Relative mortality and survival in multiple sclerosis: Findings from British Columbia, Canada","volume":"83","author":"Kingwell","year":"2012","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1212\/WNL.0000000000001718","article-title":"Effect of comorbidity on mortality inmultiple sclerosis","volume":"85","author":"Marrie","year":"2015","journal-title":"Neurology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1177\/1352458514564491","article-title":"A systematic review of the incidence and prevalence of comorbidity in multiple sclerosis: Overview","volume":"21","author":"Marrie","year":"2015","journal-title":"Mult. Scler. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/j.1468-1331.2009.02814.x","article-title":"Multiple sclerosis survival: A population-based study in Sicily","volume":"17","author":"Ragonese","year":"2010","journal-title":"Eur. J. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1136\/jnnp-2015-310361","article-title":"Mortality in multiple sclerosis: Meta-analysis of standardised mortality ratios","volume":"87","author":"Manouchehrinia","year":"2016","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s10286-021-00790-w","article-title":"Cardiac autonomic function in patients with early multiple sclerosis","volume":"31","author":"Imrich","year":"2021","journal-title":"Clin. Auton. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1177\/1352458514564485","article-title":"A systematic review of the incidence and prevalence of cardiac, cerebrovascular, and peripheral vascular disease in multiple sclerosis","volume":"21","author":"Marrie","year":"2015","journal-title":"Mult. Scler. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nrneurol.2017.33","article-title":"Comorbidity in multiple sclerosis: Implications for patient care","volume":"13","author":"Marrie","year":"2017","journal-title":"Nat. Rev. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100291","DOI":"10.1016\/j.lanwpc.2021.100291","article-title":"Cardiovascular disease prevention: Risk factor modification at the heart of the matter","volume":"17","author":"Fawzy","year":"2021","journal-title":"Lancet Reg. Health West. Pac."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.cjca.2010.12.040","article-title":"Chronic inflammatory diseases and cardiovascular risk: A systematic review","volume":"27","author":"Roifman","year":"2011","journal-title":"Can. J. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/jemt.1060100205","article-title":"Morphology of synapses in the autonomic nervous system","volume":"10","author":"Smolen","year":"1988","journal-title":"J. Electron Microsc. Tech."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1146\/annurev.ne.15.030192.002033","article-title":"The Role of the Amygdala in Fear and Anxiety","volume":"15","author":"Davis","year":"1992","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Cersosimo, M.G., and Benarroch, E.E. (2013). Central Control of Autonomic Function and Involvement in Neurodegenerative Disorders, Elsevier. [1st ed.].","DOI":"10.1016\/B978-0-444-53491-0.00005-5"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1016\/S0735-1097(02)01852-1","article-title":"Autonomic nervous system influences on qt interval in normal subjects","volume":"39","author":"Magnano","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1177\/135245850100700509","article-title":"Autonomic dysfunction in multiple sclerosis is related to disease activity and progression of disability","volume":"7","author":"Flachenecker","year":"2001","journal-title":"Mult. Scler. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/(SICI)1097-0185(199702)247:2<289::AID-AR15>3.0.CO;2-L","article-title":"Gross and microscopic anatomy of the human intrinsic cardiac nervous system","volume":"247","author":"Armour","year":"1997","journal-title":"Anat. Rec."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.hrthm.2010.02.014","article-title":"Functional anatomy of intrathoracic neurons innervating the atria and ventricles","volume":"7","author":"Armour","year":"2010","journal-title":"Hear. Rhythm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s10286-019-00605-z","article-title":"Immune and autonomic nervous system interactions in multiple sclerosis: Clinical implications","volume":"29","author":"Habek","year":"2019","journal-title":"Clin. Auton. Res."},{"key":"ref_23","first-page":"1","article-title":"Autonomic dysfunctions in multiple sclerosis: Challenges of clinical practice (Review)","volume":"20","author":"Sirbu","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/0022-510X(93)90029-X","article-title":"Cardiovascular autonomic dysfunction in multiple sclerosis is likely related to brainstem lesions","volume":"120","author":"Vita","year":"1993","journal-title":"J. Neurol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s10286-016-0370-x","article-title":"Sympathetic cardiovascular and sudomotor functions are frequently affected in early multiple sclerosis","volume":"26","author":"Habek","year":"2016","journal-title":"Clin. Auton. