title: Disease course and outcome of 15 monocentrically treated natalizumab-associated progressive multifocal leukoencephalopathy patients.
abstract: OBJECTIVE
  Although the prognosis of natalizumab-associated progressive multifocal leukoencephalopathy (PML) seems to be better than HIV-associated PML, little is known about the long-term functional outcome in multiple sclerosis (MS) patients and the subsequent return of MS disease activity. We evaluated retrospectively 15 patients with natalizumab-associated PML treated at our centre.
  
  
  METHODS
  Fifteen MS-PML patients (nine women, six men) were referred to us from adjacent local centres. The patients had a median natalizumab exposure of 34 months at PML diagnosis. They received standardised treatment as described in previous work. Expanded Disability Status Scale (EDSS) and Karnofsky score in the year pre-PML, at PML-diagnosis (pre-immune reconstitution inflammatory syndrome (IRIS)) and post-PML were determined in 3-6 monthly intervals.
  
  
  RESULTS
  The median follow-up of these 15 patients was 21.5 months. None of the 15 patients died. Three patients had a Karnofsky score of 80 or higher, nine patients between 50-70 and three patients of 40 or lower at latest examination. Eight of the 15 patients developed seizures during acute PML phase. Fifty percent of those patients were not seizure-free one year post PML, despite continuation of antiepileptic treatment. The median EDSS in the year pre-PML was 2.5, 4.5 at PML diagnosis, 6.5 post-IRIS and 5.5 at latest examination. CSF became virus-free in eight of the 15 patients after a median time of 4.5 months. In nine patients, disease reappeared after a median time of seven months from PML diagnosis.
  
  
  CONCLUSIONS
  Although the clinical outcome of natalizumab-treated PML patients is much better than in patients with HIV-associated PML, this may be further improved by treatment at reference centres using standardised therapy regimens and transient intensive care if needed. Systematic studies of appropriate MS immunotherapies after PML are critically needed.
authors.affiliation: Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Bochum, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dahlhaus
authors.forename: Robert
authors.initials: R
authors.lastname: Hoepner
authors.forename: Andrew
authors.initials: A
authors.lastname: Chan
authors.forename: Ingo
authors.initials: I
authors.lastname: Kleiter
authors.forename: Ortwin
authors.initials: O
authors.lastname: Adams
authors.forename: Carsten
authors.initials: C
authors.lastname: Lukas
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hellwig
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000473:pathology; D003422:Critical Care; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007089:Image Enhancement; D054019:Immune Reconstitution Inflammatory Syndrome / Q000139:chemically induced / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D017567:Karnofsky Performance Status; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D000069442:Natalizumab; D012008:Recurrence; D012189:Retrospective Studies; D012640:Seizures / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy; D015996:Survival Rate
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000927:Anticonvulsants; D000069442:Natalizumab
keywords: Multiple Sclerosis; Neurovirology