THE EARLIER, THE SMALLER, THE BETTER FOR NATALIZUMAB-ASSOCIATED PML: IN MRI VIGILANCE VERITAS?

• Published in: Neurology Vol. 79; no. 10; pp. 1067 - 1069
• Main Authors: PHAN-BA, Rémy, BELACHEW, Shibeshih, OUTTERYCK, Olivier, MOONEN, Gustave, SINDIC, Christian, VOKAER, Mathieu, VERMERSCH, Patrick
• Format: Journal Article Web Resource
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 04-09-2012
• Subjects: Adult; Antibodies, Monoclonal, Humanized - adverse effects; Biological and medical sciences; Brain - pathology; Female; Human health sciences; Humans; Investigative techniques, diagnostic techniques (general aspects); JC virus; Leukoencephalopathy, Progressive Multifocal - chemically induced; Leukoencephalopathy, Progressive Multifocal - diagnosis; Leukoencephalopathy, Progressive Multifocal - pathology; Magnetic Resonance Imaging; Male; Medical sciences; Middle Aged; MRI; Multiple sclerosis; Natalizumab; Nervous system; Neurologie; Neurology; PML; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Sciences de la santé humaine; Vigilance; Nervous system diseases; Natalizumab; Nuclear magnetic resonance imaging
• ISSN: 0028-3878; 1526-632X; 1526-632X
• DOI: 10.1212/WNL.0b013e31826846b4

Natalizumab-associated progressive multifocal leukoencephalopathy (N-PML) in multiple sclerosis (MS) is due to CNS infection by the opportunistic JC virus (JCV). As of december 2011, 193 confirmed cases of N-PML have been observed, giving rise to an overall risk of approximately 0,202%. N-PML pathogenesis remains partially elusive although risk factors have now been clearly delineated. In patients with prior JCV infection detected by serum anti-JCV antibodies, duration of therapy and prior use of immunosuppressants (IS) increase the risk of N-PML. The clinical outcome of MS patients who developed N-PML was highly variable, ranging from asymptomatic case to varying degrees of neurological disability or even death. It was also observed in real life setting that the earlier N-PML was diagnosed and treated, the better was the clinical outcome. Clinical vigilance is now considered as the established cornerstone of PML risk-management algorithm.
Here we present early MRI features of 4 out of 8 N-PML cases, which were observed in Wallonia-Brussels and Northern France in more than 4 years of post-marketing utilization of natalizumab for both regions. We are not aware of the specific context and outcome of the 4 other N-PML cases, which were diagnosed and treated in other centers. The reported cases emphasize that (i) N-PML can have a long presymptomatic course while still being clearly detectable with MR imaging, (ii) N-PML can have a benign outcome provided it is diagnosed and treated early, (iii) a clinically symptomatic N-PML may be a further advanced infection with a poorer prognosis, and (iv) periodic brain MR scans, particularly in high risk situations, are likely to provide earlier detection of N-PML and better outcomes.