Outcomes in Previously Healthy Cryptococcal Meningoencephalitis Patients Treated With Pulse Taper Corticosteroids for Post-infectious Inflammatory Syndrome

Author:

Anjum Seher1,Dean Owen1,Kosa Peter1,Magone M Teresa2,King Kelly A3,Fitzgibbon Edmond2,Kim H Jeff3,Zalewski Chris3,Murphy Elizabeth2,Billioux Bridgette Jeanne4,Chisholm Jennifer3,Brewer Carmen C3,Krieger Chantal2,Elsegeiny Waleed1,Scott Terri L1,Wang Jing5,Hunsberger Sally6,Bennett John E1,Nath Avindra4,Marr Kieren A7,Bielekova Bibiana1,Wendler David8,Hammoud Dima A9,Williamson Peter1

Affiliation:

1. Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA

2. National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA

3. National Institute on Deafness and Other Communication Disorders, National Institute of Health, Bethesda, Maryland, USA

4. Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA

5. Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA

6. Biostatistics Research Branch, NIAID, Bethesda, Maryland, USA

7. Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA

8. Department of Bioethics, Bethesda, Maryland, USA

9. Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA

Abstract

Abstract Background Cryptococcal meningoencephalitis (CM) is a major cause of mortality in immunosuppressed patients and previously healthy individuals. In the latter, a post-infectious inflammatory response syndrome (PIIRS) is associated with poor clinical response despite antifungal therapy and negative cerebrospinal fluid (CSF) cultures. Data on effective treatment are limited. Methods Between March 2015 and March 2020, 15 consecutive previously healthy patients with CM and PIIRS were treated with adjunctive pulse corticosteroid taper therapy (PCT) consisting of intravenous methylprednisolone 1 gm daily for 1 week followed by oral prednisone 1 mg/kg/day, tapered based on clinical and radiological response plus oral fluconazole. Montreal cognitive assessments (MOCA), Karnofsky performance scores, magnetic resonance imaging (MRI) brain scanning, ophthalmic and audiologic exams, and CSF parameters including cellular and soluble immune responses were compared at PIIRS diagnosis and after methylprednisolone completion. Results The median time from antifungal treatment to steroid initiation was 6 weeks. The most common symptoms at PIIRS diagnosis were altered mental status and vision changes. All patients demonstrated significant improvements in MOCA and Karnofsky scores at 1 month (P < .0003), which was accompanied by improvements in CSF glucose, white blood cell (WBC) count, protein, cellular and soluble inflammatory markers 1 week after receiving corticosteroids (CS) (P < .003). All patients with papilledema and visual field deficits also exhibited improvement (P < .0005). Five out of 7 patients who underwent audiological testing demonstrated hearing improvement. Brain MRI showed significant improvement of radiological findings (P = .001). CSF cultures remained negative. Conclusions PCT in this small cohort of PIIRS was associated with improvements in CM-related complications with minimal toxicity in the acute setting.

Funder

Intramural Research Program of the National Institutes of Health

National Cancer Institute

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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