Advances in Treatment of Progressive Multifocal Leukoencephalopathy

Abstract

Progressive multifocal encephalopathy (PML) is a severe demyelinating disease of the central nervous system (CNS) caused by JC virus (JCV), which occurs in immunocompromised individuals. Management of PML relies on restoration of immunity within the CNS. However, when this restoration cannot be readily achieved, PML has a grim prognosis. Innovative strategies have shown promise in promoting anti‐JCV immune responses, and include T‐cell adoptive transfer or immune checkpoint inhibitor therapies. Conversely, management of immune reconstitution inflammatory syndrome, particularly in iatrogenic PML, remains a major challenge. In this paper, we review recent development in the treatment of PML. ANN NEUROL 2021;90:865–873

Natalizumab extended-interval dosing in multiple sclerosis to mitigate progressive multifocal leukoencephalopathy risk: initial study evidence and real-world experience

“… 13 , 14 PML is strongly associated with, although not limited to, immunosuppressed status and predominantly occurs in individuals with acquired immunodeficiency syndrome (AIDS). 15 A pooled analysis of 4 large, observational, open-label studies provided valuable insights into PML risk associated with natalizumab treatment. 16 In JCV antibody-positive pwMS with previous immunosuppressant use, the estimated cumulative PML probability over 6 years is 2.7% (95% Confidence Interval (CI) 1.8-4.0), and 1.7% (95% CI 1.4-2.1) in those without this pre-treatment.…”

A Case of Progressive Multifocal Leukoencephalopathy in a Child with Hyper-Immunoglobulin M Syndrome: The Impact of Missed Care during the COVID-19 Pandemic

“…Common clinical presentations include insidious cognitive dysfunction, aphasia, motor or sensory dysfunction, and coordination and gait difficulties [1,7,8]. Brain MRI of PML typically shows multiple hyperintense lesions on T2-weighted images and the fluid-attenuated inversion recovery sequence in the affected white matter with or without gadolinium enhancement.…”

“…The introduction of antiretroviral therapy significantly improved the outcomes of HIV-related PML patients. In immunomodulatory drug-induced PML, the discontinuation of these drugs can be considered to improve the patient's outcome [7]. Therefore, a poor prognosis is anticipated when immune reconstitution is not feasible [7].…”

“…In immunomodulatory drug-induced PML, the discontinuation of these drugs can be considered to improve the patient's outcome [7]. Therefore, a poor prognosis is anticipated when immune reconstitution is not feasible [7]. In the past few decades, several antiviral therapies, including cidofovir for treating JCV, have been investigated with poor results [1].…”

“…Nevertheless, several clinical trials could not show decreased mortality in PML patients treated with cytarabine [1]. JCV-specific therapy to improve cellular immunity, including anti-programmed death-1 (anti-PD-1) antibodies (nivolumab and pembrolizumab) and interleukins, have also been tested over the past few years [7]. However, evaluations are limited to case reports or case series.…”