Tuberculous meningitis (TBM) causes significant morbidity and mortality. The primary objective was to re-examine the concept of "TB zone" and "ischaemic zone" in cerebral infarction in patients with tuberculous meningitis. The secondary objective was to evaluate cerebral infarction, vasculitis and vasospasm in tuberculous meningitis infections. Between 2009 and 2014, TBM patients were recruited. Neuroimaging was performed and findings of cerebral infarction, vasculitis and vasospasm were recorded. Infarcts were classified based on arterial supply and Hsieh's classification. Fifty-one TBM patients were recruited of whom 34 patients (67%) had cerebral infarction. Based on Hsieh's classification, 20 patients (59%) had infarcts in both "TB zone" and "ischaemic zones". 12 patients (35%) had infarcts in "ischaemic zone" and two (6%) patients had infarcts in "TB zone". In terms of vascular supply, almost all patients (35/36) had infarcts involving perforators and cortical branches. 25 patients (73%) and 14 patients (41%) had infarcts supplied by lateral lenticulostriate and medial lenticulostriate arteries respectively. 15 patients (37%) had vasculitis. Vasospasm was present in six patients (15%). 29 patients (85%) with cerebral infarction also had leptomeningeal enhancement (p = 0.002). In summary, infarcts involved mainly perforators and cortical branches, rather than "TB zone" versus "ischaemic zone".
A 59-year-old lady with underlying hypothyroidism presented with acute contact dermatitis progressed to cellulitis with superimposed bacterial infection and acute kidney injury. She responded to initial management with antibiotics, but a week later, she had cutaneous and systemic vasculitis. Her skin biopsy consistent with immune-mediated leuko-cytoclastic vasculitis and her blood test was positive for cytoplasmic-anti-neutrophil cytoplasmic antibody (c-ANCA). A diagnosis of ANCA-associated vasculitis was made and she was treated with immunosuppressant with plasmapheresis and hemodialysis support for her kidney failure. Despite aggressive measures, the patient succumbed to her illness. This case report demonstrates that soft tissue infection could trigger the development of ANCA-associated vasculitis whilst a background of hypothyroidism serves as a predisposing factor as both condition were reported separately in a couple of case studies before.
Non-alcoholic fatty liver disease (NAFLD) incorporates steatosis, non-alcoholic steato-hepatitis (NASH) and liver cirrhosis, associating with diabetes and cardiovascular disease (CVD). TNF-related apoptosis-inducing ligand (TRAIL) is protective of CVD. We aimed to determine whether TRAIL protects against insulin resistance, NAFLD and vascular injury. Twelve-week high fat diet (HFD)-fed Trail -/- mice had increased plasma cholesterol, insulin and glucose compared to wildtype. Insulin tolerance was impaired with TRAIL-deletion, with reduced p-Akt, GLUT4 expression and glucose uptake in skeletal muscle. Hepatic triglyceride content, inflammation and fibrosis were increased with TRAIL-deletion, with elevated expression of genes regulating lipogenesis and gluconeogenesis. Moreover, Trail -/- mice exhibited reduced aortic vasorelaxation, impaired insulin signaling, and >20-fold increased mRNA expression for IL-1β, IL-6, and TNF-α. In vitro, palmitate treatment of hepatocytes increased lipid accumulation, inflammation and fibrosis, with TRAIL mRNA significantly reduced. TRAIL administration inhibited palmitate-induced hepatocyte lipid uptake. Finally, patients with NASH had significantly reduced plasma TRAIL compared to control, simple steatosis or obese individuals. These findings suggest that TRAIL protects against insulin resistance, NAFLD and vascular inflammation. Increasing TRAIL levels may be an attractive therapeutic strategy, to reduce features of diabetes, as well as liver and vascular injury, so commonly observed in individuals with NAFLD.