Abstract

Multiple Sclerosis is associated with an increased risk of infections. This increased risk is driven by the disability caused by MS and the disease modifying drugs (DMD) that are used to treat MS.

This teaching course is designed to inform the practitioner about infection risks with multiple sclerosis disease modifying drugs. The content will address the immune dysregulation occasioned by each class of DMTs and the anticipated infections occurring as a consequence, the current state of knowledge with respect to the observed risk of infection with each class of agent, and risk mitigation strategies. Various disease states will be described to improve the practitioner’s ability for early detection. Special attention will be afforded to progressive multifocal leukoencephalopathy, cryptococcal meningitis, and infection risks with B cell depleting agents. Additionally, the effect of DMTs on COVID morbidity and mortality will also be discussed.

The participants will learn about infectious risks associated with different DMDs, how to diagnose them and how to mitigate these infectious risks.

Abstract

Progressive multifocal leukoencephalopathy (PML) is caused by JC virus (JCV) infection of the central nervous system. PML and other JC virus-associated neurological disorders usually occur in the setting of systemic immunodeficiency caused by other infections (e.g., HIV/AIDS), cancer and immunosuppressive therapies. Several multiple sclerosis-associated DMTs are implicated in the development of PML. PML clinical outcomes depend on both the underlying susceptibility as well as the extent and anatomic location of PML lesions. Monitoring the risk for PML is an evolving area that includes JCV serology and PCR detection as well as neuroimaging. Essential diagnostic tools for PML include neuroimaging and CSF JC virus detection although brain biopsy remains in use. Neurological immune reconstitution inflammatory syndrome (NeuroIRIS) can complicate immune restoration during PML. Therapy for PML is limited although targeting immune checkpoint inhibitors is a promising approach.