<p>Progressive Multifocal Leukoencephalopathy: Current Insights</p>

Abstract

Cases of PML should be evaluated according to predisposing factors, as these subgroups differ by incidence rate, clinical course, and prognosis. The three most significant groups at risk of PML are patients with hematological malignancies mostly previously treated with immunotherapies but also untreated, patients with HIV infection, and patients using monoclonal antibody (mAb) treatments. Epidemiological data is scarce and partly conflicting, but the distribution of the subgroups appears to have changed. While there is no specific anti-JCPyV treatment, restoration of the immune function is the most effective approach to PML treatment. Research is warranted to determine whether immune checkpoint inhibitors could benefit certain PML subgroups. There are no systematic national or international records of PML diagnoses or a risk stratification algorithm, except for MS patients receiving natalizumab (NTZ). These are needed to improve PML risk assessment and to tailor better prevention strategies.

Fifty Years of JC Polyomavirus: A Brief Overview and Remaining Questions

“…As such, other classifications of PML are exceedingly rare [58,59]. The prevalence of PML worldwide is often estimated to be about two cases per 100,000 individuals, though this number varies by population [47,60].…”

Natalizumab-associated progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS): “a case report from Ireland with review of literature, clinical pitfalls and future direction”

“…PML is a serious demyelinating disorder that is caused by John Cunningham virus (JCV) due to its reactivation in certain immune states in different disease conditions. It is exclusively a disease of immunosuppressed individuals, and various associations include malignancy, HIV infection, organ transplantation, and autoimmune disorders [1][2][3].…”

“…The latent virus usually stays in the kidneys and lymphoid organs, but cellular immunosuppression can cause its reactivation. Viral replication under immunomodulation leads to production of neurotropic variants that can replicate in glial cells [1].…”

Viral Genomic Characterization and Replication Pattern of Human Polyomaviruses in Kidney Transplant Recipients

“…To date, the most relevant HPyVs detected in this particular group of patients are BK Polyomavirus (BKPyV), JC Polyomavirus (JCPyV), and Merkel Cell Polyomavirus (MCPyV) [ 2 , 4 , 5 ]. In particular, BKPyV has been linked to Polyomavirus-associated nephropathy (PVAN), JCPyV to progressive multifocal leukoencephalopathy (PML), and MCPyV to some forms of non-melanoma skin cancer [ 6 ]. Whether such complications are actually caused by reactivations of latent viruses of the recipient or rather by viruses transmitted by the donor through the allograft remains unclear [ 5 ].…”