Seher Anjum1, Owen Dean1, Peter Kosa1, M Teresa Magone2, Kelly A King3, Edmond Fitzgibbon2, H Jeff Kim3, Chris Zalewski3, Elizabeth Murphy2, Bridgette Jeanne Billioux4, Jennifer Chisholm3, Carmen C Brewer3, Chantal Krieger2, Waleed Elsegeiny1, Terri L Scott1, Jing Wang5, Sally Hunsberger6, John E Bennett1, Avindra Nath4, Kieren A Marr7, Bibiana Bielekova1, David Wendler8, Dima A Hammoud9, Peter Williamson1. 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
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.
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.
Authors: Kieren A Marr; Yifei Sun; Andrej Spec; Na Lu; Anil Panackal; John Bennett; Peter Pappas; Darin Ostrander; Kausik Datta; Sean X Zhang; Peter R Williamson Journal: Clin Infect Dis Date: 2020-01-02 Impact factor: 9.079
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Authors: Katherine Traino; Joseph Snow; Lillian Ham; Angela Summers; Laura Segalà; Talia Shirazi; Nadia Biassou; Anil Panackal; Seher Anjum; Kieren A Marr; William C Kreisl; John E Bennett; Peter R Williamson Journal: Sci Rep Date: 2019-12-05 Impact factor: 4.379