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. 2023 Jun 1;80(6):624-633.
doi: 10.1001/jamaneurol.2023.0841.

Characteristics of Progressive Multifocal Leukoencephalopathy Associated With Sarcoidosis Without Therapeutic Immune Suppression

Caleb R S McEntire  1 , Anita Fletcher  2 , Michel Toledano  3 , Samantha Epstein  4 , Emily White  5 , C Sabrina Tan  6   7 , Yang Mao-Draayer  8 , Samantha A Banks  3 , Allen J Aksamit  3 , Jeffrey M Gelfand  9 , Kiran T Thakur  10 , Pria Anand  5 , Irene Cortese  11 , Shamik Bhattacharyya  12
Affiliations

Characteristics of Progressive Multifocal Leukoencephalopathy Associated With Sarcoidosis Without Therapeutic Immune Suppression

Caleb R S McEntire et al. JAMA Neurol. .

Abstract

Importance: Progressive multifocal leukoencephalopathy can occur in the context of systemic sarcoidosis (S-PML) in the absence of therapeutic immune suppression and can initially be mistaken for neurosarcoidosis or other complications of sarcoidosis. Earlier recognition of S-PML could lead to more effective treatment of the disease.

Objective: To describe characteristics of patients with S-PML.

Design, setting, and participants: For this case series, records from 8 academic medical centers in the United States were reviewed from 2004 to 2022. A systematic review of literature from 1955 to 2022 yielded data for additional patients. Included were patients with S-PML who were not receiving therapeutic immune suppression. The median follow-up time for patients who survived the acute range of illness was 19 months (range, 2-99). Data were analyzed in February 2023.

Exposures: Sarcoidosis without active therapeutic immune suppression.

Main outcomes and measures: Clinical, laboratory, and radiographic features of patients with S-PML.

Results: Twenty-one patients with S-PML not receiving therapeutic immune suppression were included in this study, and data for 37 patients were collected from literature review. The median age of the 21 study patients was 56 years (range, 33-72), 4 patients (19%) were female, and 17 (81%) were male. The median age of the literature review patients was 49 years (range, 21-74); 12 of 34 patients (33%) with reported sex were female, and 22 (67%) were male. Nine of 21 study patients (43%) and 18 of 31 literature review patients (58%) had simultaneous presentation of systemic sarcoidosis and PML. Six of 14 study patients (43%) and 11 of 19 literature review patients (58%) had a CD4+ T-cell count greater than 200/μL. In 2 study patients, a systemic flare of sarcoidosis closely preceded S-PML development. Ten of 17 study patients (59%) and 21 of 35 literature review patients (60%) died during the acute phase of illness. No meaningful predictive differences were found between patients who survived S-PML and those who did not.

Conclusions and relevance: In this case series, patients with sarcoidosis developed PML in the absence of therapeutic immune suppression, and peripheral blood proxies of immune function were often only mildly abnormal. Systemic sarcoidosis flares may rarely herald the onset of S-PML. Clinicians should consider PML in any patient with sarcoidosis and new white matter lesions on brain magnetic resonance imaging.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Tan reported serving on the scientific advisory board for CellEvolve. Dr Mao-Draayer reported serving as a consultant and/or receiving grant support from Sanofi-Genzyme, Biogen, Chugai, EMD Serono, Genentech, Novartis, Celgene/Bristol Myers Squibb, Janssen, Questor, Horizon, TG Therapeutic, Bayer, Teva, Acorda, AbbVie, Patient-Centered Outcomes Research Institute, and the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID). Dr Gelfand reported grants from Genentech/Roche and Vigil Neurosciences for research support for clinical trials, serving on trial steering committees, and receiving consulting fees from Biogen and Alexion outside the submitted work. Dr Thakur reported grants from the NIH and Centers for Disease Control and Prevention outside the submitted work and being a guest discussant at the 2021 conference Considerations for Progressive Multifocal Leukoencephalopathy Clinical Trial Designs through the Federal Drug Administration. Dr Cortese reported being a shareholder in Nouscom AG, Keires AG, and PDC*line Pharma and sitting on the scientific advisory board for CellEvolve outside the submitted work. Shamik Bhattacharyya reported receiving research support from Alexion Pharmaceuticals, NIH, GlaxoSmithKline, and UCB; consulting for Alexion Pharmaceuticals; receiving publishing honorarium from UpToDate and American Academy of Neurology; and receiving personal fees from Teladoc Health outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow Diagram of Study Inclusion From the Literature Review
Figure 2.
Figure 2.. Enhancing Lesions on Brain Magnetic Resonance Imaging (MRI) of a Male Patient in the Sixth Decade of Life With Progressive Multifocal Leukoencephalopathy in the Context of Sarcoidosis (S-PML)
Brain MRI with corresponding T1 precontrast and postcontrast axial images and T2 fluid-attenuated inversion recovery (FLAIR) coronal and axial images of a male patient in the sixth decade of life who developed PML 7 years after pulmonary sarcoidosis. Punctate enhancement on a milky-way background is seen in panels B and D.
Figure 3.
Figure 3.. Isolated Infratentorial Lesions on Brain Magnetic Resonance Imaging (MRI) of a Male Patient in the Seventh Decade of Life With Progressive Multifocal Leukoencephalopathy in the Context of Sarcoidosis (S-PML)
Brain MRI with corresponding T1 precontrast and T2 fluid-attenuated inversion recovery (FLAIR) axial images of a male patient in the seventh decade of life who developed PML 4 years after multisystemic (lung, skin, liver, heart) sarcoidosis and 6 months after starting prednisone for worsening dyspnea. T2-FLAIR hyperintensities with corresponding T1 hypointensities are seen in the cerebellum, medulla, midbrain, and pons. Nonspecific supratentorial white matter abnormalities were present, but no focal lesions were identified. No enhancement was noted (not shown).
See this image and copyright information in PMC

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