Hemorrhage in the central nervous system (CNS), including intracerebral hemorrhage (ICH), intraventricular hemorrhage (IVH), and aneurysmal subarachnoid hemorrhage (aSAH), remains highly morbid. Trials of medical management for these conditions over recent decades have been largely unsuccessful in improving outcome and reducing mortality. Beyond its role in creating mass effect, the presence of extravasated blood in patients with CNS hemorrhage is generally overlooked. Since trials of surgical intervention to remove CNS hemorrhage have been generally unsuccessful, the potent neurotoxicity of blood is generally viewed as a basic scientific curiosity rather than a clinically meaningful factor. In this review, we evaluate the direct role of blood as a neurotoxin and its subsequent clinical relevance. We first describe the molecular mechanisms of blood neurotoxicity. We then evaluate the clinical literature that directly relates to the evacuation of CNS hemorrhage. We posit that the efficacy of clot removal is a critical factor in outcome following surgical intervention. Future interventions for CNS hemorrhage should be guided by the principle that blood is exquisitely toxic to the brain.

BACKGROUND: Malignant cerebral edema (MCE) and intracranial hemorrhage (ICH) are associated with poor neurological outcomes despite revascularization after mechanical thrombectomy (MT). The factors associated with the development of MCE and ICH after MT are not well understood. OBJECTIVE: To determine periprocedural factors associated with MCE, ICH, and poor functional outcome. METHODS: We retrospectively analyzed anterior cerebral circulation large vessel occlusion cases that underwent MT from 2012 to 2019 at a single Comprehensive Stroke Center. Multivariate logistic regression analyses were performed to determine significant predictors of MCE, ICH, and poor functional outcome (modified Rankin Scale, 3-6) at 90 d. RESULTS: Four hundred patients were included. Significant independent predictors of MCE after MT included initial stress glucose ratio (iSGR) (odds ratio [OR], 14.26; 95% CI, 3.82-53.26; P < .001), National Institutes of Health Stroke Scale (NIHSS) (OR, 1.10; 95% CI, 1.03-1.18; P = .008), internal carotid artery compared with M1 or M2 occlusion, and absence of successful revascularization (OR, 0.16; 95% CI, 0.06-0.44; P < .001). Significant independent predictors of poor functional outcome included MCE (OR, 7.47; 95% CI, 2.20-25.37; P = .001), iSGR (OR, 5.15; 95% CI, 1.82-14.53; P = .002), ICH (OR, 4.77; 95% CI, 1.20-18.69; P = .024), NIHSS (OR, 1.10; 95% CI, 1.05-1.16; P < .001), age (OR, 1.04; 95% CI, 1.03-1.07; P < .001), and thrombolysis in cerebral infarction 2C/3 recanalization (OR, 0.12; 95% CI, 0.05-0.29; P < .001). CONCLUSION: Elevated iSGR significantly increases the risk of MCE and ICH and is an independent predictor of poor functional outcome. Thrombolysis in cerebral infarction 2C/3 revascularization is associated with reduced risk of MCE, ICH, and poor functional outcome. Whether stress hyperglycemia represents a modifiable risk factor is uncertain, and further investigation is warranted.

BACKGROUND: Patients who survive aneurysmal subarachnoid hemorrhage (aSAH) are at risk for delayed neurological deficits (DND) and cerebral infarction. In this exploratory cohort comparison analysis, we compared in-hospital outcomes of aSAH patients administered a low-dose intravenous heparin (LDIVH) infusion (12 U/kg/h) vs those administered standard subcutaneous heparin (SQH) prophylaxis for deep vein thrombosis (DVT; 5000 U, 3 × daily). OBJECTIVE: To assess the safety and efficacy of LDIVH in aSAH patients. METHODS: We retrospectively analyzed 556 consecutive cases of aSAH patients whose aneurysm was secured by clipping or coiling at a single institution over a 10-yr period, including 233 administered the LDIVH protocol and 323 administered the SQH protocol. Radiological and outcome data were compared between the 2 cohorts using multivariable logistic regression and propensity score-based inverse probability of treatment weighting (IPTW). RESULTS: The unadjusted rate of cerebral infarction in the LDIVH cohort was half that in SQH cohort (9 vs 18%; P = .004). Multivariable logistic regression showed that patients in the LDIVH cohort were significantly less likely than those in the SQH cohort to have DND (odds ratio (OR) 0.53 [95% CI: 0.33, 0.85]) or cerebral infarction (OR 0.40 [95% CI: 0.23, 0.71]). Analysis following IPTW showed similar results. Rates of hemorrhagic complications, heparin-induced thrombocytopenia and DVT were not different between cohorts. CONCLUSION: This cohort comparison analysis suggests that LDIVH infusion may favorably influence the outcome of patients after aSAH. Prospective studies are required to further assess the benefit of LDIVH infusion in patients with aSAH.

