Subarachnoid Hemorrhage

Aneurysm Rupture ◽

World Federation ◽

Neurogenic Pulmonary Edema ◽

Surgical Clipping ◽

Systemic Complications ◽

Risk Of Rupture ◽

Anterior Communicating Aneurysm

Subarachnoid hemorrhage (SAH) represents a small portion of cerebrovascular disease but a disproportionally large percentage of the morbidity and mortality. The overall prognosis depends on the volume of the initial bleeding, rebleeding, and the degree of delayed cerebral ischemia. The presence of cardiac manifestations and neurogenic pulmonary edema at the initial presentation indicates a higher degree of severity and systemic complications. This review covers the pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes of SAH. Figures show common saccular aneurysm locations, a noncontrast head computed tomographic scan of an SAH, an angiogram and surgical clipping of a broad-based anterior communicating aneurysm, and a three-dimensional reconstruction angiogram of a complex anterior communicating aneurysm with additional imaging of endoscopic stent-assisted coiling of the same aneurysm. Tables list the natural history of unruptured aneurysms and the annual risk of rupture, common clinical features and syndromes related to aneurysm location, the World Federation of Neurologic Surgeons grading system, the Hunt and Hess grading systems, and the Fisher scale. This review contains 4 highly rendered figures, 5 tables, and 144 references. Key words: aneurysm rupture, cerebral aneurysm, cerebral vasospasm, Fisher scale, Glasgow Coma Scale assessment, Hunt and Hess grading criteria, subarachnoid hemorrhage, World Federation of Neurologic Surgeons grading scale Key Advances CT angiography is an emerging technology that has the diagnostic advantage of being non-invasive. The diagnostic accuracy of CTA varies widely and when compared to the standard digital subtraction angiography (DSA) the sensitivity and specificity range from 77% to 100% and 87%-100% respectively. The 2012 AHA guidelines and the 2011 Neurocritical care society (NCS) consensus guidelines recommend that from the time of symptom onset to securing of the aneurysm, the blood pressure be controlled with a titratable agent with a goal systolic blood pressure of less than 160mmHg or a MAP of less than 110mmHg. Cardiac abnormalities are common following acute SAH. Subendocardial ischemia may result from autonomic stimulation from the brain and circulating catecholamine surge, resulting in an abnormal ECG in 50% to 100% of patients with SAH in the acute phase depending on severity. The International Subarachnoid Aneurysm Trial ISAT was a landmark study that looked at aSAH repair comparing surgical clipping with endoscopic coiling and demonstrated a mortality benefit with coiling in the right patient population.

Subarachnoid Hemorrhage

10.2310/im.4707 ◽

2016 ◽

Author(s):

Imoigele P Aisiku

Keyword(s):

Subarachnoid Hemorrhage ◽

Three Dimensional ◽

Aneurysm Rupture ◽

World Federation ◽

Neurogenic Pulmonary Edema ◽

Systemic Complications ◽

Unruptured Aneurysms ◽

Risk Of Rupture ◽

Anterior Communicating Aneurysm

Aneurysmal subarachnoid hemorrhage: current concepts and updates

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20190112 ◽

2019 ◽

Vol 77 (11) ◽

pp. 806-814 ◽

Cited By ~ 1

Author(s):

Carolina Rouanet ◽

Gisele Sampaio Silva

Keyword(s):

