title: Immune-reconstitution Inflammatory Syndrome in Multiple Sclerosis Patients Treated With Natalizumab: A Series of 4 Cases.
abstract: OBJECTIVE
  Natalizumab (NTZ) is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). Progressive multifocal leukoencephalopathy (PML) is a rare complication of NTZ treatment. In patients developing PML, NTZ cessation causes a reconstruction of cellular immunity, a rapid transition of cells through the blood-brain barrier, and significant inflammation in the central nervous system, leading to immune-reconstitution inflammatory syndrome (IRIS), with potentially poor outcomes. The occurrence of this syndrome is accelerated by plasmapheresis, the standard treatment for NTZ-PML, due to enhanced clearance of NTZ and thus rapid reconstitution of cellular immunity. IRIS can also occur after cessation of NTZ in the absence of PML.
  
  
  METHODS
  We describe 4 patients who developed IRIS after NTZ cessation.
  
  
  RESULTS
  For the first patient, treatment was switched to fingolimod to avoid risk of developing PML. Despite plasmapheresis, corticosteroids, and other therapies, the outcome in this patient was fatal. For the 3 other patients, PML was detected early on magnetic resonance imaging, and IRIS after NTZ cessation was managed with a favorable outcome; 1 of these patients was managed without plasmapheresis or corticosteroid treatment.
  
  
  CONCLUSIONS
  These cases demonstrate the need to consider and manage therapeutic strategies relative to the individual patient's risk for PML or IRIS. NTZ cessation to avoid PML risk can lead to severe IRIS without PML. On the other hand, if PML develops and is detected early, plasmapheresis may not be considered necessary and IRIS may be limited, with a favorable outcome. These 2 scenarios should be considered when managing NTZ MS patients.
authors: Neuroimmunology Unit, Neurology Service, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors: Rosy
authors: R
authors: N'gbo N'gbo Ikazabo
authors: Neuroimmunology Unit, Neurology Service, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors: Christian
authors: C
authors: Mostosi
authors: Centre Hospitalier de Jolimont-Lobbes, Lobbes, Belgium.
authors: Bénédicte
authors: B
authors: Quivron
authors: Centre Hospitalier de Wallonie picarde, Site Union, Tournai, Belgium.
authors: Xavier
authors: X
authors: Delberghe
authors: Neuroimmunology Unit, Neurology Service, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors: Kaoutar
authors: K
authors: El Hafsi
authors: Neuroimmunology Unit, Neurology Service, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: andreas.lysandropoulos@erasme.ulb.ac.be.
authors: Andreas P
authors: AP
authors: Lysandropoulos
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000139:chemically induced*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy; D000069442:Natalizumab / Q000008:administration & dosage / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab
keywords: JC virus; immune-reconstitution inflammatory syndrome; multiple sclerosis; natalizumab; progressive multifocal leukoencephalopathy