Editors’ Welcome: Pregnancy and progressive multifocal leukoencephalopathy

Abstract

Concerns about the risk of progressive multifocal leukoencephalopathy (PML) caused by the John Cunningham (JC) virus are foremost in the minds of neurologists who manage patients with multiple sclerosis (MS). Prior to the introduction of natalizumab in 2007, only sporadic cases of MS-PML were observed. They had been treated previously with strong immune suppressant medications like cyclophosphamide ( Tan et al., 2011 Tan I.L. Koralnik I.J. Rumbaugh J.A. Burger P.C. King-Rennie A. McArthur J.C. Progressive multifocal leukoencephalopathy in a patient without immunodeficiency. Neurology. 2011; 77: 297-299 Crossref PubMed Scopus (19) Google Scholar ). Since 2007, the number of cases of MS-PML has topped 700, mostly related to the worldwide use of natalizumab, but also reflecting a handful of patients using popular medications including rituximab ( Bohra et al., 2017 Bohra C. Sokol L. Dalia S. Progressive Multifocal Leukoencephalopathy and Monoclonal Antibodies: A Review. Cancer Control. 2017; 24 (1073274817729901) Crossref PubMed Scopus (50) Google Scholar ), fingolimod ( Yoshii et al., 2017 Yoshii F. Moriya Y. Ohnuki T. Ryo M. Takahashi W. Neurological safety of fingolimod: An updated review. Clin Exp Neuroimmunol. 2017; 8: 233-243 Crossref PubMed Scopus (38) Google Scholar ), and dimethyl fumarate ( Gieselbach et al., 2017 Gieselbach R.J. Muller-Hansma A.H. Wijburg M.T. de Bruin-Weller M.S. van Oosten B.W. Nieuwkamp D.J. Coenjaerts F.E. Wattjes M.P. Murk J.L. Progressive multifocal leukoencephalopathy in patients treated with fumaric acid esters: a review of 19 cases. J Neurol. 2017; 264: 1155-1164 Crossref PubMed Scopus (56) Google Scholar ). After six years of careful study, the four strongest risk factors that predict PML in the MS population are 1. Use of prior immune suppressive medications, 2. Exposure and immune response to the JC virus, 3. Duration of treatment with natalizumab ( Biogen, 2017 Biogen , 2017 . TYSABRI® (natalizumab): PML Incidence in Patients Receiving TYSABRI. Biogen. Google Scholar ) and 4. Age. It is difficult to tease out the risk of PML posed by any individual treatment because most MS patients with PML have been on multiple medications. The calculated incidence of PML from natalizumab has now increased to 13 per 1,000 among those with seropositive JC virus antibody titers and prior immune suppressive exposure ( Biogen, 2017 Biogen , 2017 . TYSABRI® (natalizumab): PML Incidence in Patients Receiving TYSABRI. Biogen. Google Scholar ).