Abstract
BackgroundProgressive multifocal leukoencephalopathy (PML) is a rare complication associated with dimethyl fumarate (DMF) treatment for multiple sclerosis (MS). Chronic lymphopenia is considered a risk factor for DMF-associated PML. Case reportWe report a 58 year-old woman with multiple sclerosis treated with DMF who developed left-sided weakness and dysarthria, found to have acute (grade 4) on chronic (grade 3) lymphopenia in the setting of influenza infection. While symptoms and lymphocyte counts initially improved with resolution of influenza, she had subsequent clinical worsening a few weeks later. Brain MRI revealed numerous new punctate foci of gadolinium (Gd)-enhancement throughout the subcortical white matter, described as concerning for PML-immune reconstitution inflammatory syndrome (PML-IRIS). She tested positive for serum JC virus (JCV) antibodies, and cerebrospinal fluid (CSF) JCV PCR testing was positive. DMF was stopped, a brief steroid pulse was administered, and the patient has had gradual symptom improvement while maintained on glatiramer acetate. ConclusionsWhile prolonged, severe lymphopenia is a known PML risk factor with DMF, this patient's additional acute lymphopenia secondary to viral infection likely also contributed to PML development. The recovery of the acute component of lymphopenia may have contributed to development of IRIS prior to DMF discontinuation, demonstrating the importance of keeping PML in the differential diagnosis even if enhancement is seen sooner than anticipated.
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