Paroxysmal and unusual symptoms as first clinical manifestation of multiple sclerosis do not indicate benign prognosis—The PaSiMS II study

PLOS ONE, Dec 2019

Background Paroxysmal (PS) and unusual symptoms (US) account for approximately 1.6% of initial manifestations of multiple sclerosis (MS) and have comparable conversion rates to clinically definite MS (CDMS) as classical bout onset symptoms (CS). However, long-term prognosis and clinical outcome of patients experiencing PS or US as first clinical manifestation are unclear. Methods Clinical, MRI and cerebrospinal fluid data were obtained retrospectively and patients presenting with PS or US were compared to patients with CS presentation. Results In a cohort of 532 relapsing onset MS patients followed for a mean period of 11.4 years (SD 3.6), 10 (1.9%) patients initially presented with PS/US. PS/US patients received disease modifying treatment (DMT) in a significantly smaller proportion immediately after the first clinical symptom (30% vs. 61.7%; p = 0.021) and during the observation period (60% vs. 83.5%; p = 0.033). In multivariate models correcting for sex, age at initial symptoms, complete remission of initial symptoms, total number of T2 and contrast-enhancing lesions, presence of oligoclonal bands and DMT exposure, PS/US were not associated with lower annualized relapse rate or lower EDSS over time. Conclusion In addition to a similar conversion rate to CDMS, patients presenting with PS/US at disease onset display very similar relapse and disability rates as patients with CS onset. Consequently, initial presentation with PS/US does not indicate benign or atypical MS, but requires DMT initiation based on the same criteria as in CS patients.

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Paroxysmal and unusual symptoms as first clinical manifestation of multiple sclerosis do not indicate benign prognosis—The PaSiMS II study

July Paroxysmal and unusual symptoms as first clinical manifestation of multiple sclerosis do not indicate benign prognosisÐThe PaSiMS II study Gabriel Bsteh 0 1 Rainer Ehling 0 1 Lisa-Maria Walchhofer 0 Harald Hegen 0 1 Michael Auer 0 1 Sebastian Wurth 0 1 Franziska Di Pauli 0 1 Michaela Wagner 0 Markus Reindl 0 1 Florian Deisenhammer 0 1 Thomas Berger 0 1 ☯ These authors contributed equally to this work. 0 0 0 Editor: Sreeram V. Ramagopalan, University of Oxford , UNITED KINGDOM 1 Department of Neurology, Medical University of Innsbruck , Innsbruck , Austria , 2 Department of Neurology, Clinic for Rehabilitation Muenster , Muenster , Austria , 3 Department of Neuroradiology, Medical University of Innsbruck , Innsbruck , Austria - annualized relapse rate or lower EDSS over time. Conclusion In addition to a similar conversion rate to CDMS, patients presenting with PS/US at disease onset display very similar relapse and disability rates as patients with CS onset. a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Competing interests: Markus Reindl is an academic editor for PLOS ONE. We declare the following conflicts of interest. GB has participated in meetings sponsored by Biogen, Merck Serono, Background unclear. Methods Results Novartis, Genzyme and Teva Ratiopharm. RE has participated in meetings sponsored by and received honoraria (lectures and consultations) from Biogen, Merck Serono and Teva Ratiopharm, has received grants for educational purposes from Biogen, BoÈhringer Ingelheim, Merck Serono, Novartis Pharma GmbH, Ottobock and Teva Ratiopharm, and has received honoraria for acting as consultant for Teva Pharmaceuticals Europe. LMW has participated in meetings sponsored by Bayer and Stryker. HH has participated in meetings sponsored by, received speaker honoraria or travel funding from Bayer Schering, Biogen, Merck Serono and Novartis, and received honoraria for acting as consultant for Teva Pharmaceuticals Europe. MA received speaker honoraria from Novartis. SW has participated in meetings sponsored by, received honoraria or travel funding from Biogen, Merck Serono, Novartis, Sanofi Genzyme, Teva Ratiopharm, Allergan, Ipsen Pharma and Roche. FDP has received speaking honoraria from Biogen-Idec and Sanofi-Aventis Austria. MW reports no conflict of interest. MR reports no conflict of interest. FD has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Bayer Healthcare, Biogen, Genzyme-Sanofi, Merck, Novartis Pharma, Roche and TEVA. TB has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for MS: Bayer, Biogen, Genzyme, Merck, Novartis, Octapharma, Ratiopharm, Roche, Sanofi Aventis, TEVA. His institution has received financial support in the past 12 months by unrestricted research grants (Biogen, Bayer, Merck, Novartis, Ratiopharm, Sanofi Aventis) and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, Merck, Novartis, Octapharma, Roche, Sanofi Aventis, TEVA. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Consequently, initial presentation with PS/US does not indicate benign or atypical MS, but requires DMT initiation based on the same criteria as in CS patients. 1. Introduction Paroxysmal symptoms (PS) are brief (lasting seconds to minutes) symptoms occurring suddenly and many times a day. They are often stereotyped and continue in clusters with great intensity for days up to a few months[1]. While their pathophysiology is well characterised, they are among the most frequently misinterpreted manifestations of multiple sclerosis (MS) (1). Since the latest revision of the definition of a MS relapse, PS (historical or current) are now accepted as relapses as long as they consist of multiple episodes occurring over not less than 24 hours [2]. ªUnusual symptomsº (US) are thought to represent the clinical correlate of mainly cortical MS lesions [3,4]. Most frequently, focal epileptic seizures and various types of aphasia are classified as US in MS [1]. In a previous large scale study, Paroxysmal and Unusual Symptoms in MS (PaSiMS I), we found a prevalence rate of 1.1% and 0.5% for PS and US as initial manifestation of MS, respectively [5]. Prediction of long-term prognosis at disease onset is generally challenging in MS. Female sex, young age, complete remission of initial symptoms, absence of oligoclonal bands (OCB), low T2 lesion load and absence of contrast-enhancing (CE) lesions have consistently been identified as predictive factors for favourable long-term outcome [6±12]. Recently, we have demons (...truncated)


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Gabriel Bsteh, Rainer Ehling, Lisa-Maria Walchhofer, Harald Hegen, Michael Auer, Sebastian Wurth, Franziska Di Pauli, Michaela Wagner, Markus Reindl, Florian Deisenhammer, Thomas Berger. Paroxysmal and unusual symptoms as first clinical manifestation of multiple sclerosis do not indicate benign prognosis—The PaSiMS II study, PLOS ONE, 2017, Volume 12, Issue 7, DOI: 10.1371/journal.pone.0181458