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1016\/j.clinph.2004.01.012","article-title":"Cardiovascular autonomic dysfunction correlates with brain MRI lesion load in MS","volume":"115","author":"Saari","year":"2004","journal-title":"Clin. Neurophysiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s004150170204","article-title":"Autonomic dysfunction in multiple sclerosis: Cervical spinal cord atrophy correlates","volume":"248","author":"Stojkovic","year":"2001","journal-title":"J. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e00742","DOI":"10.1002\/brb3.742","article-title":"The impact of multiple sclerosis onset symptom on cardiac repolarization","volume":"7","author":"Mikkola","year":"2017","journal-title":"Brain Behav."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1002\/1097-4598(200008)23:8<1284::AID-MUS21>3.0.CO;2-R","article-title":"Cardiac repolarization abnormalities in multiple sclerosis: Spinal cord MRI correlates","volume":"23","author":"Stojkovic","year":"2000","journal-title":"Muscle Nerve."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1159\/000469707","article-title":"Postural Orthostatic Tachycardia Predicts Early Conversion to Multiple Sclerosis after Clinically Isolated Syndrome","volume":"77","author":"Habek","year":"2017","journal-title":"Eur. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.tcm.2021.03.001","article-title":"Cardiovascular pathophysiology from the cardioneural perspective and its clinical applications","volume":"32","author":"Shah","year":"2022","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s10286-015-0325-7","article-title":"Autonomic dysfunction, immune regulation, and multiple sclerosis","volume":"26","author":"Racosta","year":"2016","journal-title":"Clin. Auton. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1152\/jappl.1991.71.4.1563","article-title":"Pharmacological dissection of components of the Valsalva maneuver in adrenergic failure","volume":"71","author":"Sandroni","year":"1991","journal-title":"J. Appl. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1007\/s004150050407","article-title":"Cardiovascular autonomic dysfunction in multiple sclerosis: Correlation with orthostatic intolerance","volume":"246","author":"Flachenecker","year":"1999","journal-title":"J. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1212\/WNL.0000000000006942","article-title":"Autonomic nervous system and neuroimmune interactions","volume":"92","author":"Benarroch","year":"2019","journal-title":"Neurology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/nri1810","article-title":"Neural regulation of innate immunity: A coordinated nonspecific host response to pathogens","volume":"6","author":"Sternberg","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1001\/jamaneurol.2020.0664","article-title":"Evaluating the Risk of Macrovascular Events and Mortality Among People With Multiple Sclerosis in England","volume":"77","author":"Palladino","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"103279","DOI":"10.1016\/j.msard.2021.103279","article-title":"Associations between multiple sclerosis and incidence of heart diseases: Systematic review and meta-analysis of observational studies","volume":"56","author":"Rapp","year":"2021","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6407","DOI":"10.1007\/s10072-022-06345-9","article-title":"Prevalence of chronic comorbidities in people with multiple sclerosis: Descriptive study based on administrative data in Tuscany (Central Italy)","volume":"43","author":"Bezzini","year":"2022","journal-title":"Neurol Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1177\/1352458514533162","article-title":"An adverse lipid profile is associated with disability and progression in disability, in people with MS","volume":"20","author":"Tettey","year":"2014","journal-title":"Mult. Scler. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1001\/archneurol.2009.122","article-title":"Smoking and disease progression in multiple sclerosis","volume":"66","author":"Healy","year":"2009","journal-title":"Arch. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1159\/000320245","article-title":"Risk of arterial cardiovascular diseases in patients with multiple sclerosis: A population-based cohort study","volume":"35","author":"Christiansen","year":"2010","journal-title":"Neuroepidemiology"},{"key":"ref_43","first-page":"CD012732","article-title":"Rehabilitation for people with multiple sclerosis: An overview of Cochrane Reviews","volume":"1","author":"Amatya","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_44","first-page":"223","article-title":"Is long-term exercise intervention effective to improve cardiac autonomic control during exercise in subjects with multiple sclerosis? A randomized controlled trial\u2013PubMed","volume":"51","author":"Hansen","year":"2015","journal-title":"Eur. J. Phys. Rehabil. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1136\/jnnp.47.9.947","article-title":"Evidence for cardiovascular autonomic nerve dysfunction in multiple sclerosis","volume":"47","author":"Senaratne","year":"1984","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/pri.416","article-title":"Clinical screening of autonomic dysfunction in multiple sclerosis","volume":"14","author":"Hale","year":"2009","journal-title":"Physiother Res Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3233\/NRE-130938","article-title":"Exercise-onset heart rate increase is slowed in multiple sclerosis patients: Does a disturbed cardiac autonomic control affect exercise tolerance?","volume":"33","author":"Hansen","year":"2013","journal-title":"Neurorehabilitation"},{"key":"ref_48","first-page":"223","article-title":"Is long-term exercise intervention effective to improve cardiac autonomic control during exercisein subjects with multiple sclerosis? A randomized controlled trial","volume":"51","author":"Hansen","year":"2015","journal-title":"Eur. J. Phys. Rehabil. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jns.2016.05.050","article-title":"Muscular, cardiac, ventilatory and metabolic dysfunction in patients with multiple sclerosis: Implications for screening, clinical care and endurance and resistance exercise therapy, a scoping review","volume":"367","author":"Wens","year":"2016","journal-title":"J. Neurol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s12471-010-0049-1","article-title":"ECG Changes in Subarachnoid Haemorrhage: A Synopsis","volume":"19","author":"Chatterjee","year":"2011","journal-title":"Neth. Heart J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/0002-8703(67)90047-6","article-title":"Central nervous system mechanisms mediating cardiac rate and rhythm","volume":"74","author":"Mauck","year":"1967","journal-title":"Am. Heart J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S1474-4422(11)70291-5","article-title":"Cardiovascular and neurological causes of sudden death after ischaemic stroke","volume":"11","author":"Hachinski","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1159\/000135711","article-title":"Cardiac arrhythmias after subarachnoid hemorrhage: Risk factors and impact on outcome","volume":"26","author":"Frontera","year":"2008","journal-title":"Cerebrovasc. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1136\/pgmj.62.727.385","article-title":"Paroxysmal atrial fibrillation associated with an attack of multiple sclerosis","volume":"62","author":"Chagnac","year":"1986","journal-title":"Postgrad. Med. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.resuscitation.2005.11.003","article-title":"Cardiogenic shock in a young female with multiple sclerosis","volume":"70","author":"Uriel","year":"2006","journal-title":"Resuscitation"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.hlc.2012.06.003","article-title":"Neurocardiogenic pulmonary oedema: Initial presentation of multiple sclerosis","volume":"21","author":"Padley","year":"2012","journal-title":"Heart Lung Circ."},{"key":"ref_57","first-page":"1153","article-title":"The brain-heart connection: A multiple sclerosis relapse presenting as Takotsubo Syndrome. A case report and literature review","volume":"90","author":"Sciatti","year":"2020","journal-title":"Monaldi Arch. Chest Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.1742-1241.2008.01833.x","article-title":"Tako-tsubo-like left ventricular dysfunction: Transient left ventricular apical ballooning syndrome","volume":"64","author":"Vizzardi","year":"2010","journal-title":"Int. J. Clin. Pract."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1016\/j.jacc.2009.02.020","article-title":"Stress Cardiomyopathy After Intravenous Administration of Catecholamines and Beta-Receptor Agonists","volume":"53","author":"Abraham","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1093\/eurheartj\/ehy076","article-title":"International expert consensus document on takotsubo syndrome (Part I): Clinical characteristics, diagnostic criteria, and pathophysiology","volume":"39","author":"Ghadri","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/jcu.22066","article-title":"Biventricular Tako-Tsubo cardiomyopathy: Usefulness of 2D speckle tracking strain echocardiography","volume":"42","author":"Vizzardi","year":"2014","journal-title":"J. Clin. Ultrasound"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1177\/1352458516638557","article-title":"An uncommon first manifestation of multiple sclerosis: Tako-Tsubo cardiomyopathy","volume":"22","author":"Midaglia","year":"2016","journal-title":"Mult. Scler. