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

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 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/d, tapered based on clinical and radiological response plus oral fluconazole. Montreal Cognitive Assessments (MOCA), Karnofsky Performance scores, MRI brain scanning, ophthalmic and audiologic exams, 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<0.0003), which was accompanied by improvements in CSF glucose, WBC, protein, cellular and soluble inflammatory markers 1 week after receiving corticosteroids (CS) (p<0.003). All patients with papilledema and visual field deficits also exhibited improvement (p<0.0005). Five out of 7 patients who underwent audiological testing demonstrated hearing improvement. Brain MRI showed significant improvement of radiological findings (p=0.001). 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.

Maternal outcomes and risk factors for COVID-19 severity among pregnant women

“…The clinical relevance of this finding remains unclear, as, at the time of the study, we were lacking comprehensive data regarding COVID-related symptoms or COVID-suspected symptoms among newborns, repeated testing and long-term follow-up. Perinatal transmission of SARS-CoV-2 has been reported by others, both in case of vaginal and cesarean sections, and was associated in some cases with neonatal symptoms 1 , 4 , 22 . In all reported cases, the possibility of postnatal infection through contacts with parents or medical personal remains difficult to exclude 1 , 4 .…”

Cryptococcal Meningitis and Post-Infectious Inflammatory Response Syndrome in a Patient With X-Linked Hyper IgM Syndrome: A Case Report and Review of the Literature

“…This altered balance results in an excessive host immune response to infection within the space-confines of the skull, causing significant pathology (32), even in the presence of reduced CD40L signaling, as suggested by the present case. During PIIRS an appropriate pro-inflammatory cytokine response including interferon (IFN)-g and interleukin (IL)-6 stimulates T helper cells to cause immune cells immune mediated host damage but with an alternately activated macrophage subtype (M2) that is less effective at clearing nonviable fungal debris (33,34). This paradoxical immune response has been studied by Panackal et al analyzing the soluble and cellular responses to Cryptococcus in both blood and CSF in a consecutive cohort of non-HIV, nontransplant individuals with no comorbidities or iatrogenic immunosuppression who developed severe central nervous system disease (s-CNS) (24).…”

“…However, after fungicidal therapy by agents such as amphotericin B, rupture of the fungus releases internal proteins and exposes cell wall antigens that provide additional antigenic targets recognizable by the immune-deficient host without a need for immune reconstitution as in HIV-related IRIS (24). Indeed, in a previous report (33), patients with idiopathic CD4 lymphopenia and autoantibodies to granulocyte-monocytic colony stimulating factor (anti-GMCSF), well recognized risk factors for cryptococcal disease (3) developed PIIRS after therapy as in the present case that was also responsive to corticosteroids. Thus, this case extends the spectrum of patients described with PIIRS and the generalizability of this adjuctive therapy in PIIRS.…”

“…While the use of corticosteroids (CST) has proven to lack efficacy in patients with HIV-associated CM (36), despite the lack of consensus regarding the management of PIIRS associated to CM, there are data from the literature (30,33) with evidence of beneficial effect from adjunctive CS therapy (31) to the usual antimicrobial agents.…”

Early and long term antibody kinetics of asymptomatic and mild disease COVID-19 patients

“…The magnitude of the antibody response may be associated with disease severity, and it has been reported that patients with mild infections may not develop detectable amounts of neutralizing antibodies 3 , 4 , 9 . However, the exact nature of seroconversion with respect to patient risk factors and disease severity is still controversial 4 , 6 , 7 , 10 , 11 .…”