title: Natalizumab-Related Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis: Findings from an Italian Independent Registry.
abstract: BACKGROUND
  The monoclonal antibody natalizumab (NTZ) is a highly effective treatment for patients with multiple sclerosis (MS). However, this drug is associated with increased risk of developing Progressive Multifocal Leukoencephalopathy (PML), an opportunistic infection of central nervous system (CNS) caused by the John Cunningham polyomavirus (JCV).
  
  
  OBJECTIVE
  To describe the 12-month clinical course of 39 patients with MS (28 women, 11 men) who developed NTZ-related PML after a mean exposure of 39 infusions.
  
  
  METHODS
  An Italian independent collaborative repository initiative collected and analyzed socio-demographic, clinical, magnetic resonance imaging (MRI) data and number of JCV-DNA copies detected on cerebrospinal fluid (CSF) samples of patients diagnosed as affected by NTZ-related PML. The evolution of disability, measured by the Expanded Disability Status Scale, was assessed at NTZ start, at PML diagnosis and after 2, 6 and 12 months from PML diagnosis. The effect of clinical and paraclinical characteristics at PML diagnosis on the final outcome was also investigated.
  
  
  RESULTS
  Ten patients (25.6%) were diagnosed before 24 NTZ infusions. In six cases (15.4%) the PML suspect was made on the basis of highly suggestive MRI findings in absence of any detectable change of clinical conditions (asymptomatic PML). In patients with symptomatic PML, the diagnosis was quicker for those who presented with cognitive symptoms (n = 12) rather than for those with other neurological pictures (n = 21) (p = 0.003). Three patients (7.7%) died during the 12-month observation period, resulting in a survival rate of 92.3%. Asymptomatic PML, more localized brain involvement and gadolinium-enhancement detected at MRI, as well as lower viral load were associated with a better disability outcome (p-values<0.01).
  
  
  CONCLUSIONS
  Our findings support that early PML diagnosis, limited CNS involvement and initial signs of immune restoration are associated with a better outcome and higher survival rate, and confirm the utility of MRI as a surveillance tool for NTZ-treated patients.
authors.affiliation: Dept. of Neurology and Psychiatry, Sapienza University, Viale Dell'Università, Rome, Italy.
authors.forename: Luca
authors.identifier: http://orcid.org/0000-0003-3237-6267
authors.initials: L
authors.lastname: Prosperini
authors.affiliation: Multiple Sclerosis Centre, Spedali Civili di Brescia, Via Ciotti, Montichiari, Brescia, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: de Rossi
authors.affiliation: Multiple Sclerosis Centre, Spedali Civili di Brescia, Via Ciotti, Montichiari, Brescia, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Scarpazza
authors.affiliation: Dept. of Neurology, San Raffaele Scientific Institute, Via Olgettina, Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Moiola
authors.affiliation: Dept. of Translational Research and New Surgical and Medical Technologies, University of Pisa, Via Paradisa, Pisa, Italy.
authors.forename: Mirco
authors.initials: M
authors.lastname: Cosottini
authors.affiliation: Dept. of Neuroradiology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina, Milan, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Gerevini
authors.affiliation: Multiple Sclerosis Centre, Spedali Civili di Brescia, Via Ciotti, Montichiari, Brescia, Italy.
authors.forename: Ruggero
authors.initials: R
authors.lastname: Capra
mesh_terms: D000328:Adult; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007577:JC Virus; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000401:mortality / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality*; D000069442:Natalizumab / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D000069442:Natalizumab