title: Lessons learned from fatal progressive multifocal leukoencephalopathy in a patient with multiple sclerosis treated with natalizumab.
abstract: OBJECTIVE
  To describe the clinical, radiological, and histopathological features of a fatal case of progressive multifocal leukoencephalopathy (PML) in a patient with multiple sclerosis treated with natalizumab. We will use this case to review PML risk stratification and diagnosis.
  
  
  METHODS
  Case report.
  
  
  METHODS
  Tertiary referral center hospitalized care.
  
  
  METHODS
  A 55-year-old, JC virus (JCV) antibody-positive patient with multiple sclerosis who died of PML after receiving 45 infusions of natalizumab.
  
  
  METHODS
  Brain magnetic resonance imaging and cerebrospinal fluid JCV DNA polymerase chain reaction results.
  
  
  RESULTS
  The patient developed subacute onset of bilateral blindness following his 44th dose of natalizumab. Ophthalmologic examination was normal, the brain magnetic resonance imaging was not suggestive of PML, and cerebrospinal fluid analysis did not reveal the presence of JCV DNA. The patient was subsequently treated for a presumed multiple sclerosis relapse with high-dose corticosteroids. Two weeks after his 45th dose of natalizumab, he developed hemiplegia that evolved into quadriparesis. Repeated magnetic resonance imaging and cerebrospinal fluid studies were diagnostic for PML. Postmortem histopathological analysis demonstrated PML-associated white matter and cortical demyelination.
  
  
  CONCLUSIONS
  The risks and benefits of natalizumab must be reassessed with continued therapy duration. When there is high clinical suspicion for PML in the setting of negative test results, close clinical vigilance is indicated, natalizumab treatment should be suspended, and JCV polymerase chain reaction testing and brain magnetic resonance imaging scans should be repeated.
authors: Departments of Neurology and Neuroscience, The Ohio State University, 460 W 12th Ave, Columbus, OH 43210 , USA.
authors: Aaron L
authors: AL
authors: Boster
authors: Jacqueline A
authors: JA
authors: Nicholas
authors: Ilir
authors: I
authors: Topalli
authors: Yaz Y
authors: YY
authors: Kisanuki
authors: Wei
authors: W
authors: Pei
authors: Bethanie
authors: B
authors: Morgan-Followell
authors: Claudia F
authors: CF
authors: Kirsch
authors: Michael K
authors: MK
authors: Racke
authors: David
authors: D
authors: Pitt
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D017809:Fatal Outcome; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy*; D000069442:Natalizumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab