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  • Title: Lessons learned from fatal progressive multifocal leukoencephalopathy in a patient with multiple sclerosis treated with natalizumab.
    Author: Boster AL, Nicholas JA, Topalli I, Kisanuki YY, Pei W, Morgan-Followell B, Kirsch CF, Racke MK, Pitt D.
    Journal: JAMA Neurol; 2013 Mar 01; 70(3):398-402. PubMed ID: 23338729.
    Abstract:
    OBJECTIVE: To describe the clinical, radiological, and histopathological features of a fatal case of progressive multifocal leukoencephalopathy (PML) in a patient with multiple sclerosis treated with natalizumab. We will use this case to review PML risk stratification and diagnosis. DESIGN: Case report. SETTING: Tertiary referral center hospitalized care. PATIENT: A 55-year-old, JC virus (JCV) antibody-positive patient with multiple sclerosis who died of PML after receiving 45 infusions of natalizumab. MAIN OUTCOME MEASURES: Brain magnetic resonance imaging and cerebrospinal fluid JCV DNA polymerase chain reaction results. RESULTS: The patient developed subacute onset of bilateral blindness following his 44th dose of natalizumab. Ophthalmologic examination was normal, the brain magnetic resonance imaging was not suggestive of PML, and cerebrospinal fluid analysis did not reveal the presence of JCV DNA. The patient was subsequently treated for a presumed multiple sclerosis relapse with high-dose corticosteroids. Two weeks after his 45th dose of natalizumab, he developed hemiplegia that evolved into quadriparesis. Repeated magnetic resonance imaging and cerebrospinal fluid studies were diagnostic for PML. Postmortem histopathological analysis demonstrated PML-associated white matter and cortical demyelination. CONCLUSIONS: The risks and benefits of natalizumab must be reassessed with continued therapy duration. When there is high clinical suspicion for PML in the setting of negative test results, close clinical vigilance is indicated, natalizumab treatment should be suspended, and JCV polymerase chain reaction testing and brain magnetic resonance imaging scans should be repeated.
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