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Open AccessCase Report

Fulminant MS Reactivation Following Combined Fingolimod Cessation and Yellow Fever Vaccination

Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, D-48149 Muenster, Germany
Institute of Neuropathology, University Hospital Muenster, D-48149 Muenster, Germany
Bernhard Nocht Institute for Tropical Medicine, WHO Collaborating Centre for Arbovirus and Hemorrhagic Fever Reference and Research, D-20359 Hamburg, Germany
Faculty of Mathematics, Informatics and Natural Sciences, University of Hamburg, D-20146 Hamburg, Germany
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(23), 5985;
Received: 12 November 2019 / Revised: 24 November 2019 / Accepted: 26 November 2019 / Published: 28 November 2019
(This article belongs to the Special Issue CNS Drug Action in Neurodegenerative Diseases)
A major concern caused by the discontinuation of disease modifying treatment for multiple sclerosis (MS) is a rebound of disease activity. Hypotheses about the underlying mechanism of fingolimod (FTY) induced exaggerated inflammatory responses are diverse. So far, vaccinations as a trigger for rebound activity following FTY suspension have not been described. However, several reports have highlighted the occurrence of neurological and autoimmune side effects after single or combined multi-vaccination procedures. Here, we describe the case of a highly active female MS patient demonstrating recurrent, severe MS relapses accompanied by extensive MRI activity, subsequent to yellow fever vaccination two months following FTY withdrawal. Blood and cerebrospinal fluid immunophenotyping indicated a B cell/plasma cell autoreactivity. Following a therapy with natalizumab the clinical, laboratory, MRI, and disease course improved significantly. This case hints towards a combined immunological mechanism characterized by molecular mimicry, bystander activation, and lymphocyte re-egress, resulting in extensive neurological impairment and shows that natalizumab represents a therapeutic option to counteract B cell mediated autoreactivity. Especially, the diagnostic and therapeutic management of this complex scenario might be instructive for clinical practice. View Full-Text
Keywords: fingolimod; multiple sclerosis; vaccination; yellow fever; autoimmune disease fingolimod; multiple sclerosis; vaccination; yellow fever; autoimmune disease
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Rolfes, L.; Pawlitzki, M.; Pfeuffer, S.; Thomas, C.; Schmidt-Chanasit, J.; Gross, C.C.; Schulte-Mecklenbeck, A.; Wiendl, H.; Meuth, S.G.; M. Grauer, O.; Ruck, T. Fulminant MS Reactivation Following Combined Fingolimod Cessation and Yellow Fever Vaccination. Int. J. Mol. Sci. 2019, 20, 5985.

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