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      Postural Orthostatic Tachycardia Predicts Early Conversion to Multiple Sclerosis after Clinically Isolated Syndrome

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          Abstract

          Background/Aims: There have been suggestions that interactions exist between the autonomic nervous system (ANS) and the immune system functions in multiple sclerosis (MS). We aimed to evaluate the ANS dysfunction, more specifically postural orthostatic tachycardia syndrome (POTS), as a possible predictor of conversion to MS in patients with clinically isolated syndrome (CIS). Methods: In this observational, prospective, longitudinal study, 84 patients were enrolled (56 females, mean age 32.9 ± 8.9 years). Disease activity during a 6-month period was monitored (relapses and/or MRI disease activity indicated by new T2 or T1 enhancing lesions), and the following predictors analyzed: age, Expanded Disability Status Scale, MRI midbrain, pontine or medulla oblongata lesions, and POTS on the head up tilt test. Results: POTS was identified in 8 (9.5%) patients. Of 84 patients, 62 (73.8%) completed the 6-month follow-up, and 28 (45.2%) patients converted to MS. Results of the multivariate regression analysis revealed age (10-year increase) and POTS as significant predictors of early conversion to MS (OR 2.34, 95% CI 1.15-4.78, p = 0.019 and OR 12.40, 95% CI 1.13-136.62, p = 0.040). The logistic model was statistically significant, χ<sup>2</sup> (6) = 13.885, p = 0.031. Conclusion: POTS may be an indicator of a more active disease course in CIS patients and possibly be used as a prognostic factor.

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          Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome.

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            Autoimmune Basis for Postural Tachycardia Syndrome

            Background Patients with postural tachycardia syndrome (POTS) have exaggerated orthostatic tachycardia often following a viral illness, suggesting autoimmunity may play a pathophysiological role in POTS. We tested the hypothesis that they harbor functional autoantibodies to adrenergic receptors (AR). Methods and Results Fourteen POTS patients (7 each from 2 institutions) and 10 healthy subjects were examined for α1AR autoantibody‐mediated contractility using a perfused rat cremaster arteriole assay. A receptor‐transfected cell‐based assay was used to detect the presence of β1AR and β2AR autoantibodies. Data were normalized and expressed as a percentage of baseline. The sera of all 14 POTS patients demonstrated significant arteriolar contractile activity (69±3% compared to 91±1% of baseline for healthy controls, P<0.001) when coexisting β2AR dilative activity was blocked; and this was suppressed by α1AR blockade with prazosin. POTS sera acted as a partial α1AR antagonist significantly shifting phenylephrine contractility curves to the right. All POTS sera increased β1AR activation (130±3% of baseline, P<0.01) and a subset had increased β2AR activity versus healthy subjects. POTS sera shifted isoproterenol cAMP response curves to the left, consistent with enhanced β1AR and β2AR agonist activity. Autoantibody‐positive POTS sera demonstrated specific binding to β1AR, β2AR, and α1AR in transfected cells. Conclusions POTS patients have elevated α1AR autoantibodies exerting a partial peripheral antagonist effect resulting in a compensatory sympathoneural activation of α1AR for vasoconstriction and concurrent βAR‐mediated tachycardia. Coexisting β1AR and β2AR agonistic autoantibodies facilitate this tachycardia. These findings may explain the increased standing plasma norepinephrine and excessive tachycardia observed in many POTS patients.
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              Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study.

              We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort.
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                Author and article information

                Journal
                ENE
                Eur Neurol
                10.1159/issn.0014-3022
                European Neurology
                S. Karger AG
                0014-3022
                1421-9913
                2017
                June 2017
                05 April 2017
                : 77
                : 5-6
                : 253-257
                Affiliations
                aSchool of Medicine, University of Zagreb, and bUniversity Hospital Center Zagreb, Department of Neurology, Referral Center for Autonomic Nervous System Disorders, Zagreb, Croatia
                Author notes
                *Mario Habek, MD, PhD, University Department of Neurology, University Hospital Center Zagreb, Kišpatićeva 12, HR-10000 Zagreb (Croatia), E-Mail mhabek@mef.hr
                Author information
                https://orcid.org/0000-0002-3360-1748
                Article
                469707 Eur Neurol 2017;77:253-257
                10.1159/000469707
                28376495
                7e60ff93-d6cd-4d14-96d0-0ae15411b178
                © 2017 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 05 January 2017
                : 07 March 2017
                Page count
                Figures: 1, Tables: 3, References: 13, Pages: 5
                Categories
                Original Paper

                Geriatric medicine,Neurology,Cardiovascular Medicine,Neurosciences,Clinical Psychology & Psychiatry,Public health
                Postural orthostatic tachycardia syndrome,Clinically isolated syndrome,Multiple sclerosis,Autonomic nervous system

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