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.msard.2018.09.021","article-title":"Multiple sclerosis relapse presenting as an acute cardiomyopathy","volume":"27","author":"Bayer","year":"2019","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.msard.2018.05.005","article-title":"A case of Takotsubo syndrome during a multiple sclerosis brainstem relapse","volume":"24","author":"Prestipino","year":"2018","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1161\/CIRCRESAHA.113.302549","article-title":"Role of the autonomic nervous system in modulating cardiac arrhythmias","volume":"114","author":"Shen","year":"2014","journal-title":"Circulation Research."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1161\/01.CIR.94.6.1329","article-title":"Clinically silent electrocardiographic abnormalities and risk of primary cardiac arrest among hypertensive patients","volume":"94","author":"Siscovick","year":"1996","journal-title":"Circulation"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.hrthm.2009.05.006","article-title":"Predictive value of electrocardiographic QT interval and T-wave morphology parameters for all-cause and cardiovascular mortality in a general population sample","volume":"6","author":"Porthan","year":"2009","journal-title":"Heart Rhythm."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1056\/NEJMra052130","article-title":"Multiple Sclerosis\u2013The Plaque and Its Pathogenesis","volume":"354","author":"Frohman","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nrneurol.2012.168","article-title":"Progressive multiple sclerosis: Pathology and pathogenesis","volume":"8","author":"Lassmann","year":"2012","journal-title":"Nat. Rev. Neurol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1093\/eurheartj\/eht210","article-title":"Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases","volume":"34","author":"Caforio","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s00059-005-2730-5","article-title":"Inflammatory Dilated Cardiomyopathy (DCMI)","volume":"30","author":"Maisch","year":"2005","journal-title":"Herz"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0165-5728(00)00295-2","article-title":"Cytokines and immunity in multiple sclerosis: The dual signal hypothesis","volume":"109","author":"Martino","year":"2000","journal-title":"J. Neuroimmunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1097\/BOR.0b013e328353372d","article-title":"Update on coxsackievirus B3 myocarditis","volume":"24","author":"Fairweather","year":"2012","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4004","DOI":"10.4049\/jimmunol.1001718","article-title":"Th17 Cells Contribute to Viral Replication in Coxsackievirus B3-Induced Acute Viral Myocarditis","volume":"185","author":"Yuan","year":"2010","journal-title":"J. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1093\/eurjhf\/hfr014","article-title":"Expression of functional T-cell markers and T-cell receptor Vbeta repertoire in endomyocardial biopsies from patients presenting with acute myocarditis and dilated cardiomyopathy","volume":"13","author":"Noutsias","year":"2011","journal-title":"Eur. J. Heart Fail."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1253\/jcj.65.1082","article-title":"Th1\/Th2 Balance Alteration in the Clinical Course of a Patient With Acute Viral Myocarditis","volume":"65","author":"Fuse","year":"2001","journal-title":"Jpn. Circ. J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1056\/NEJMoa1601277","article-title":"Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis","volume":"376","author":"Hauser","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e89","DOI":"10.1212\/NXI.0000000000000089","article-title":"MOG cell-based assay detects non-MS patients with inflammatory neurologic disease","volume":"2","author":"Waters","year":"2015","journal-title":"Neurol Neuroimmunol. Neuroinflamm."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1161\/CIRCULATIONAHA.106.641472","article-title":"Prospective Familial Assessment in Dilated Cardiomyopathy","volume":"115","author":"Caforio","year":"2007","journal-title":"Circulation"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1161\/01.CIR.85.5.1734","article-title":"Identification of alpha- and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy","volume":"85","author":"Caforio","year":"1992","journal-title":"Circulation"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1126\/science.abj8222","article-title":"Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis","volume":"375","author":"Bjornevik","year":"2022","journal-title":"Science"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1038\/cti.2017.25","article-title":"Defective T-cell control of Epstein\u2013Barr virus infection in multiple sclerosis","volume":"6","author":"Pender","year":"2017","journal-title":"Clin. Transl. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"VRicigliano, V.A.G., Handel, A.E., Sandve, G.K., Annibali, V., Ristori, G., Mechelli, R., Cader, M.Z., and Salvetti, M. (2015). EBNA2 Binds to Genomic Intervals Associated with Multiple Sclerosis and Overlaps with Vitamin D Receptor Occupancy. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119605"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/s41569-020-00435-x","article-title":"Myocarditis and inflammatory cardiomyopathy: Current evidence and future directions","volume":"18","author":"Ammirati","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s15010-012-0321-y","article-title":"An unusual presentation of a common infection","volume":"41","author":"Richter","year":"2013","journal-title":"Infection"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1002\/ehf2.12611","article-title":"Infarct-like myocarditis with coronary vasculitis and aneurysm formation caused by Epstein\u2013Barr virus infection","volume":"7","author":"Chimenti","year":"2020","journal-title":"ESC Heart Fail."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"593","DOI":"10.2217\/fvl.12.44","article-title":"Regulatory T cells and Th17 cells in viral infections: Implications for multiple sclerosis and myocarditis","volume":"7","author":"Sato","year":"2012","journal-title":"Futur. Virol."},{"key":"ref_88","first-page":"85851","article-title":"Cardiac myosin-Th17 responses promote heart failure in human myocarditis","volume":"1","author":"Myers","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1365-2567.2007.02690.x","article-title":"Compromised CD4+ CD25highregulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the single-cell level","volume":"123","author":"Venken","year":"2008","journal-title":"Immunology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1093\/eurheartj\/ehaa286","article-title":"Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection","volume":"41","author":"Sala","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Peretto, G., Villatore, A., Rizzo, S., Esposito, A., De Luca, G., Palmisano, A., Vignale, D., Cappelletti, A., Tresoldi, M., and Campochiaro, C. (2021). The Spectrum of COVID-19-Associated Myocarditis: A Patient-Tailored Multidisciplinary Approach. J. Clin. Med., 10.","DOI":"10.3390\/jcm10091974"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Kaufmann, C.C., Villatore, A., Heugl, M., Kvakan, H., Zweiker, D., Sala, S., Mazzone, P., Huber, K., and Peretto, G. (2023). Cardiac inflammation associated with COVID-19 mRNA vaccination in patients with and without previous myocarditis. Minerva Cardioangiol., 71.","DOI":"10.23736\/S2724-5683.22.06204-4"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"100299","DOI":"10.1016\/j.ensci.2020.100299","article-title":"A first presentation of multiple sclerosis with concurrent COVID-19 infection","volume":"22","author":"Moore","year":"2021","journal-title":"Eneurologicalsci"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"102377","DOI":"10.1016\/j.msard.2020.102377","article-title":"Multiple sclerosis following SARS-CoV-2 infection","volume":"45","author":"Palao","year":"2020","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_95","first-page":"1","article-title":"Demyelinating Changes Alike to Multiple Sclerosis: A Case Report of Rare Manifestations of COVID-19","volume":"2020","author":"Yavari","year":"2020","journal-title":"Case Rep. Neurol. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1002\/jmv.25728","article-title":"The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients","volume":"92","author":"Li","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"755333","DOI":"10.3389\/fimmu.2021.755333","article-title":"Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?","volume":"12","author":"Bellucci","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"577785","DOI":"10.1016\/j.jneuroim.2021.577785","article-title":"New diagnosis of multiple sclerosis in the setting of mRNA COVID-19 vaccine exposure","volume":"362","author":"Toljan","year":"2022","journal-title":"J. Neuroimmunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-21599-0","article-title":"Impaired Cardiac Function in Patients with Multiple Sclerosis by Comparison with Normal Subjects","volume":"8","author":"Mincu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/j.1600-0404.2006.00662.x","article-title":"Subclinical left ventricular dysfunction in multiple sclerosis","volume":"114","author":"Akgul","year":"2006","journal-title":"Acta Neurol. Scand."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1056\/NEJMcpc079030","article-title":"Case 36-2007","volume":"357","author":"Sabatine","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1056\/NEJMc073493","article-title":"Case 36-2007: A woman with rash, fever, and hypotension","volume":"358","author":"Ghei","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_103","first-page":"1406","article-title":"Case 36-2007: A woman with rash, fever, and hypotension","volume":"358","author":"Descamps","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1056\/NEJMc073493","article-title":"Case 36-2007: A woman with rash, fever, and hypotension","volume":"358","author":"Fett","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e46","DOI":"10.1212\/CPJ.0000000000000772","article-title":"Alemtuzumab and Fatal Myocarditis","volume":"11","author":"Scolding","year":"2021","journal-title":"Neurol. Clin. Pract."