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Introduction: Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) can be reversible or progress to cerebral infarction. In patients with a deterioration clinically diagnosed as DCI, we investigated whether CT perfusion (CTP) can distinguish between reversible ischemia and ischemia progressing to cerebral infarction., Methods: From a prospectively collected series of aSAH patients, we included those with DCI, CTP on the day of clinical deterioration, and follow-up imaging. In qualitative CTP analyses (visual assessment), we calculated positive and negative predictive value (PPV and NPV) with 95% confidence intervals (95%CI) of a perfusion deficit for infarction on follow-up imaging. In quantitative analyses, we compared perfusion values of the least perfused brain tissue between patients with and without infarction by using receiver-operator characteristic curves and calculated a threshold value with PPV and NPV for the perfusion parameter with the highest area under the curve., Results: In qualitative analyses of 33 included patients, 15 of 17 patients (88%) with and 6 of 16 patients (38%) without infarction on follow-up imaging had a perfusion deficit during clinical deterioration (p = 0.002). Presence of a perfusion deficit had a PPV of 71% (95%CI: 48-89%) and NPV of 83% (95%CI: 52-98%) for infarction on follow-up. Quantitative analyses showed that an absolute minimal cerebral blood flow (CBF) threshold of 17.7 mL/100 g/min had a PPV of 63% (95%CI: 41-81%) and a NPV of 78% (95%CI: 40-97%) for infarction., Conclusions: CTP may differ between patients with DCI who develop infarction and those who do not. For this purpose, qualitative evaluation may perform marginally better than quantitative evaluation.

Background and Purpose: Despite a significant reduction of angiographic vasospasm, the reduction of poor functional outcome in clinical trials on aneurysmal subarachnoid hemorrhage (SAH) remains challenging. While there is general consensus that vasospasm is associated with delayed cerebral ischemia (DCI), cerebral infarction, poor functional outcome, and mortality after SAH, causal relationships are subject to discussion. Therefore, it was the aim of our study to investigate the relationship between various outcome measures and poor functional outcome in clinical trials on pharmaceutical treatment of SAH., Methods: Based on data from two systematic reviews and a post hoc exploratory analysis, the relationship between the following outcome measures was investigated: (1) radiographic vasospasm, (2) DCI, (3) cerebral infarction, (4) poor functional outcome, and (5) death., Results: A reduction of angiographic vasospasm did not correlate with an improvement on dichotomous Glasgow Outcome Scale/modified Rankin Scale (GOS/mRS). In contrast, a reduction of cerebral infarction correlated with better neurological outcomes. The heterogeneous definition of DCI in previous clinical trials did not allow pooling of the data., Conclusion: Future clinical trials may use cerebral infarction and functional outcome as main outcome measures to -investigate the true impact of an intervention, assuming that the intervention targets cerebral infarction and hereby improves outcome.

Background: To evaluate clinical features and prognostic factors of cerebral infarctions in adults with community-acquired bacterial meningitis., Method: An observational cross-sectional study, including 696 patients of whom 174 had cerebral infarction, from a prospective nationwide cohort of community-acquired bacterial meningitis (period, 1998-2002), confirmed by culture of cerebral spinal fluid (CSF) in patients aged over 16 years. Two investigators independently determined the presence of infarction., Result: Cerebral infarction occurred in 174 episodes (25%), with a high inter-rater agreement for determining the presence of cerebral infarction (kappa 0.95). Cerebral infarctions occurred in 128 of 352 patients (36%) with pneumococcal meningitis, in 22 of 257 (9%) with meningococcal meningitis and in 24 of 87 patients (28%) with meningitis caused by other bacteria. Patients with infarctions were older (P < 0.001) and often presented with predisposing conditions, such as otitis and/or sinusitis (P = 0.001) or an immunocompromised state (P = 0.003) compared to those without infarction. Patients with infarctions presented with lower scores on the Glasgow Coma Scale (P < 0.001), lower CSF white cell counts (P = 0.001), and higher serum erythrocyte sedimentation rate (ESR) (P < 0.001). Unfavorable outcome occurred in 108 (62%) patients with infarctions. In a multivariate analysis, infarction was related with unfavorable outcome (odds ratio 3.37; 95% confidence interval 2.19-5.21; P < 0.001). We identified lower CSF white cell counts and high ESR to be independent risk factors for cerebral infarction., Conclusion: Cerebral infarction is a common and severe complication in adults with community-acquired bacterial meningitis. Preventing cerebral infarctions will be important in reducing the high morbidity and mortality rate in adults with community-acquired bacterial meningitis.

