DI-017 Mefloquine in progressive multifocal leukoencephalopathy

Abstract

BackgroundNatalizumab increases the risk of progressive multifocal leukoencephalopathy (PML), a potentially lethal brain disorder caused by JC polyomavirus (JCV). The antimalarial mefloquine has shown activity against JCV in vitro, but little evidence supports its use in vivo.PurposeTo analyse the efficacy and safety of mefloquine in a case of natalizumab related PML.Material and methodsA 51-year-old Caucasian woman was admitted to the emergency department in March 2013 complaining of ongoing limb weakness and slurred speech. Relevant past medical and drug history: relapsing remitting multiple sclerosis diagnosed in 2004, receiving monthly natalizumab since July 2010 (last infusion 4 days previously). High dose corticoid therapy plus supporting measures were started immediately. 10 days after admission, PML infection was confirmed based on contrast enhanced MRI findings and positive CRP for JCV DNA in cerebrospinal fluid. Patient consent and institutional ethics committee approval were obtained and a trial of mefloquine (250 mg for 3 days, and then 250 mg weekly) plus plasmapheresis (to accelerate removal of the antibody) were initiated.ResultsEfficacy: the patient experienced progressive motor and cognitive impairment. MRI on days 15 and 30 revealed further demyelination with areas extending into the deep white matter and the splenium of the corpus callosum. The patient died on day 55. Safety: on day 45, the patient had seizures that were treated with levetiracetam 1 g twice daily.ConclusionDespite mefloquine therapy, clinical and radiological progression was observed. Moreover, mefloquine was associated with CNS toxicity. To date, only routine MRI has ameliorated the outcome of this neuropathy at the very early stages of infection (pre-symptomatic). With the lack of firstline evidence, mefloquine has been used with mixed success in the treatment of PML although larger studies are required to assess its efficacy and safety.No conflict of interest.

Antivirals against human polyomaviruses: Leaving no stone unturned

“…High mefloquine concentrations can be reached in the brain (30-50 µM) (Table 2 and Figure 5), but the clinical efficacy of mefloquine is controversial for PML patients. 155 Two case reports involving three PML patients, 196,197 who received mefloquine monotherapy, did not show decreasing CSF JCPyV loads and no improvement of neurological symptoms. However, a PML patient achieved clearance of CSF JCPyV load after 5 months and no clinical progression within 20 months follow-up 198 (Table 3).…”