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Outcomes in Previously Healthy Cryptococcal Meningoencephalitis Patients Treated With Pulse Taper Corticosteroids for
Seher Anjum1, Owen Dean1, Peter Kosa1
1Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
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.
Insights
Pulse corticosteroid taper therapy (PCT) improved outcomes for cryptococcal meningoencephalitis (CM) with post-infectious inflammatory response syndrome (PIIRS) in previously healthy individuals. This treatment enhanced cognitive function, vision, and hearing, with positive MRI findings and reduced inflammation.
Area of Science:
- Neurology
- Infectious Diseases
- Immunology
Background:
- Cryptococcal meningoencephalitis (CM) is a significant cause of mortality, particularly in immunocompromised individuals.
- In previously healthy patients, CM can present with a post-infectious inflammatory response syndrome (PIIRS), leading to poor outcomes despite antifungal treatment.
- Limited data exist on effective therapeutic strategies for CM with PIIRS.
Purpose of the Study:
- To evaluate the efficacy of adjunctive pulse corticosteroid taper therapy (PCT) in previously healthy patients with CM and PIIRS.
- To assess the impact of PCT on clinical, cognitive, radiological, and immunological parameters.
Main Methods:
- A cohort of 15 previously healthy patients with CM and PIIRS received PCT (methylprednisolone followed by prednisone) alongside fluconazole.
- Patients underwent assessments including Montreal Cognitive Assessment (MOCA), Karnofsky performance scores, MRI, and cerebrospinal fluid (CSF) analysis before and after treatment.
- Comparisons were made for cognitive function, performance status, neurological imaging, and CSF inflammatory markers.
Main Results:
- Adjunctive PCT significantly improved MOCA and Karnofsky scores within one month of treatment.
- Patients showed marked improvements in CSF parameters, including glucose, WBC count, protein, and inflammatory markers, after corticosteroid initiation.
- Significant improvements were observed in visual deficits, hearing, and brain MRI findings, with CSF cultures remaining negative.
Conclusions:
- Pulse corticosteroid taper therapy (PCT) demonstrated significant clinical benefits in a small cohort of previously healthy patients with CM and PIIRS.
- PCT was associated with improvements in neurological complications and inflammatory markers with minimal acute toxicity.
- These findings suggest PCT as a potentially valuable adjunctive treatment for CM-related PIIRS.
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