Delayed cerebral ischemia occurs in about 30% of patients during the first 2 weeks after subarachnoid hemorrhage, and can result in substantial disability and death. Research studies investigating the incidence of delayed cerebral ischemia and strategies for prevention and treatment are hampered by inconsistent use of terminology and definitions for this complication, and by reliance on indirect surrogate markers of ischemia. A literature review was conducted to search for studies that addressed the issue of inconsistent definitions of delayed cerebral ischemia through December 2010. A total of four studies were identified. Original research studies and consensus panel recommendations for definitions support limiting the use of combined measures that include both clinical and radiographic assessments, as well as indirect measures, and the current usage of the term vasospasm. Cerebral infarction was supported as the most appropriate definition for delayed cerebral ischemia in the context of clinical trials.

Despite an undisputed association between vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH), there is debate if this association implies causality. It has been suggested that cerebral infarction is a better outcome measure than vasospasm in clinical trials and observational studies. To further investigate the relationship between infarction and outcome, we performed a systematic review and meta-analysis of all randomized, double-blind, placebo-controlled trials that studied the efficacy of pharmaceutical preventive strategies in SAH patients, and had both cerebral infarction and clinical outcome as outcome events. Effect sizes were expressed in (pooled) risk ratio (RR) estimates with corresponding 95% confidence intervals (CIs). Sensitivity analyses were performed for studies with a low risk of bias and for those who reported outcome at 3 months after SAH. Twenty-four studies including 8,552 patients were included. Pharmaceutical treatments decreased the incidence of both cerebral infarction (RR: 0.83; 95% CI: 0.74 to 0.93) and of poor functional outcome (RR: 0.92; 95% CI: 0.86 to 0.98). The sensitivity analyses did not change the results essentially. These data suggest that the previously observed association between cerebral infarction and functional outcome implies causality, and that cerebral infarction is a better outcome measure than vasospasm in clinical trials and observational studies.

Background and Purpose: The pathogenesis of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage remains incompletely understood. It is generally assumed that it is caused by angiographic vasospasm. Our aim was to clarify the relationship among angiographic vasospasm, neurological worsening, cerebral infarction, and poor outcome and to investigate whether cerebral infarction also contributes to poor outcome by vasospasm-independent effects., Methods: This exploratory analysis used data from 413 patients included in the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial. We studied the incidence of neurological worsening, cerebral infarction, and poor outcome in patients with and without angiographic vasospasm. Path analysis implemented by structural equation modeling was performed to determine direct and indirect path coefficients., Results: Of the 194 patients with moderate to severe vasospasm, 43% had neurological worsening of any cause, 20% had cerebral infarction, and 46% poor outcome. Path coefficients for direct effects on poor outcome were 0.20 for World Federation of Neurological Surgeons Grade 4 to 5, 0.13 for history of hypertension, 0.19 for angiographic vasospasm, 0.16 for neurological worsening, and 0.11 for new cerebral infarction. Cerebral infarction contributed to poor outcome by vasospasm-dependent and -independent effects., Conclusions: Our data show that the majority of patients with moderate to severe angiographic vasospasm did not have neurological worsening of any cause or cerebral infarction. Besides, cerebral infarction also has a direct effect on outcome independent of angiographic vasospasm. This suggests that other coexisting factors might be involved in the pathogenesis of delayed cerebral ischemia, which should also be an important research target to improve outcome after subarachnoid hemorrhage.

Background: There is a widely held belief that cerebral infarction after bacterial meningitis is always caused by vasculitis; however, evidence is weak. We hypothesized that diffuse cerebral intravascular coagulation is an additional explanation of cerebral infarction in patients with pneumococcal meningitis., Methods: Sixteen brains of adults who died from pneumococcal meningitis were investigated. Clinical data were collected, and brain sections were scored for signs of inflammation and activation of coagulation. Patients with and without cerebral infarction on autopsy were compared., Results: In total, 38% of patients had focal neurological deficits. Patients died at a median of 7 days (range, 0-32 days) after admission. On autopsy, the nine patients (56%) with cerebral infarctions more often had arterial thrombosis (p = 0.04) than patients without infarction. Patients with infarction tended to have more inflammatory infiltrations of brain parenchyma, microvascular proliferation, small vessel vasculitis/endarteritis obliterans, blood clotting/vessel clogging, and venous thrombosis. None of the patients had large vessel vasculitis. Five patients had cerebral infarctions without vasculitis or endarteritis obliterans. Although four patients with cerebral infarctions had small vessel vasculitis or endarteritis obliterans, areas of infarction could not be localized to the blood flow distribution of these vessels. Blood clotting/vessel clogging was seen in all four patients with vasculitis or endarteritis obliterans, but this was also observed in 10 patients without vasculitis or endarteritis obliterans. None of the patients developed disseminated intravascular coagulation., Conclusions: Our results suggest that diffuse cerebral intravascular coagulation is an additional explanation of cerebral infarction complicating pneumococcal meningitis.