Subarachnoid Hemorrhage ◽

Endovascular Coiling ◽

Imaging Features ◽

Surgical Clipping ◽

Systemic Complications ◽

Antifibrinolytic Therapy ◽

Head Computed Tomography ◽

The Ideal

ABSTRACT Aneurysmal subarachnoid hemorrhage is a condition with a considerable incidence variation worldwide. In Brazil, the exact epidemiology of aneurysmal SAH is unknown. The most common presenting symptom is headache, usually described as the worst headache ever felt. Head computed tomography, when performed within six hours of the ictus, has a sensitivity of nearly 100%. It is important to classify the hemorrhage based on clinical and imaging features as a way to standardize communication. Classification also has prognostic value. In order to prevent rebleeding, there still is controversy regarding the ideal blood pressure levels and the use of antifibrinolytic therapy. The importance of definitely securing the aneurysm by endovascular coiling or surgical clipping cannot be overemphasized. Hydrocephalus, seizures, and intracranial pressure should also be managed. Delayed cerebral ischemia is a severe complication that should be prevented and treated aggressively. Systemic complications including cardiac and pulmonary issues, sodium abnormalities, fever, and thromboembolism frequently happen and may have na impact upon prognosis, requiring proper management.

Abstract 192: The Relationship of Platelet-leukocyte Aggregates and Early Brain Injury After Subarachnoid Hemorrhage

Stroke ◽

10.1161/str.48.suppl_1.192 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Jennifer A Frontera ◽

Vladimir Katyshev ◽

Thomas M McIntyre ◽

Fatima A Sehba ◽

Jonathan M Weimer ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Brain Injury ◽

Early Brain Injury ◽

Aneurysm Rupture ◽

Acute Brain Injury ◽

Unruptured Aneurysms ◽

Major Predictor ◽

A Prospective Study ◽

And Control

Introduction: Acute brain injury incurred after aneurysm rupture in subarachnoid hemorrhage (SAH) is a major predictor of poor functional outcome. We hypothesize that platelet-leukocyte aggregates (PLA) form early after SAH and contribute to acute brain injury. Methods: A prospective study of antiplatelet-naive SAH patients and controls (patients with unruptured aneurysms undergoing repair) was conducted from 3/2014-3/2016. Platelet-monocyte, platelet-lymphocyte and platelet-neutrophil aggregates in whole blood were measured with and without exposure to a platelet agonist (Thrombin receptor activating peptide [TRAP]) using flow cytometry. PLA within 24h and averaged over 72h from ictus (prior to the onset of delayed cerebral ischemia/vasospasm) were compared between patients with mild (admission Hunt-Hess [HH] 1-3) versus severe early brain injury (EBI; HH 4-5). Results: We enrolled 60 SAH patients and 13 controls. PLA were significantly lower in those with severe EBI compared to those with mild EBI (Platelet-monocyte-aggregates 36% versus 53%, P=0.011; Platelet-neutrophil-aggregates 15.2 versus 23.1%, P=0.002) within 24h of ictus and prior to aneurysm repair and remained significantly lower over 72h (both P<0.05). Platelet-monocyte, platelet-neutrophil and platelet-lymphocyte aggregates were also significantly lower in those with severe EBI compared to controls (all P<0.05). The ability of platelets to be stimulated/activated by TRAP to form PLA was also lower in severe EBI patients compared to mild EBI and control patients over 72h (platelet-neutrophil-aggregates 79.7, 88.2 and 92.7%, respectively, P=0.003; platelet-lymphocyte aggregates 9.2, 11.0 and 14.6%, respectively, P=0.022), consistent with prior platelet activation/degranulation. Conclusions: PLA are lower, and respond less to stimulation in patients with severe EBI after SAH compared to those with mild EBI and controls. These data suggest that in severe EBI: PLA may form earlier and are cleared, are adherent to endothelium and not shed in the blood, or have migrated into the parenchyma. These hypotheses bear further study.

Deviation from Dynamic and Personalized Optimal Blood Pressure Targets is Associated With Worse Functional Outcomes After Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽

10.1093/neuros/nyz310_186 ◽

2019 ◽

Vol 66 (Supplement_1) ◽

Author(s):

Andrew Silverman ◽

Sreeja Kodali ◽

Sumita Strander ◽

Emily Gilmore ◽

Alexandra Kimmel ◽

...

