Natalizumab-associated PML identified in the presymptomatic phase using MRI surveillance

Abstract

Natalizumab, a humanized monoclonal antibody that binds to the cellular adhesion molecule α4-integrin, prevents leukocytes from crossing the blood–brain barrier. It is effective in multiple sclerosis (MS), but its use is limited by the potential risk of progressive multifocal leukoencephalopathy (PML). ### Case report. A 61-year-old woman with a 7-year history of relapsing-remitting MS developed PML after treatment with natalizumab for 24 months. Past history included breast cancer 13 years prior, treated with lumpectomy, radiotherapy, and chemotherapy, followed by tamoxifen. Her MS was initially treated with interferon-β over 5 years, during which time her disease developed a relapsing-remitting course, with 2 significant clinical relapses. Additionally, she developed clinically asymptomatic demyelinating lesions on cerebral MRI. Interferon-β was stopped and monthly methylprednisolone was given for 3 months. Her disease remained refractory to treatment and 2 years ago she was commenced on natalizumab. She underwent 6-monthly clinical and radiologic reviews with MRI. There was mild worsening of lower limb spasticity and ataxia over 2 years but no major relapses. MRI at 6, 12, and 18 months showed no new lesions. Routine MRI at 24 months after commencement of natalizumab showed a region of juxtacortical white matter fluid-attenuated …