{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T02:35:45Z","timestamp":1786761345789,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>This study assessed cardiac autonomic response to head-up tilt test (HUTT) in 23 myasthenia gravis (MG) and 23 relapsing-remitting multiple sclerosis (RRMS) patients compared to 30 healthy controls (HC). Task Force\u00ae Monitor was used to evaluate cardiac inotropy parameters, baroreflex sensitivity (BRS), heart rate (HRV), and blood pressure variability (BPV) during HUTT. MG patients were characterized by reduced BRS (p &lt; 0.05), post-HUTT decrease in high-frequency component (p &lt; 0.05) and increase in sympathovagal ratio of HRV (p &lt; 0.05) when compared to controls indicating parasympathetic deficiency with a shift of sympathovagal balance toward sympathetic predominance. Compared to HC, MG patients also showed lower cardiac inotropy parameters, specifically, left ventricular work index (LVWI) during supine rest (p &lt; 0.05) as well as LVWI and cardiac index values in response to orthostatic stress (p &lt; 0.01 and p &lt; 0.05, respectively). Compared to controls, RRMS patients were characterized by lower HRV delta power spectral density (p &lt; 0.05) and delta low-frequency HRV (p &lt; 0.05) in response to HUTT suggesting combined sympathetic and parasympathetic dysfunction. There were no differences in cardiac autonomic parameters between MG and MS patients (p &gt; 0.05). Our study highlights the possibility of cardiac and autonomic dysfunction in patients with MG and RRMS which should be considered in the pharmacological and rehabilitation approach to managing these conditions.<\/jats:p>","DOI":"10.3390\/jcm10102173","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T06:01:33Z","timestamp":1621317693000},"page":"2173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Cardiac Autonomic Dysfunction in Myasthenia Gravis and Relapsing-Remitting Multiple Sclerosis\u2014A Pilot Study"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2995-6148","authenticated-orcid":false,"given":"\u0141ukasz","family":"Rzepi\u0144ski","sequence":"first","affiliation":[{"name":"Department of Neurology, 10th Military Research Hospital and Polyclinic, Powsta\u0144c\u00f3w Warszawy 5, 85-681 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3861-7113","authenticated-orcid":false,"given":"Monika","family":"Zawadka-Kunikowska","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Epidemiology, Ergonomy and Postgraduate Education, Ludwik Rydygier Collegium Medicum in Bydgoszcz Nicolaus Copernicus University in Torun, M. Sklodowskiej-Curie 9, 85-094 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia L.","family":"Newton","sequence":"additional","affiliation":[{"name":"Population Health Science Institute, The Medical School, Newcastle University, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8453-7785","authenticated-orcid":false,"given":"Pawe\u0142","family":"Zalewski","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Epidemiology, Ergonomy and Postgraduate Education, Ludwik Rydygier Collegium Medicum in Bydgoszcz Nicolaus Copernicus University in Torun, M. Sklodowskiej-Curie 9, 85-094 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s12974-017-0892-8","article-title":"Regulatory T cells in multiple sclerosis and myasthenia gravis","volume":"14","author":"Danikowski","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/cei.12260","article-title":"Neuroinflammation of the central and peripheral nervous system: An update","volume":"175","author":"Zettl","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41572-019-0079-y","article-title":"Myasthenia gravis","volume":"5","author":"Gilhus","year":"2019","journal-title":"Nat. Rev. Dis. Primer."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1016\/S0140-6736(18)30481-1","article-title":"Multiple sclerosis","volume":"391","author":"Thompson","year":"2018","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1093\/brain\/awaa385","article-title":"Neuregulin-1 beta 1 is implicated in pathogenesis of multiple sclerosis","volume":"12","author":"Kataria","year":"2021","journal-title":"Brain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.3389\/fimmu.2019.01990","article-title":"Systematic Review of Safety and Efficacy of Rituximab in Treating Immune-Mediated Disorders","volume":"10","author":"Kaegi","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.bbacli.2015.04.003","article-title":"Cognitive impairment as a central cholinergic deficit in patients with Myasthenia Gravis","volume":"3","author":"Kaltsatou","year":"2015","journal-title":"BBA Clin."},{"key":"ref_8","first-page":"209","article-title":"Evaluation of pupil mobility in patients with myasthenia gravis","volume":"48","author":"Tsiptsios","year":"2008","journal-title":"Electromyogr. Clin. Neurophysiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"709","DOI":"10.3389\/fneur.2020.00709","article-title":"Myasthenia Gravis Masquerading as an Idiopathic Unilateral Facial Paralysis (Bell's Palsy)-A Very Rare and Unique Clinical Find","volume":"11","author":"Elnazeir","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.18632\/aging.101896","article-title":"Autonomic dysfunction in neurological disorders","volume":"11","author":"Xiong","year":"2019","journal-title":"Aging"},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/B978-0-444-53491-0.00031-6","article-title":"Chapter 31\u2014Heart rate variability","volume":"Volume 117","author":"Buijs","year":"2013","journal-title":"Handbook of Clinical Neurology Autonomic Nervous System"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.clineuro.2012.05.013","article-title":"Abnormal sympathetic hyper-reactivity in patients with myasthenia gravis: A prospective study","volume":"115","author":"Shukla","year":"2013","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.cyto.2014.09.011","article-title":"T cell subsets and their signature cytokines in autoimmune and inflammatory diseases","volume":"74","author":"Raphael","year":"2015","journal-title":"Cytokine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1177\/1352458518763094","article-title":"Cytokine signaling in multiple sclerosis: Lost in translation","volume":"24","author":"Ruck","year":"2018","journal-title":"Mult. Scler."