Keyword(s):

Blood Pressure ◽

Subarachnoid Hemorrhage ◽

Functional Outcome ◽

Functional Outcomes ◽

Near Infrared ◽

Time Correlation ◽

Blood Pressure Targets ◽

Percent Time

Abstract INTRODUCTION Effective blood pressure (BP) management after aneurysmal subarachnoid hemorrhage (aSAH) is critical for maintaining optimal cerebral perfusion and protecting the brain from further injury. How to best manage BP during the early stages of aSAH remains uncertain. In this study, we calculated individualized BP thresholds at which cerebral autoregulation was best preserved. We analyzed how deviating from these limits correlates with functional outcome. METHODS We prospectively enrolled 31 patients with aSAH. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy (NIRS)-derived tissue oxygenation – a surrogate for cerebral blood flow – as well as intracranial pressure (ICP) in response to changes in mean arterial pressure (MAP) using time-correlation analysis. The resulting autoregulatory indices were used to trend BP ranges at which autoregulation was most preserved. The percent time that MAP exceeded limits of autoregulation (LA) was calculated for each patient. Functional outcome was assessed using the modified Rankin Scale (mRS) at discharge and 90 d. Associations with outcome were analyzed using ordinal multivariate logistic regression. RESULTS Personalized LA were computed in all patients (age 57.5, 23F, mean WFNS 2, monitoring time 67.8 h). Optimal BP and LA were calculated on average for 89.5% of the total monitoring period. ICP- and NIRS-derived optimal pressures and LA strongly correlated with one another (P < .0001). Percent time that MAP deviated from LA significantly associated with worse functional outcome at discharge (NIRS P = .001, ICP P = .004) and 90 d (NIRS P = .002, ICP P = .003), adjusting separately for age, WFNS, vasospasm, or delayed cerebral ischemia. CONCLUSION Both invasive (ICP) and non-invasive (NIRS) determination of personalized BP thresholds for aSAH patients is feasible, and these 2 approaches revealed significant collinearity. Exceeding individualized autoregulatory thresholds may increase the risk of poor functional outcomes.

Retrospective review of previous minor leak before major subarachnoid hemorrhage diagnosed by MRI as a predictor of occurrence of symptomatic delayed cerebral ischemia

10.3171/2016.10.jns161964 ◽

2018 ◽

Vol 128 (2) ◽

pp. 499-505 ◽

Cited By ~ 4

Author(s):

Shinri Oda ◽

Masami Shimoda ◽

Akihiro Hirayama ◽

Masaaki Imai ◽

Fuminari Komatsu ◽

...

Keyword(s):

Multivariate Analysis ◽

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Retrospective Review ◽

Diffusion Weighted Imaging ◽

World Federation ◽

Related Factor ◽

Acute Infarction ◽

Time Of Admission

OBJECTIVEThis study attempted to determine whether a previous minor leak correlated with the occurrence of symptomatic delayed cerebral ischemia (sDCI).METHODSThe authors retrospectively evaluated sDCI-related clinical features and findings from MRI, including T1-weighted imaging (T1WI)–FLAIR mismatch at the time of admission, in 151 patients admitted with subarachnoid hemorrhage (SAH) within 48 hours of ictus.RESULTSThe overall incidence of sDCI was 23% (35 of 151 patients). In all subjects, multivariate analysis revealed that World Federation of Neurosurgical Societies Grades II–V, age 70 years or older, presence of rebleeding after admission, a previous minor leak before the major SAH attack as diagnosed by T1WI-FLAIR mismatch, acute infarction on diffusion-weighted imaging, and CT SAH score were significantly associated with occurrence of sDCI. In patients with no previous minor leak before major SAH as diagnosed by T1WI-FLAIR mismatch, the incidence of sDCI was only 7% (7 of 97 patients).CONCLUSIONSA previous minor leak before major SAH as diagnosed by T1WI-FLAIR mismatch represents an important sDCI-related factor. When the analysis was restricted to patients with true acute SAH without a previous minor leak diagnosed by T1WI-FLAIR mismatch, the incidence of sDCI was extremely low.

