Elimination of intravascular thrombi prevents early mortality and reduces gliosis in hyper-inflammatory experimental cerebral malaria.

BACKGROUND: Cerebral malaria (CM) is the most lethal outcome of Plasmodium infection. There are clear correlations between expression of inflammatory cytokines, severe coagulopathies, and mortality in human CM. However, the mechanisms intertwining the coagulation and inflammation pathways, and their roles in CM, are only beginning to be understood. In mice with T cells deficient in the regulatory cytokine IL-10 (IL-10 KO), infection with Plasmodium chabaudi leads to a hyper-inflammatory response and lethal outcome that can be prevented by anti-TNF treatment. However, inflammatory T cells are adherent within the vasculature and not present in the brain parenchyma, suggesting a novel form of cerebral inflammation. We have previously documented behavioral dysfunction and microglial activation in infected IL-10 KO animals suggestive of neurological involvement driven by inflammation. In order to understand the relationship of intravascular inflammation to parenchymal dysfunction, we studied the congestion of vessels with leukocytes and fibrin(ogen) and the relationship of glial cell activation to congested vessels in the brains of P. chabaudi-infected IL-10 KO mice. METHODS: Using immunofluorescence microscopy, we describe severe thrombotic congestion in these animals. We stained for immune cell surface markers (CD45, CD11b, CD4), fibrin(ogen), microglia (Iba-1), and astrocytes (GFAP) in the brain at the peak of behavioral symptoms. Finally, we investigated the roles of inflammatory cytokine tumor necrosis factor (TNF) and coagulation on the pathology observed using neutralizing antibodies and low-molecular weight heparin to inhibit both inflammation and coagulation, respectively. RESULTS: Many blood vessels in the brain were congested with thrombi containing adherent leukocytes, including CD4 T cells and monocytes. Despite containment of the pathogen and leukocytes within the vasculature, activated microglia and astrocytes were prevalent in the parenchyma, particularly clustered near vessels with thrombi. Neutralization of TNF, or the coagulation cascade, significantly reduced both thrombus formation and gliosis in P. chabaudi-infected IL-10 KO mice. CONCLUSIONS: These findings support the contribution of cytokines, coagulation, and leukocytes within the brain vasculature to neuropathology in malaria infection. Strikingly, localization of inflammatory leukocytes within intravascular clots suggests a mechanism for interaction between the two cascades by which cytokines drive local inflammation without considerable cellular infiltration into the brain parenchyma.

[Toxocara canis cerebral vasculitis revealed by iterative strokes]. / Vascularite cérébrale àToxocara canis révélée par des AVC itératifs.

INTRODUCTION: Cerebral vasculitis is a rare and severe condition, posing problems for diagnosis and treatment. Toxocara canis cerebral vasculitis is exceptionally rare, with only 4 cases having been reported. We report an additional case revealed by iterative strokes. OBSERVATION: A 49-years-old Laotian man presented with right ACA infarction associated with contrast enhancement of cerebrospinal fluid, and multiple segmental stenoses in small and medium caliber encephalic arteries, in a context of hypereosinophilia and chronic headaches. Laboratory tests showed lymphocytic meningitis and T. canis antibody IgE in the blood and CSF. The diagnosis of T. canis cerebral vasculitis was retained. During follow-up, the patient presented again with left pontine hemorrhagic stroke. Conventional cerebral angiography confirmed progression of vasculitis despite treatment. CONCLUSION: This case-report illustrates the diagnostic and therapeutic difficulties associated with vasculitis.

Acute neuroschistosomiasis: two cases associated with cerebral vasculitis.

Encephalitis and focal neurologic deficits can occur during the acute phase of schistosomiasis. We report two cases in which cerebral imaging showed cerebral vasculitis located in arterial junctional territories. These neurologic complications may be caused by eosinophil-mediated toxicity. Immediate treatment should consist of corticosteroids rather than specific antischistosomal drugs, which may aggravate the disorders.