Irritability in a Man with Multiple Sclerosis

Abstract

Natalizumab is a highly effective therapy used for the treatment of relapsing forms of MS. However, use of the drug has been complicated by the occurrence of progressive multifocal leukoencephalopathy (PML), a disease caused by the John Cunningham (JC) virus. The risk of PML in MS is almost exclusively confined to individuals who test positive for JC virus antibody by the STRATIFY assay. Additional risk factors in JC virus antibody-positive patients include the duration of therapy and the prior use of immunosuppressive medications. Although symptoms and signs of PML can mimic those of MS, personality change, cognitive dysfunction, language disturbance, and hemiparesis are common early findings in PML. As soon as the suspicion of possible PML arises, natalizumab should be discontinued. MRI of the brain should be obtained. The appearance of any new brain lesions on MRI obtained after six months of natalizumab treatment should raise the question of PML. The diagnosis is usually confirmed by the identification of JC virus in the cerebrospinal fluid (CSF) by polymerase chain reaction. However, this test should be obtained in a laboratory that is capable of determining low copy numbers of the viral DNA. Treatment also includes plasma exchange to speed the clearance of the monoclonal antibody. Many patients develop the immune reconstitution inflammatory syndrome (IRIS) when the natalizumab is discontinued. This may entail neurological deterioration, necessitating intervention with high-dose intravenous methylprednisolone.