More and more multiple sclerosis patients have been receiving treatment with new immunomodulatory drugs. Its discontinuation because of side-effects, lack of efficacy or pregnancy has been increasing as well. This paper reviews such severe complications of natalizumab and fingolimod cessation as immune reconstitution inflammatory syndrome (IRIS) and rebound. The short history, immunopathogenesis and diagnostic criteria of IRIS in individuals with human immunodeficiency virus infection are covered. Clinical and radiological presentations as well as possible pathogenic mechanisms of IRIS in patients treated with natalizumab and fingolimod are discussed. The authors also report the case of a woman with multiple sclerosis treated with fingolimod, who experienced a severe relapse when she stopped treatment. Diagnostic criteria and prognostic factors for IRIS and rebound are needed in patients with multiple sclerosis who discontinue the new disease modification therapy.
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