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e09","DOI":"10.15420\/cfr.2020.33","article-title":"Fatal Enterovirus-related Myocarditis in a Patient with Devic\u2019s Syndrome Treated with Rituximab","volume":"7","author":"Diarra","year":"2021","journal-title":"Card. Fail. Rev."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1177\/1352458513495939","article-title":"Myocarditis and diffuse skeletal muscle oedema: New features of neuromyelitis optica spectrum disorder? A case report","volume":"20","author":"Cosgrove","year":"2014","journal-title":"Mult. Scler. J."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s40265-020-01431-8","article-title":"Sphingosine 1-phosphate Receptor Modulator Therapy for Multiple Sclerosis: Differential Downstream Receptor Signalling and Clinical Profile Effects","volume":"81","author":"Chun","year":"2021","journal-title":"Drugs"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1016\/S0140-6736(02)12023-X","article-title":"Mitoxantrone in progressive multiple sclerosis: A placebo-controlled, double-blind, randomised, multicentre trial","volume":"360","author":"Hartung","year":"2002","journal-title":"Lancet"},{"key":"ref_110","first-page":"111","article-title":"Mitoxantrone-induced cardiotoxicity in patients with multiple sclerosis","volume":"9","author":"Hamzehloo","year":"2006","journal-title":"Arch Iran Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"211","DOI":"10.4103\/ijpvm.IJPVM_477_17","article-title":"Late cardiotoxicity in MS patients treated with mitoxantrone","volume":"10","author":"Najafian","year":"2019","journal-title":"Int. J. Prev. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jns.2011.07.018","article-title":"Incidence of various cardiac arrhythmias and conduction disturbances due to high dose intravenous methylprednisolone in patients with multiple sclerosis","volume":"309","author":"Sahraian","year":"2011","journal-title":"J. Neurol. Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.ahj.2014.06.028","article-title":"Cardiac and vascular effects of fingolimod: Mechanistic basis and clinical implications","volume":"168","author":"Camm","year":"2014","journal-title":"Am. Hear. J."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1586\/14737175.2016.1123094","article-title":"Fingolimod: A review of its mode of action in the context of its efficacy and safety profile in relapsing forms of multiple sclerosis","volume":"16","author":"Jeffery","year":"2016","journal-title":"Expert Rev. Neurother."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1177\/1352458511410344","article-title":"Delayed fingolimod-associated asystole","volume":"17","author":"Espinosa","year":"2011","journal-title":"Mult. Scler. J."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Br\u00e6nne, I., Zeng, L., Willenborg, C., Tragante, V., Kessler, T., CARDIoGRAM Consortium, CARDIoGRAMplusC4D Consortium, Willer, C.J., Laakso, M., and Wallentin, L. (2017). Genomic correlates of glatiramer acetate adverse cardiovascular effects lead to a novel locus mediating coronary risk. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0182999"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"102438","DOI":"10.1016\/j.msard.2020.102438","article-title":"Long-term safety and efficacy of teriflunomide in patients with relapsing multiple sclerosis: Results from the TOWER extension study","volume":"46","author":"Miller","year":"2020","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_118","first-page":"2783","article-title":"Protective effect of dimethyl fumarate on oxidative damage and signaling in cardiomyocytes","volume":"22","author":"Kuang","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1177\/1352458519851219","article-title":"Emerging safety issues in alemtuzumab-treated MS patients","volume":"25","author":"Killestein","year":"2019","journal-title":"Mult. Scler. J."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.ijcard.2022.05.052","article-title":"Novel multiple sclerosis agents-associated cardiotoxicity: A real-world pharmacovigilance study","volume":"362","author":"Abduljabar","year":"2022","journal-title":"Int. J. Cardiol."}],"container-title":["Journal of Cardiovascular Development and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3425\/10\/4\/153\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:08:07Z","timestamp":1760123287000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3425\/10\/4\/153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,1]]},"references-count":120,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["jcdd10040153"],"URL":"https:\/\/doi.org\/10.3390\/jcdd10040153","relation":{},"ISSN":["2308-3425"],"issn-type":[{"value":"2308-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,1]]}}}