Subarachnoid Hemorrhage

ImportanceNontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure.ObjectiveTo estimate the worldwide burden of SAH.Design, setting, and participantsBased on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021.ExposuresSAH and 14 modifiable risk factors.Main outcomes and measuresAbsolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor-specific population attributable fractions (PAFs).ResultsIn 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution.Conclusions and relevanceAlthough the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

ImportanceEmergency department (ED) triage may impact timeliness of care for high-risk conditions.ObjectiveTo determine the association of ED undertriage with delays in care for patients with subarachnoid hemorrhage (SAH), aortic dissection (AD), and ST-elevation myocardial infarction (STEMI).Design, setting, and participantsThis retrospective cohort study included adult ED patients diagnosed with SAH, AD, or STEMI from January 1, 2016, to December 31, 2020, from a multicenter, community-based health care delivery system. Data analysis were completed in March 2023 to October 2024.ExposureUndertriage vs correct triage, defined by operational measures of mistriage.Main outcomes and measuresUsing a lognormal distribution, the outcomes of interest for patients with SAH and AD were adjusted median time to noncontrast computed tomography (CT) (head CT for patients with SAH, chest CT for patients with AD), antihypertensive medication orders (SAH), and β-blocker orders (AD), and ED length of stay (LOS). For patients with STEMI, outcomes of interest were adjusted median time to electrocardiogram (ECG) and troponin orders.ResultsA total of 5929 patients (median [IQR] age, 63.0 [54.0 to 73.0] years; 3876 [65.4%] male) were identified, including 915 with SAH, 480 with AD, and 4534 with STEMI. There were 1129 Asian patients (19.0%), 553 Black patients (9.3%), 889 Hispanic patients (15.0%), and 2906 non-Hispanic White patients (49.0%). Overall, 2175 patients (36.7%) were undertriaged. For patients with SAH, the lognormal estimate for delay in time to head CT was 0.2 (95% CI, 0.0-0.3), or a delay of 2.4 minutes, and for antihypertensive orders, the lognormal estimate was 4.8 (95% CI, 3.6-5.9), or a delay of 33.3 minutes; the lognormal estimate for ED LOS was 0.1 (95% CI, 0.0-0.1), or 7.7 minutes longer. For patients with AD, the lognormal estimate for delays were 0.2 (95% CI, 0.0-0.4), or 8.9 minutes, for chest CT and 0.5 (95% CI, 0.2-0.7), or 17.6 minutes, for β-blocker orders, and ED LOS was 0.2 (95% CI, 0.1-0.3), or 64 minutes longer. For patients with STEMI, differences in time to ECG and troponin orders were not statistically significant, at less than 1 minute, comparing correctly and undertriaged patients.Conclusions and relevanceIn this cohort study of patients diagnosed with SAH, AD, or STEMI, ED undertriage was associated with small but significant delays in key diagnostic and therapeutic orders for patients with SAH and AD but not for patients with STEMI.

Subarachnoid hemorrhage (SAH) is a frequently encountered critical emergency characterized by the rupturing of an unhealthy blood vessel, resulting in high mortality and disability rates. Alterations in the neurovascular unit (NVU) are closely related to the pathogenesis of SAH. Microglia, the primary innate immune cells in the brain, and astrocytes, the most abundant cells in the brain, both play crucial roles in the response to SAH-associated cerebral injuries. Recently, the crosstalk between these two cells in the pathology and treatment of central nervous system (CNS) diseases, including SAH, has been revealed. Following acute brain insult, activated microglia and astrocytes can further activate each other, contributing to amplified neuroinflammatory reactions and thus inducing secondary brain injury. This review addresses the pathophysiological mechanisms of microglia and astrocytes in SAH, including neuroinflammation, neuronal damage, blood-brain barrier (BBB) disruption, vasospasm, and hematoma clearance. In addition, the newly identified therapeutic strategies against SAH by regulating astrocytes-microglia crosstalk through targeting damage-associated molecular patterns (DAMPs), immune mediators, and their receptors are also discussed. A thorough comprehension of microglia-astrocyte communication could provide novel ideas for future research and treatment of SAH.

More than half of subarachnoid hemorrhage (SAH) survivors develop delayed cognitive dysfunction, but the underlying mechanisms remain elusive. This study investigated the role of meningeal lymphatic vessels (mLVs) in this complication by examining their structural integrity, drainage capacity, and association with cognitive deficits post-SAH. In adult male C57BL/6J mice in which SAH was induced by intracisternal injection of autologous blood, spatial learning and memory, and hippocampal CA1 neuronal activity were impaired as early as 1 month post-surgery, with a marked exacerbation of these deficits at 2 months. SAH induced mLV fragmentation and atrophy, subsequent cerebrospinal and interstitial fluid drainage impairment, metabolite accumulation, and ultimately delayed cognitive dysfunction. Notably, lymphatic vessel ablation exacerbated these pathologies. In vitro experiments confirmed that vascular endothelial growth factor C (VEGF-C) reduced oxyhemoglobin-induced lymphatic endothelial cell apoptosis. Furthermore, in vivo studies demonstrated that VEGF-C therapy inhibited amyloid-β (Aβ) deposition in the hippocampal CA1 region and ameliorated cognitive dysfunction. Additional studies revealed that VEGF-C's protective effect on mLVs may be mediated via PI3K-AKT pathway activation. Collectively, these findings indicate that disrupted mLV integrity and drainage contribute to post-SAH cognitive impairment. Activation of VEGF-C-mediated PI3K-AKT signaling may preserve mLV function and represent a potential therapeutic strategy for preventing delayed cognitive impairment after SAH.