Progressive Multifocal Leukoencephalopathy Associated With Sarcoidosis: A Multi-Center Case Series

Abstract

Objective We aim to describe the clinical, laboratory, and radiographic features that characterize patients with progressive multifocal leukoencephalopathy (PML) in the context of sarcoidosis (S-PML). Background Sarcoidosis has been associated with CD4+, CD8+, and CD19+ lymphopenia, T-cell anergy, and increased infection risk. S-PML has been reported in approximately 60 cases. PML is often mistaken for neurosarcoidosis, leading to harmful administration of high-dose steroids. Preliminary evidence suggests that experimental therapies such as interleukins 2 and 7, checkpoint inhibitors, polyomavirus-specific T-cell therapy, and infliximab may offer promise for treatment. To ensure optimal outcome, it is crucial to identify S-PML accurately and with minimal delay. Design/Methods Data and imaging for patients were collected retrospectively from the electronic medical record from Mass General-Brigham network hospitals, National Institutes of Health, Mayo Clinic, Columbia University Irving Medical Center, University of California San Francisco, University of Michigan, and Beth Israel Deaconess Medical Center. Results Twenty-five patients with definite S-PML were identified. Median age at diagnosis of sarcoidosis was 54 years, and median time between sarcoidosis and PML diagnosis was 12 months. Sarcoidosis was isolated to lung in 14/25 patients; 10/25 had multisystem involvement; one patient had isolated dermatologic sarcoidosis. Of all patients, 16/25 patients had never received immunosuppressive medications prior to neurological symptom onset. Median serum lymphocyte count at time of PML diagnosis was 430 cells/uL (range: 50-1490). On MRI, 8/25 patients had infratentorial lesions only, while 8/25 had both infratentorial and supratentorial lesions, and 6/25 showed contrast enhancement. Seven/twenty-five patients progressed to death. Conclusions This study characterizes the clinical, laboratory, and imaging features of S-PML patients from seven major US medical centers. These data will be used to identify risk factors for development of PML in the context of sarcoidosis and to investigate any biomarkers that might aid in accurate and timely diagnosis.