Spinal Arachnoiditis as a Complication of Cryptococcal Meningoencephalitis in Non-HIV Previously Healthy Adults

Abstract

These data suggest that a post-infectious spinal arachnoiditis is an important complication of CM in previously healthy individuals, requiring heightened clinician awareness. Despite microbiological control, this syndrome causes significant pathology likely due to increased inflammation and may be amenable to suppressive therapeutics.

CD4 + T Cells Orchestrate Lethal Immune Pathology despite Fungal Clearance during Cryptococcus neoformans Meningoencephalitis

“…In HIVϩ patients, IRIS frequently arises following restoration of T cell-mediated immunity, and in non-HIV individuals, PIIRS is correlated with elevated CSF CD4 ϩ T cell counts. Both are associated with elevated IFN-␥ and often occur despite successful antifungal therapy and clearance supporting the idea that, as in our murine model, immune pathology is Th1 cell driven and is not solely determined by fungal burden (32,33,(36)(37)(38)(39)(40). How the overexuberant Th1 responses develop in these patients is unknown, but they are possibly linked to myeloid cell dysfunction leading to a persistent overly trigger-sensitive (low-threshold) and hyperactivated state (35,39,71).…”

“…Finally, our findings that CD4 depletion conferred a survival benefit during severe CNS cryptococcosis in mice correlate with cases of severe paradoxical or refractory cryptococcal CNS disease in humans, where the use of steroids has been shown to aid or even be essential for the resolution of clinical symptoms (6,11,27,(32)(33)(34)41). Together, these studies clearly demonstrate that therapies to control or fine-tune the antifungal immune response within CNS can be invaluable to preventing detrimental brain injury.…”

“…Clinical evidence increasingly suggests that the host inflammatory response, rather than pathogen burden, may lead to the development of pathology, neuronal injury, and deteriorating status, especially in IRIS and PIIRS patients (28,30,32,33,(36)(37)(38)(39)(40). Thus, our next goal was to evaluate CNS pathology during the progression of C. neoformans infection and to determine a possible link to the accumulation of a cellular inflammatory response within the CNS.…”

“…T cell inflammatory response in the CNS during cryptococcal meningoencephalitis is highly Th1 polarized, and nearly all CD4 ؉ and CD8 ؉ T cells produce IFN-␥. The subsets of patients with paradoxical inflammatory responses to cryptococcal infection (IRIS and PIIRS) display dominant Th1 T cell polarization with elevated levels of IFN-␥ in the serum and CSF (32,33,(36)(37)(38)(39)(40). Thus, we sought to determine whether murine brain-infiltrating T cells would mimic this phenotype by analyzing T cell cytokine production and expression of polarizing Th-associated transcription factors in the C. neoformans-infected CNS.…”

Arachnoid diverticulum diagnosis following treatment of cryptococcal meningitis in a dog

“…A recent case series describes six previously healthy people of a cohort of 26 diagnosed with cryptococcal meningoencephalitis that developed spinal arachnoiditis . Patients in this study similarly underwent 3–5 lumbar punctures, and it was theorized that inflammation, both during infection and postinfection, created the environment to allow adhesions to form in the subarachnoid space.…”