47 - Long Term Outcomes of Pulse-taper Corticosteroid Therapy (PCT) for Refractory Non-hiv Cryptococcal Meningoencephalitis

Background: Cryptococcal meningoencephalitis (CM) is a major cause of mortality in HIV/AIDS, transplant recipients and previously healthy individuals. In the latter, a post-infectious inflammatory response syndrome (PIIRS) is associated with poor clinical response despite prior amphotericin  therapy and CSF culture conversion. Data on effective treatment is limited.

Methods: Between March 2015 and March 2020, 15 patients with CM/PIIRS were treated with adjunctive pulse – taper corticosteroid therapy (PCT) consisting of intravenous methylprednisolone 1 gm daily for 1 week followed by oral prednisone 1 mg/kg/d, tapered based on clinical and radiological response plus oral fluconazole. Montreal cognitive assessments (MOCA), Karnofsky Performance scores, MRI brain scans, eye and audiologic exams were conducted at baseline and after pulse completion. CSF parameters were assessed prior to and after the pulse.

Results: 80% of patients were male, median age 51 years. Median time from antifungal treatment to steroid initiation was 6 weeks. The most common symptoms at PIIRS diagnosis were progressive deterioration in mental status and vision changes. There was a significant improvement in MOCA(n=14) and Karnofsky(n=15) scores at 3 weeks (p< 0.0003), which was accompanied by improvements in CSF: serum, glucose ratios, CSF WBC, protein and activated CD4 T cells (n=14) post-pulse (p< 0.003). Additionally, soluble CSF IL-6 and  sCD25 levels improved ( p = 0.03). Neurofilament light chain levels (NFL), a biomarker of axonal damage, showed significant reductions over a 30-month period (Generalized Estimating Equation coefficient = 0.128) and a negative correlation with post pulse MOCA scores (r = - 0.8; p = 0.01).
 
Papilledema (n=8) and visual field deficits (n=11) improved significantly (p< 0.0005) after 2 months of pulse completion. Brain MRI showed improvement of radiological findings in 11 patients (p=0.001). Five out of 7 patients who underwent audiological testing demonstrated hearing improvement after 3 weeks post-pulse. CSF cultures remained negative.MOCA and Karnofsky score comparison at baseline and post pulse corticosteroid


Conclusion: PCT in this small cohort of PIIRS patients was associated with persistent improvements in CM-related complications with minimal toxicity and no recurrence of infection.
 
 

Presenting Author(s)

• 

  Seher Anjum, MD

  Staff clinician
  NIAID
  Bethesda, MD

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

  Slides Slides and Audio

Co-Author(s)

• PW

  Peter Williamson, MD, PhD

  MD, PhD
  National Institutes of Health, Bethesda
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• TM

  Teresa Magone, MD

  MD
  NEI
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• FE

  Fitzgibbon Edmond, MD

  MD
  NEI
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• CK

  Chantal Krieger, MD

  MD
  NEI
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• EM

  Elizabeth Murphy, PhD

  PhD
  NEI
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• CZ

  Chris Zalewski, PhD

  PhD
  NIDCD
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• KK

  Kelly King, PhD

  PhD
  NIDCD
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• JC

  Jennifer Chisholm, AuD

  Audiology Extern
  NIDCD
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• CB

  Carmen Brewer, PhD

  PhD
  NIDCD
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• AN

  Avindra Nath, MD

  Clinical Director
  National Institute of Neurological Disorders and Stroke
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• JB

  Jean Billioux, MD

  MD
  NINDS
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• PK

  Peter Kosa, PhD

  PhD
  National Institutes of Health
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• BB

  Bibiana Bielekova, MD

  MD
  National Institutes of Health
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• JB

  John Bennett, MD

  MD
  NIAID
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• KM

  Kieren Marr, MD

  MD
  John Hopkins
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• DH

  Dima Hammoud, MD

  Tenure Track Investigator
  NIH Clinical Center
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• OD

  Owen Dean, medical student

  medical student
  University of Rochester
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• JK

  Jeff Kim, MD

  MD
  NIDCD
  Bethesda, Maryland

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.