Early detection and favourable outcome of natalizumab-related progressive multifocal leukoencephalopathy (PML) in two multiple sclerosis patients

Assessing understanding of individual risk and symptoms of progressive multifocal leukoencephalopathy in patients prescribed natalizumab for multiple sclerosis

“…Natalizumab is associated with a potentially fatal, but rare, demyelinating opportunistic brain infection, progressive multifocal leukoencephalopathy (PML). 6 Prognosis is determined by a shorter time from first symptoms to confirmed diagnosis either clinically or by magnetic resonance imaging (MRI) surveillance. [1][2][3][4] There have been 664 confirmed cases of natalizumab-associated PML to date, with a global incidence of 4.22 per 1000 patients.…”

“…5 Although asymptomatic PML patients are more likely to survive and have better long-term function, the vast majority of patients diagnosed with PML have symptoms 5 that include progressive personality changes; speech, motor, retrochiasmal visual deficits; and new seizure onset. 6 Prognosis is determined by a shorter time from first symptoms to confirmed diagnosis either clinically or by magnetic resonance imaging (MRI) surveillance. Early diagnosis, immediate cessation and removal of nataizumab results in better patient outcomes.…”

No evidence of beneficial effects of plasmapheresis in natalizumab-associated PML

“…About 84% (184 of 219 cases) of the entire NTZ-PML cohort had been treated with PLEX, while only 16% had not. The reasons why PLEX was not administered differed in each instance (e.g., long interval between PML diagnosis and NTZ withdrawal not requiring NTZ removal, 8 first occurrences as adverse events in clinical trials, 5,6 and lesion localization in eloquent areas, making the risk of PML-IRIS unjustifiable 11 ). This imbalance in treatment approach confirmed that PLEX was considered the treatment of choice for NTZ-PML in clinical practice, even if clinical trials supporting its efficacy in this population are lacking.…”

Immunological biomarkers identifying natalizumab-treated multiple sclerosis patients at risk of progressive multifocal leukoencephalopathy

“…However, at present, there is no blood biomarker of JCV activity that can be used alone to diagnose PML, and a failure to detect JCV DNA in the cerebrospinal fluid (CSF) does not rule out the possibility of having PML, particularly in the earlier stages of the disease (Brew et al, 2010;Cordioli et al, 2014). The only humoral parameter obtained routinely is the JCV seropositivity status, which is evaluated by detecting antibodies directed against JCV VP1 (the main surface JCV protein) using the single validated STRATIFY JC virus™ assay (Gorelik et al, 2010;Bozic et al, 2011;Lee et al, 2013).This assay allows neurologists to detect patients at higher risk of developing PML.…”