Predictors of severity and functional outcome in natalizumab-associated progressive multifocal leukoencephalopathy

Abstract

Objective:

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.

Methods:

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.

Results:

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.

Conclusion:

This study will be useful for neurological practice to estimate functional outcome or disease severity of natalizumab-PML in primary care settings.

Keywords

Expanded Disability Status Scale long-term follow-up multiple sclerosis John Cunningham Virus Tysabri very late antigen-4

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References

Astrom

Mancall

Richardson

. Progressive multifocal leukoencephalopathy; a hitherto unrecognized complication of chronic lymphatic leukaemia and Hodgkin’s disease. Brain 1958; 81: 93–111.

Bellizzi

Elena

Rodio

. New insights on human polyomavirus JC and pathogenesis of progressive multifocal leukoencephalopathy. Clin Dev Immunol 2013; 2013: 839719.

Rudick

Stuart

Calabresi

. Natalizumab plus interferon beta-1a for relapsing remitting multiple sclerosis. N Engl J Med 2006; 354: 911–923.

Polman

O’Connor

Havrdova

. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354: 899–910.

Biogen Idec. Manufacture information, http://hcp.biogen-international.com/tysabri_update.aspx?ID=22076 (accessed 22 August 2016).

Vermersch

Kappos

Gold

. Clinical outcomes of natalizumab-associated progressive multifocal leukoencephalopathy. Neurology 2011; 76: 1697–1704.

Dong-Si

Gheuens

Gangadharan

. Predictors of survival and functional outcomes in natalizumab-associated progressive multifocal leukoencephalopathy. J Neurovirol 2015; 21(6): 637–644.

Wenning

Haghikia

Laubenberger

. Treatment of progressive multifocal leukoencephalopathy associated with natalizumab. N Engl J Med 2009; 361: 1075–1080.

Berger

Aksamit

Clifford

. PML diagnostic criteria: Consensus statement from the AAN neuroinfectious disease section. Neurology 2013; 80: 1430–1438.

10.

Dahlhaus

Hoepner

Chan

. Disease course and outcome of 15 monocentrically treated natalizumab-associated progressive multifocal leukoencephalopathy patients. J Neurol Neurosurg Psychiatry 2013; 84: 1068–1074.

11.

Hoepner

Ahlbrecht

Faissner

. Clinical and paraclinical findings in natalizumab-associated infratentorial progressive multifocal leukoencephalopathy patients. J Neurol Neurosurg Psychiatry 2014; 85: 1177–1178.

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