Saturday, April 21, 2007

JC Virus/PML in MS

Khalili K et al. Reactivation of JC virus and development of PML in patients with multiple sclerosis. Neurology 2007;68: 985-990.
This review article of basic science issues is informative about the process of JC virus activation and infection with PML in MS patients. IN order for PML to occur, latent JC virus in kidney or lymphatic system must be activated, and disseminated to the CNS where destructive replication occurs in oligodendrocytes. Pathologically, patients with PML have the triad of demyelination, giant bizarre astrocytes and nuclear inclusions. It continues to occur in HIV patients despite HAART therapy (up to 5 % of patients prior to advent of HAART). It also is reported in leukemia, lymphoma, organ transplantation patients, after treatment of solid tumors, autoimmune disease, granulomatous disorders, agammaglobulinemia, or rarely without an associated disorder. More recently, two patients with MS and one with Crohn's d had exposure to natalizumab/other drugs and another to rituximab. HIV accounts for 80 % of cases.

JC virusAB is seen in 80 % of normals. PCR in urine is seen in 30 % of normals. Quantitative PCR (Q-PCR) can be measured in urine, serum, CSF and biopsy samples. Standardization issues and threshold issues are important. This also has been shown in the related condition, polyoma asociated nephropathy (PVN) in which screening the urine has been important. The authors hypothesize that screening the blood of patients may lessen the risk of PML. JC virus is occassionally seen in CSF of patients with MS. It is unknown if they are at risk of developing PML.

Targets for treatment include nucleoside analogues (cytarabine, cidofavir) cytokines, enzyme inhibitors, and JCV receptor blockers such as 5H2a chlorpromazine, mirtazepine, heparin, Tat inhibitors.

The authors note "Screening blood for JC viremia did not prove useful in the two MS cases and could provide a false level of security." "More MRI screening is needed."

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