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"25886","DOI":"10.1038\/srep25886","article-title":"Changes in inflammatory cytokine networks in myasthenia gravis","volume":"6","author":"Uzawa","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1212\/WNL.0000000000006942","article-title":"Autonomic nervous system and neuroimmune interactions. New insights and clinical implications","volume":"92","author":"Benarroch","year":"2019","journal-title":"Neurology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/35013070","article-title":"Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin","volume":"405","author":"Borovikova","year":"2000","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S139","DOI":"10.33549\/physiolres.933671","article-title":"Vagal-immune interactions involved in cholinergic anti-inflammatory pathway","volume":"66","author":"Zila","year":"2017","journal-title":"Physiol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Gatta, V., Mengod, G., Reale, M., and Tata, A.M. (2020). Possible Correlation between Cholinergic System Alterations and Neuro\/Inflammation in Multiple Sclerosis. Biomedicines, 8.","DOI":"10.3390\/biomedicines8060153"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1002\/ana.22366","article-title":"Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria","volume":"69","author":"Polman","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1093\/brain\/awq076","article-title":"Evidence for a two-stage disability progression in multiple sclerosis","volume":"133","author":"Leray","year":"2010","journal-title":"Brain"},{"key":"ref_24","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_25","unstructured":"(2021, March 12). Definitions for a Standardised, Quantified Neurological Examinationand Assessment of Kurtzke\u2018s Functional Systems and ExpandedDisability Status Scale in Multiple Sclerosis. Available online: www.neurostatus.net\/media\/specimen\/Definitions_0410-2_s.pdf."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1212\/WNL.55.1.16","article-title":"Myasthenia gravis: Recommendations for clinical research standards. Task force of the medical scientific advisory board of the myasthenia gravis foundation of America","volume":"55","author":"JJaretzki","year":"2000","journal-title":"Neurology"},{"key":"ref_27","unstructured":"Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (1996). Assessment clinical autonomic testing report of the therapeutics and technology subcommittee of the American Academy of Neurology. Neurology, 46, 873\u2013880."},{"key":"ref_28","unstructured":"Schwalm, T. (2006). Modern Tilt Table Testing and Non-Invasive Monitoring. Traditional and Innovative Applications in Theory and Practice, ABW Wissenschaftsverlag GmbH."},{"key":"ref_29","unstructured":"Fortin, J., Klinger, T., Wagner, C., Sterner, H., Madritsch, C., Gr\u00fcllenberger, R., Hacker, A., Habenbacher, W., and Skrabal, F. (1998, January 1). The task force monitor\u2014A non-invasive beat-to beat monitor for hemodynamic and autonomic function of the human body. Proceedings of the 20th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Hong Kong, China."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1515\/bmte.1997.42.6.162","article-title":"Adaptive Autoregressive Modeling used for Single-trial EEG Classification\u2014Verwendung eines Adaptiven Autoregressiven Modells f\u00fcr die Klassifikation von Einzeltrial-EEG-Daten","volume":"42","author":"Flotzinger","year":"1997","journal-title":"Biomed. Tech."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0010-4825(98)00005-5","article-title":"A software package for non-invasive, real-time beat-to-beat monitoring of stroke volume, blood pressure, total peripheral resistance and for assessment of autonomic function","volume":"28","author":"Gratze","year":"1998","journal-title":"Comput. Biol Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1093\/oxfordjournals.eurheartj.a014868","article-title":"Heart rate variability: Standards of measurement, physiological interpretation, and clinical use","volume":"17","author":"Malik","year":"1996","journal-title":"Eur. Hear. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/00004872-200018010-00003","article-title":"How to measure baroreflex sensitivity: From the cardiovascular laboratory to daily life","volume":"18","author":"Parati","year":"2000","journal-title":"J. Hypertens."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/psyp.12027","article-title":"The utility of low frequency heart rate variability as an index of sympathetic cardiac tone: A review with emphasis on a reanalysis of previous studies","volume":"50","author":"Langewitz","year":"2013","journal-title":"Psychophysiology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1093\/oxfordjournals.eurheartj.a014868","article-title":"Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology","volume":"17","author":"Malik","year":"1996","journal-title":"Eur. Heart. J."