ReviewProgressive multifocal leukoencephalopathy and JC Virus-related disease in modern neurology practice

- Natalizumab-associated JCV reactivation can cause both PML and possibly JCV granule cell neuronopathy.
- Natalizumab acts in several ways to increases PML risk.
- There are limitations in our understanding of PML risk, particularly in the JCV seronegative population.
- Imaging features can help distinguish MS PML and PML-IRIS.
- The goal of therapy in PML is reinstatement of immunocompetence.

The natural history and clinical import of Progressive Multifocal Leukoencephalopathy has changed enormously in the last thirty years. After a resurgence of PML during the HIV/AIDS epidemic, advances in the treatment of multiple sclerosis created another group of 'at risk' patients. With a focus on issues pertaining to the multiple sclerosis patient population, this review covers pathophysiology of the JC virus, causes of PML, mechanisms by which natalizumab increases the risk of PML, determinants of PML risk in natalizumab-treated patients, risks of natalizumab discontinuation, PML prevention and surveillance, PML imaging features, PML diagnosis and stumbling blocks to making the diagnosis, PML and PML-Immune Reconstitution Inflammatory Syndrome (IRIS) treatment.