TY  - JOUR
AU  - Schweitzer, Finja
AU  - Laurent, Sarah
AU  - Cortese, Irene
AU  - Fink, Gereon Rudolf
AU  - Silling, Steffi
AU  - Skripuletz, Thomas
AU  - Metz, Imke
AU  - Wattjes, Mike P.
AU  - Warnke, Clemens
TI  - Progressive Multifocal Leukoencephalopathy
JO  - Neurology
VL  - 101
IS  - 16
SN  - 0028-3878
CY  - [Erscheinungsort nicht ermittelbar]
PB  - Ovid
M1  - FZJ-2023-04868
SP  - 700 - 713
PY  - 2023
AB  - JC polyomavirus (JCV) establishes an asymptomatic latent and/or persistent infection in most of the adult population. However, in immunocompromised individuals, JCV can cause a symptomatic infection of the brain, foremost progressive multifocal leukoencephalopathy (PML). In the past 2 decades, there has been increasing concern among patients and the medical community because PML was observed as an adverse event in individuals treated with modern (selective) immune suppressive treatments for various immune-mediated diseases, especially multiple sclerosis. It became evident that this devastating complication also needs to be considered beyond the patient populations historically at risk, including those with hematologic malignancies or HIV-infected individuals. We review the clinical presentation of PML, its variants, pathogenesis, and current diagnostic approaches. We further discuss the need to validate JCV-directed interventions and highlight current management strategies based on early diagnosis and restoring JCV-specific cellular immunity, which is crucial for viral clearance and survival. Finally, we discuss the importance of biomarkers for diagnosis and response to therapy, instrumental in defining sensitive study end points for successful clinical trials of curative or preventive therapeutics. Advances in understanding PML pathophysiology, host and viral genetics, and diagnostics in conjunction with novel immunotherapeutic approaches indicate that the time is right to design and perform definitive trials to develop preventive options and curative therapy for JCV-associated diseases.
LB  - PUB:(DE-HGF)16
C6  - 37487750
UR  - <Go to ISI:>//WOS:001158672700001
DO  - DOI:10.1212/WNL.0000000000207622
UR  - https://juser.fz-juelich.de/record/1018540
ER  -