ABSTRACT
Bacterial meningitis is a life-threatening disease that evokes an intense neutrophil-dominated host response to microbes invading the subarachnoid space. Recent evidence indicates the existence of combinatorial V(D)J immune receptors in neutrophils that are based on the T cell receptor (TCR). Here, we investigated expression of the novel neutrophil TCRαß-based V(D)J receptors in cerebrospinal fluid (CSF) from human patients with acute-phase bacterial meningitis using immunocytochemical, genetic immunoprofiling, cell biological, and mass spectrometric techniques. We find that the human neutrophil combinatorial V(D)J receptors are rapidly induced in CSF neutrophils during the first hours of bacterial meningitis. Immune receptor repertoire diversity is consistently increased in CSF neutrophils relative to circulating neutrophils and phagocytosis of baits directed to the variable immunoreceptor is enhanced in CSF neutrophils during acute-phase meningitis. Our results reveal that a flexible immune response involving neutrophil V(D)J receptors which enhance phagocytosis is immediately initiated at the site of acute bacterial infection.
ABSTRACT
BACKGROUND AND PURPOSE: Patients with cardioembolic ischemic stroke from nonvalvular atrial fibrillation (NVAF) are candidates for long-term anticoagulation. This study examines the prevalence of cerebral microbleeds (MBs) in stroke patients with NVAF. METHODS: A total of 132 consecutive ischemic stroke patients with NVAF admitted to our Stroke Unit were recruited if complete magnetic resonance (MR) imaging studies including T2* imaging had been performed within less than 72 hours. National Institutes of Health Stroke Scale scores were documented and cerebrovascular risk factors were monitored. RESULTS: Among 132 patients (mean age 74.1±9.8 years), only 9 (6.8%) had MBs (mean number 6.2) as detected on T2* MR images. No statistically significant differences between patients without versus with MBs were observed regarding arterial hypertension, diabetes, hyperlipidemia, and coronary heart disease. However, small vessel disease (SVD) was significantly more frequent in patients with MBs than without MBs (44.4% vs. 12.2%; P<.05) and significantly more patients with MBs experienced repeated strokes (44.4% vs. 14.6%; P<.05). CONCLUSIONS: In contrast to studies reflecting a high incidence of MBs in stroke patients of various subtypes, MBs occurred less frequently in patients with cardioembolic acute ischemic stroke associated with NVAF. In patients with severe SVD or repeated cerebrovascular events, special caution should be taken regarding oral anticoagulation.
Subject(s)
Atrial Fibrillation/complications , Cerebral Hemorrhage/etiology , Magnetic Resonance Imaging , Stroke/etiology , Adult , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Atrial Fibrillation/drug therapy , Cerebral Hemorrhage/drug therapy , Comorbidity , Female , Humans , Male , Middle Aged , Risk Factors , Stroke/drug therapySubject(s)
Herpes Simplex/etiology , Herpes Simplex/genetics , Herpesvirus 2, Human/pathogenicity , Meningitis/etiology , Meningitis/genetics , Toll-Like Receptor 3/deficiency , Enzyme-Linked Immunosorbent Assay/methods , Herpes Simplex/complications , Humans , Male , Meningitis/complications , Middle Aged , Toll-Like Receptor 3/metabolismABSTRACT
BACKGROUND: The management and risk of early stroke are unclear in patients with fluctuating neurological symptoms. We aimed to evaluate the clinical course of these patients presenting within 24 h after onset of acute cerebral ischemia symptoms. METHODS: All patients with transient ischemic signs/symptoms consecutively admitted to our Emergency Stroke Unit were recruited. Patients were neurologically examined and underwent prompt CCT plus MRI imaging for visualization of early signs of ischemia. RESULTS: Among 122 patients, 84 (69%) had single symptoms, 33 (27%) showed rapidly relapsing and remitting symptoms - in 5 cases (4%) symptom duration could not reliably be assessed. 11/122 (9%) suffered a stroke during hospitalization. ABCD(2) scores did not predict early strokes: 2/11 (18.2%) were in the 'lower risk', 7/11 (63.6%) in the 'moderate risk' and only 2/11 (18.2%) in the 'high risk' group (p = 0.103). 3/11 patients (27.3%) revealed lesions in neuroimaging, but surprisingly 8/11 (72.7%, p = 0.132) did not. However, patients with fluctuations in neurological status were significantly more likely to suffer a stroke: 9/122 versus 2/122 with stable symptoms (p < 0.05). Patients with small vessel disease were common in all (53/ 122; 43.4%) and within those who suffered an early stroke (6/11; 54.5%). CONCLUSIONS: Patients with unstable transient ischemic attacks immediately after onset of clinical symptoms are at high risk for subsequent stroke - they may benefit from Stroke Unit management and potential early thrombolysis once they develop strokes.
