Citations

Background and Purpose— Patients with aneurysmal subarachnoid hemorrhage are typically kept in the intensive care unit to be monitored for signs of delayed cerebral ischemia (DCI). Identifying patients at lower risk for DCI could have a positive financial impact by allowing earlier transfer from the intensive care unit. Methods— We analyzed 307 consecutive patients admitted to the intensive care unit. Demographic, clinical, and neuroimaging data were recorded. The relationship with absent DCI was analyzed using univariate and multivariate logistic regression models. Results— DCI did not develop in 169 patients (57.9%). Among factors at admission, age 68 years or older ( P =0.0003; OR, 3.16; 95% CI, 1.66–6.39), World Federation of Neurological Surgeons (WFNS) I to III at presentation ( P =0.0003; OR, 2.73; 95% CI, 1.57–4.79), WFNS I to III at worst ( P =0.0003; OR, 2.39; 95% CI, 1.48–3.87), WFNS I to III after resuscitation ( P =0.0006; OR, 2.85; 95% CI, 1.56–5.32), modified Fisher grade 1 to 2 ( P =0.0021; OR, 2.43; 95% CI, 1.37–4.47), absence of intracranial hematoma ( P =0.0042; OR, 2.26; 95% CI, 1.29–4.01), and aneurysm in the posterior circulation ( P =0.025; OR, 1.74; 95% CI, 1.07–2.87) were associated with absence of DCI. On multivariate analysis, a model including age 68 years or older, WFNS I to III at presentation and a modified Fisher grade 1 to 2 were independently predictive of the absence of DCI, with a specificity of 100% and a positive predictive value of 100%. Conclusions— We propose a new model that can reliably identify patients with aneurysmal subarachnoid hemorrhage who are at very low risk for DCI. These patients could be candidates for early transfer to the general ward.

ABSTRACT Antibodies to viral surface glycoproteins play a crucial role in immunity to measles by blocking both virus attachment and subsequent fusion with the host cell membrane. Here, we demonstrate that certain immunoglobulin G (IgG) antibodies can also enhance the entry of measles virus (MV) into monocytes and macrophages. Antibody-dependent enhancement of infectivity was observed in mouse and human macrophages using virions opsonized by a murine monoclonal antibody against the MV hemagglutinin (H) glycoprotein, polyclonal mouse anti-MV IgG, or diluted measles-immune human sera. Neither H-specific Fab fragments nor H-specific IgM could enhance MV entry in monocytes or macrophages, indicating involvement of a Fc γ receptor (FcγR)-mediated mechanism. Preincubation with an anti-fusion protein (anti-F) monoclonal antibody or a fusion-inhibitory peptide blocked infection, indicating that a functional F protein was required for viral internalization. Classical complement pathway activation did not promote infection through complement receptors and inhibited anti-H IgG-mediated enhancement. In vivo, antibody-enhanced infection allowed MV to overcome a highly protective systemic immune response in preimmunized IfnarKo-Ge46 transgenic mice. These data demonstrate a previously unidentified mechanism that may contribute to morbillivirus pathogenesis where H-specific IgG antibodies promote the spread of MV infection among FcγR-expressing host cells. The findings point to a new model for the pathogenesis of atypical MV infection observed after immunization with formalin-inactivated MV vaccine and underscore the importance of the anti-F response after vaccination.