BACKGROUND AND PURPOSE: Previous studies in acute ischemic stroke have demonstrated the importance of minimizing delays to endovascular treatment and keeping thrombectomy procedural times at <30–60 minutes. The purpose of this study was to investigate the impact of thrombectomy procedural times on clinical outcomes. MATERIALS AND METHODS: We retrospectively compared 319 patients having undergone thrombectomy according to procedural time (60 minutes) and time from stroke onset to endovascular therapy (≤6 or >6 hours). Clinical characteristics of patients with postprocedural intracranial hemorrhage were also assessed. Logistic regression was used to determine independent predictors of poor outcome at 90 days (mRS ≥3). RESULTS: Greater age (OR, 1.03; 95% CI, 1.01–1.06; P = .016), higher admission NIHSS score (OR, 1.10; 95% CI, 1.04–1.16; P = .001), history of diabetes mellitus (OR, 1.96; 95% CI, 1.05–3.65; P = .034), and postprocedural intracranial hemorrhage were independently associated with greater odds of poor outcome. Modified TICI scale scores of 2c (OR, 0.11; 95% CI, 0.04–0.28; P < .001) and 3 (OR, 0.15; 95% CI, 0.06–0.38; P < .001) were associated with reduced odds of poor outcome. Although not statistically significant on univariate analysis, onset to endovascular therapy of >6 hours was independently associated with increased odds of poor outcome (OR, 2.20; 95% CI, 1.11–4.36; P = .024) in the final multivariate model (area under the curve = 0.820). Procedural time was not independently associated with clinical outcome in the final multivariate model (P > .05). CONCLUSIONS: Thrombectomy procedural times beyond 60 minutes are associated with lower revascularization rates and worse 90-day outcomes. Procedural time itself was not an independent predictor of outcome. While stroke thrombectomy procedures should be performed rapidly, our study emphasizes the significance of achieving revascularization despite the requisite procedural time. However, the potential for revascularization must be weighed against the risks associated with multiple thrombectomy attempts.

BACKGROUND AND PURPOSE: Although covered side branches typically remain patent acutely following Pipeline Embolization Device embolization of intracranial aneurysms, the long-term fate of these vessels remains uncertain. We therefore elected to investigate factors that may influence the long-term patency of these covered side branches. MATERIALS AND METHODS: We retrospectively evaluated the long-term patency of side branches covered by the Pipeline Embolization Device at our institution during treatment of intracranial aneurysms with at least 6 months of conventional angiography follow-up. Procedural and anatomic factors that might influence the fate of covered side branches were explored. RESULTS: One hundred forty-eight Pipeline Embolization Device treatments in 137 patients met the inclusion criteria. In 217 covered side branches, 29 (13.4%) were occluded on follow-up, and 40 (18.4%) were stenotic. All stenoses and occlusions were asymptomatic. In the entire cohort and in the largest subset of ophthalmic arteries, a smaller Pipeline Embolization Device diameter was associated with branch vessel occlusion (P = .001, P = .013). When we considered stenotic and occluded side branches together, smaller Pipeline Embolization Device size (P = .029) and administration of intraprocedural abciximab (P = .03) predicted side branch stenosis/occlusion, while anterior choroidal branch type (P = .003) was a predictor of gross side branch patency. CONCLUSIONS: A smaller Pipeline Embolization Device diameter is associated with delayed side branch stenosis/occlusion following Pipeline Embolization Device treatment, likely due to the higher metal density of smaller caliber devices. Although hemodynamic factors, including the potential for collateral flow, are still paramount in determining the fate of covered side branches, the amount of metal coverage at the side branch orifice also plays an important role.