Natalizumab-Related Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis: Findings from an Italian Independent Registry

• Published in: PloS one Vol. 11; no. 12; p. e0168376
• Main Authors: Prosperini, Luca, de Rossi, Nicola, Scarpazza, Cristina, Moiola, Lucia, Cosottini, Mirco, Gerevini, Simonetta, Capra, Ruggero
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.12.2016; Public Library of Science (PLoS)
• Subjects: Adult; Age; Autoimmune diseases; Biology and Life Sciences; Brain; Care and treatment; Central nervous system; Cerebrospinal fluid; Change detection; Cognitive ability; Complications and side effects; Data collection; Demographics; Deoxyribonucleic acid; Development and progression; Diagnosis; Disease-Free Survival; DNA; Drug therapy; Encephalitis; Female; Gadolinium; HIV; Human immunodeficiency virus; Humans; Immune system; Immunotherapy; JC Virus; Leukoencephalopathy; Leukoencephalopathy, Progressive Multifocal - chemically induced; Leukoencephalopathy, Progressive Multifocal - diagnostic imaging; Leukoencephalopathy, Progressive Multifocal - mortality; Leukoencephalopathy, Progressive Multifocal - physiopathology; Magnetic resonance; Magnetic Resonance Imaging; Male; Medical diagnosis; Medicine and Health Sciences; Middle Aged; Monoclonal antibodies; Multiple sclerosis; Multiple Sclerosis - diagnostic imaging; Multiple Sclerosis - drug therapy; Multiple Sclerosis - mortality; Natalizumab; Natalizumab - administration & dosage; Natalizumab - adverse effects; Neuroimaging; Neurology; NMR; Nuclear magnetic resonance; Opportunist infection; Patients; People and Places; Pictures; Polyomaviridae; Prevalence studies (Epidemiology); Progressive multifocal leukoencephalopathy; Psychiatry; Research and Analysis Methods; Restoration; Retrospective Studies; Sociodemographics; Survival; Survival Rate; Viral infections; United States > US; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0168376

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). 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. 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. 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). 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.