},{"key":"ref_36","unstructured":"(2021, March 15). NIST\/SEMATECH e-Handbook of Statistical Methods, Available online: http:\/\/www.itl.nist.gov\/div898\/handbook."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1111\/eci.12553","article-title":"Sympathetic activation in cardiovascular disease: Evidence, clinical impact and therapeutic implications","volume":"45","author":"Grassi","year":"2015","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1007\/s00415-014-7465-x","article-title":"The presence of dysautonomia in different subgroups of myasthenia gravis patients","volume":"261","year":"2014","journal-title":"J. Neurol."},{"key":"ref_39","first-page":"179","article-title":"Cardiac involvement in myasthenia gravis--is there a specific pattern?","volume":"47","author":"Savu","year":"2009","journal-title":"Rom. J. Intern. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/8058946","article-title":"Electrocardiography as the First Step for the Further Examination of Cardiac Involvement in Myasthenia Gravis","volume":"2016","author":"Kato","year":"2016","journal-title":"BioMed. Res. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ijcme.2014.08.003","article-title":"Cardiac manifestations of myasthenia gravis: A systematic review","volume":"5","author":"Shivamurthya","year":"2014","journal-title":"IJC Metab. Endocr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1001\/archneur.62.3.442","article-title":"Striational antibodies in myasthenia gravis: Reactivity and possible clinical significance","volume":"62","author":"Romi","year":"2005","journal-title":"Arch. Neurol."},{"key":"ref_43","unstructured":"(2021, March 15). Cardiac Dysfunction in Myasthenic Crisis. Available online: http:\/\/oaji.net\/articles\/2015\/1626-1445873445.pdf."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1007\/s00415-008-0049-x","article-title":"Left ventricular long axis function in myasthenia gravis","volume":"255","author":"Owe","year":"2008","journal-title":"J. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"42","DOI":"10.4103\/aian.AIAN_270_17","article-title":"The Spectrum of Autonomic Dysfunction in Myasthenic Crisis","volume":"21","author":"Benjamin","year":"2018","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1080\/01616412.2018.1446690","article-title":"Evaluation of cardiac autonomic functions in myasthenia gravis","volume":"40","author":"Kocabas","year":"2018","journal-title":"Neurol. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.autneu.2008.09.005","article-title":"Autonomic ganglia, acetylcholine receptor antibodies, and autoimmune ganglionopathy","volume":"146","author":"Vernino","year":"2009","journal-title":"Auton. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ydbio.2018.10.017","article-title":"The role of agrin, Lrp4 and MuSK during dendritic arborization and synaptogenesis in cultured embryonic CNS neurons","volume":"445","author":"Handara","year":"2019","journal-title":"Dev. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.neuint.2012.02.028","article-title":"The role of agrin in synaptic development, plasticity and signaling in the central nervous system","volume":"61","author":"Daniels","year":"2012","journal-title":"Neurochem. Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4604","DOI":"10.1242\/dev.150110","article-title":"Neuronal LRP4 regulates synapse formation in the developing CNS","volume":"144","author":"Karakatsani","year":"2017","journal-title":"Development"},{"key":"ref_51","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_52","doi-asserted-by":"crossref","unstructured":"Studer, V., Rocchi, C., Motta, C., Lauretti, B., Perugini, J., Brambilla, L., and Centonze, D. (2017). Heart rate variability is diferentially altered in multiple sclerosis: Implications for acute. worsening and progressive disability. Mult. Scler. J. Exp. Transl. Clin., 3.","DOI":"10.1177\/2055217317701317"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1177\/1352458507078399","article-title":"Vagal nerve stimulation improves cerebellar tremor and dysphagia in multiple sclerosis","volume":"13","author":"Marrosu","year":"2007","journal-title":"Mult. Scler."},{"key":"ref_54","first-page":"22","article-title":"Mindful Breathing Offers Relief for Myasthenia Gravis: A Case Report","volume":"33","author":"Kass","year":"2019","journal-title":"Adv. Mind Body Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/S0161-4754(03)00072-1","article-title":"Chiropractic care of a pediatric patient with myasthenia gravis","volume":"26","author":"Alcantara","year":"2003","journal-title":"J. Manip. Physiol. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0161-4754(99)70066-7","article-title":"Chiropractic management of a patient with myasthenia gravis and vertebral subluxations","volume":"22","author":"Alcantara","year":"1999","journal-title":"J. Manip. Physiol. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.brs.2017.05.006","article-title":"Non-invasive vagus nerve stimulation acutely improves spontaneous cardiac baroreflex sensitivity in healthy young men: A randomized placebo-controlled trial","volume":"10","author":"Antonino","year":"2017","journal-title":"Brain Stimul."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/10\/2173\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:03:05Z","timestamp":1760162585000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/10\/2173"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,18]]},"references-count":57,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["jcm10102173"],"URL":"https:\/\/doi.org\/10.3390\/jcm10102173","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,18]]}}}