Predictors of severity and functional outcome in natalizumab-associated progressive multifocal leukoencephalopathy.
Progressive multifocal leukoencephalopathy (PML) is an emerging complication of immunosuppressive therapies, especially natalizumab in multiple sclerosis (MS). Factors associated with functional outcome of natalizumab-associated PML (natalizumab-PML) have not been sufficiently described.



We retrospectively analyzed medical records of all patients with natalizumab-PML ( n = 32) treated in our hospital since 2009. Disability measured by Expanded Disability Status Scale (EDSS) at two different time points (highest available EDSS during PML and last available EDSS after PML diagnosis) served as functional outcome parameters. Clinical, laboratory, and imaging data were analyzed for association with functional outcome by applying Spearman's rho and multivariate regression analysis.



In all, 31/32 patients survived PML. A poor functional outcome was associated with higher age, higher initial John Cunningham virus (JCV) copy number in cerebrospinal fluid (CSF), and more extensive PML lesions on initial magnetic resonance imaging (MRI). No association between functional outcome and the duration of natalizumab therapy or a delayed PML diagnosis was observed.



This study will be useful for neurological practice to estimate functional outcome or disease severity of natalizumab-PML in primary care settings.
Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
Robert
R
Hoepner
Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
Eva M
EM
Kolb
Department of Neurology, Alfried Krupp Hospital, Essen, Germany.
Stefanie
S
Dahlhaus
Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
Kerstin
K
Hellwig
Department of Virology, Heinrich Heine University, Düsseldorf, Germany.
Ortwin
O
Adams
Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
Ingo
I
Kleiter
Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany/Department of Neurology, University Hospital Bern and University of Bern, Bern, Switzerland.
Anke
A
Salmen
Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
Ruth
R
Schneider
Department of Radiology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
Carsten
C
Lukas
Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany/Department of Neurology, University Hospital Bern and University of Bern, Bern, Switzerland.
Andrew
A
Chan
Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
Joseph R
JR
Berger
Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
Ralf
R
Gold
D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000175:diagnosis* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy*; D000069442:Natalizumab / Q000009:adverse effects*; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index
D007155:Immunologic Factors; D000069442:Natalizumab
Expanded Disability Status Scale; John Cunningham Virus; Tysabri; long-term follow-up; multiple sclerosis; very late antigen-4