title: Cryptococcal meningitis in a multiple sclerosis patient taking natalizumab.
abstract: OBJECTIVE
  Natalizumab was approved in 2004 by the US Food and Drug Administration (US-FDA) for treatment of multiple sclerosis (MS), however it was temporarily withdrawn after its use was associated with progressive multifocal leukoencephalopathy (PML). Other reported adverse events have included melanoma, primary central nervous system (CNS) lymphoma, and gastrointestinal cryptosporidiosis. An MS exacerbation may occur after discontinuation and immune reconstitution inflammatory syndrome (IRIS), particularly in the setting of PML, is also possible. We present the first case of cryptococcal meningitis in a patient taking natalizumab. Managements of both cryptococcal meningitis and MS after discontinuation of natalizumab are the focus of this report.
  
  
  METHODS
  This is a case report describing a 49-year old Caucasian man with relapsing-remitting MS (RR-MS) on natalizumab. On the twenty-fourth month of natalizumab treatment, he developed cryptococcal meningitis, prompting its discontinuation. Two months later, off natalizumab, while on antifungal treatment, he developed an MS exacerbation. Cerebrospinal fluid (CSF) JC virus polymerase chain reaction (PCR) and human immunodeficiency virus (HIV) serology were repeatedly negative.
  
  
  CONCLUSIONS
  Although specific recommendations for treating natalizumab-associated cryptococcal meningitis do not exist, our patient discontinued natalizumab and started conventional anti-fungal treatment. Two months later, he was treated with steroids due to worsening neurologic status from a presumed MS attack. Subsequently, he improved with successful treatment of the cryptococcal meningitis, with no new clinical or radiographic exacerbations.
authors.affiliation: Department of Neurology, University of Illinois College of Medicine, Illinois Neurologic Institute, Department of Medicine, Peoria, United States.
authors.forename: Reuben Mari
authors.initials: RM
authors.lastname: Valenzuela
authors.affiliation: Department of Neurology, University of Illinois College of Medicine, Illinois Neurologic Institute, Department of Medicine, Peoria, United States.
authors.forename: John H
authors.initials: JH
authors.lastname: Pula
authors.affiliation: Department of Neurology, University of Illinois College of Medicine, Illinois Neurologic Institute, Department of Medicine, Peoria, United States.
authors.forename: Dennis
authors.initials: D
authors.lastname: Garwacki
authors.affiliation: Division of Infectious Diseases, University of Illinois College of Medicine, Peoria, United States.
authors.forename: John
authors.initials: J
authors.lastname: Cotter
authors.affiliation: Department of Neurology, University of Illinois College of Medicine, Illinois Neurologic Institute, Department of Medicine, Peoria, United States. Electronic address: kattahj@uic.edu.
authors.forename: Jorge C
authors.initials: JC
authors.lastname: Kattah
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D003337:Corpus Callosum / Q000187:drug effects / Q000473:pathology; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D016919:Meningitis, Cryptococcal / Q000150:complications / Q000188:drug therapy*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000188:drug therapy*; D000069442:Natalizumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab
keywords: Cryptoccocal meningitis; Immune reconstitution inflammatory syndrome (IRIS); Multiple sclerosis (MS); Natalizumab; Progressive multifocal leukoencephalopathy (PML); Relapsing–remitting MS