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DI-017 Mefloquine in progressive multifocal leukoencephalopathy
  1. P Nieto Guindo1,
  2. FD Fernandez-Gines2,
  3. E Molina Cuadrado2,
  4. I Alferez Garcia2
  1. 1CH Torrecardenas, Almeria, Spain
  2. 2CH Torrecardenas, Hospital Pharmacy, Almeria, Spain

Abstract

Background Natalizumab 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.

Purpose To analyse the efficacy and safety of mefloquine in a case of natalizumab related PML.

Material and methods A 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.

Results Efficacy: 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.

Conclusion Despite 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.

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