Novel Subgroups in Subarachnoid Hemorrhage and Their Association With Outcomes—A Systematic Review and Meta-Regression

Abstract

Background and Purpose: Subarachnoid hemorrhage (SAH) has long been classified into two main forms, aneurysmal SAH (aSAH) and non-aneurysmal SAH (naSAH), but the related risk factors for aSAH and naSAH are heterogeneous. Our objective was to determine the risk factors for SAH of known or unknown origin with respect to diagnostic evaluation in a large patient cohort. We sought to determine whether our classification system can further predict middle long-term stroke and death.Methods: We performed a systematic review and meta-analysis to identify risk factors for each SAH subtype. The discovery phase analyzed 11 risk factors from case studies in the literature. Kruskal-Wallis, Cox regression, logistic regression, and Kaplan-Meier analyses were used to compare the two groups.Results: A total of 14,904 (34.53%) male and 22,801 (52.84%) female patients were eligible for this study. At a median follow-up of 45.6 months, the 5-years overall survival was 97.768% (95% CI: 0.259–0.292) for aSAH patients and 87.904% (95% CI: 1.459–1.643) for naSAH patients. The 10-years survival rate was 93.870% (95% CI: 2.075–3.086) and 78.115% (95% CI: 2.810–3.156), respectively. Multi-risk factor subgroups showed significant intergroup differences. We identified eight risk factors (drugs, trauma, neoplastic, vessels lesion, inflammatory lesion, blood disease, aneurysm, peri-mesencephalic hemorrhage) using logistic regression, which were optimally differentiated among the aSAH [aSAH-S (AUC: 1), a-d-SAH (AUC: 0.9998), aSAH-T (AUC: 0.9199), aSAH-N (AUC: 0.9433), aSAH-V (AUC: 1), aSAH-I (AUC: 0.9954), a-bd-SAH (AUC: 0.9955)] and naSAH [na-pmSAH (AUC: 0.9979), na-ni-ivl-SAH (AUC: 1), na-t-SAH (AUC: 0.9997), na-ne-SAH (AUC: 0.9475), na-d-SAH (AUC: 0.7676)] subgroups. These models were applied in a parallel cohort, showing eight risk factors plus survival rates to predict the prognosis of SAH.Conclusions: The classification of risk factors related to aSAH and naSAH is helpful in the diagnosis and prediction of the prognosis of aSAH and naSAH patients. Further validation is needed in future clinical applications.

Systemic Inflammatory Response in Spontaneous Subarachnoid Hemorrhage from Aneurysmal Rupture versus Subarachnoid Hemorrhage of Unknown Origin

“…Using the G*Power software (v3.1.9.6, University of Kiel, Germany) for calculating the a priori sample size power, for repeated measurement analysis, assuming an alpha error probability of 0.05, a power of 0.80, and two independent groups (aSAH and smSAH), with 6 different time points, and no information about correlations among the serial measurements, 26 expecting a small-to-medium effect size (with f ranging from 0.20 to 0.25) based on the existing literature, 10 the overall minimum sample size requested was found to vary between 24 and 36, with the minimum requested number of smSAH patients ranging from 4 to 5, assuming a 15% prevalence rate. Furthermore, post-hoc power analysis of the sample size demonstrated the statistical robustness of our study.…”

“… 5 , 6 Although even in these patients subarachnoid blood is not harmless, and recent studies have shown possible vasospasm, re-bleeding, hydrocephalus, seizure, cognitive impairment, and depression among sequelae, 7–9 the prognosis of smSAH patients is much better when compared with aneurysmal SAH (aSAH). 10 …”

Current status of perimesencephalic non-aneurysmal subarachnoid hemorrhage

“…Patients with PNSAH have a nearly normal life expectancy, and no restrictions should be imposed on these patients. In a systematic review by Wang et al ( 85 ) patients with PNSAH showed a 13-month survival rate of 97.2% and a 30-month survival rate of 98.6%. In Greebe et al's ( 84 ) report of PNSAH consisting of 160 patients, with a total number of 1,213 patient-years, no new SAH occurred, and 11 patients died; however, none of the deaths were direct consequences of PNSAH, and patients have a normal life expectancy.…”

The Role of Early Cerebral Edema and Hematoma assessment in Aneurysmal Subarachnoid Hemorrhage (a-SAH) in predicting Structural Brain Abnormalities in Cognitive Impairments

“…Clinical variables were selected based on previous recommendations which included general risk factors, baseline demographic data, and vascular risk factor data 1 . This included gender, age, blood pressure, lipid profile, glucose levels, smoking history, surgical time, aneurysm location and size, initial severity of bleed, clinical markers of EBI, SEBES scale 21 , Hunt-Hess scale 22 , modified Fisher grade, and Glasgow Coma Scale (GCS) at time of admission, and MoCA and MMSE at 2-months post-discharge (Details in online supplemental materials, Clinical Variables).…”

“…The latest delineation of subgroups within the subarachnoid space provides a theoretical basis for more accurate diagnosis and treatment of subarachnoid hemorrhage (SAH) 1 . Specifically, aneurysmal subarachnoid hemorrhage (a-SAH) is a subtype of hemorrhage stroke associated with high morbidity and mortality, constituting a significant cause of neurological disease 1,2 . Common complications following a-SAH include early brain injury (EBI), symptomatic vasospasm, brain edema, delayed cerebral ischemia (DCI), delayed deficits, and cognitive impairments (CI) 3,4,5 .…”