Aspirin and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

10.3171/jns.1995.82.6.0945 ◽

1995 ◽

Vol 82 (6) ◽

pp. 945-952 ◽

Cited By ~ 82

Author(s):

Seppo Juvela

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Cerebral Infarction ◽

Platelet Function ◽

Aneurysm Rupture ◽

Content Type ◽

Reduced Risk ◽

Fine Print

✓ This follow-up study was designed to evaluate whether the use of aspirin either before or after aneurysm rupture affects the occurrence of delayed cerebral ischemia. Aspirin inhibits platelet function and thromboxane production and has been shown to reduce the risk of various cardiovascular and cerebrovascular ischemic diseases. Following admission, the patients in this study were interviewed regarding their use of aspirin and other medicines prior to and after hemorrhage, and their urine was screened qualitatively for salicylates. Patient outcome and the occurrence of hypodense lesions consistent with cerebral infarction on follow-up computerized tomography (CT) were studied prospectively up to 1 year after hemorrhage. Of 291 patients, 31 (11%) died because of the initial hemorrhage and 18 (6%) died due to rebleeding within 4 days after hemorrhage. Of the remaining 242 patients, 90 (37%) had delayed cerebral ischemia, which caused a permanent neurological deficit or death in 54 patients (22%). Of 195 patients undergoing follow-up CT, 85 (44%) had cerebral infarction that was not seen on the CT scan obtained on admission. Those who had salicylates in the urine on admission had a relative risk of 0.40 (95% confidence interval (CI), 0.15 to 1.10) of delayed ischemia with fixed deficit and a risk of 0.40 (95% CI, 0.18 to 0.93) of cerebral infarction compared with patients who did not have salicylates in their urine. This reduced risk of ischemic complications with aspirin use was restricted to those patients who used aspirin before hemorrhage, when the risk of ischemia was 0.21 (95% CI, 0.03 to 1.63) and the risk of infarct was 0.18 (95% CI, 0.04 to 0.84) compared with those who had not used aspirin. The reduced risk of cerebral infarction remained significant after adjustment for several potential confounding factors (adjusted risk 0.19; 95% CI, 0.04 to 0.89). These observations suggest that platelet function at the time of subarachnoid hemorrhage may be associated with delayed cerebral ischemia after aneurysm rupture.

Prognosis Value of Plasma S100B Protein Levels after Subarachnoid Aneurysmal Hemorrhage

Anesthesiology ◽

10.1097/00000542-200604000-00008 ◽

2006 ◽

Vol 104 (4) ◽

pp. 658-666 ◽

Cited By ~ 52

Author(s):

Nicolas Weiss ◽

Paola Sanchez-Peña ◽

Sabine Roche ◽

Jean L. Beaudeux ◽

Chantal Colonne ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Odds Ratio ◽

Time Course ◽

Neuronal Damage ◽

Intensive Care Unit Discharge ◽

World Federation ◽

Surgical Clipping ◽

Blood Concentrations ◽

Protein Levels ◽

High World

Background S100B has been described as a biologic marker of neuronal damage. The purpose of this study was to assess its prognostic value in patients with subarachnoid aneurysmal hemorrhage. Methods Seventy-four patients (32 men and 42 women; age, 48 +/- 11 yr) admitted within 48 h after subarachnoid hemorrhage onset and treated by surgical clipping or coiling within 2 days after admission were included. World Federation of Neurological Surgeons, Fisher, and Glasgow outcome scores at intensive care unit discharge and at 6 months were evaluated. Blood concentrations of S100B were determined at admission and daily up to day 8. Results The time course of S100B was increased in patients with high World Federation of Neurological Surgeons and Fisher scores. Patients who underwent surgical clipping had an S100B time course longer than that of those who underwent coiling. This difference remained true after stratification for World Federation of Neurological Surgeons and Fisher scores. The threshold of mean daily value of S100B predicting a poor outcome at 6 months was 0.4 microg/l (sensitivity = 0.50 [95% confidence interval (CI), 0.29-0.71], specificity = 0.87[corrected] [95% CI, 0.76-0.95]). In multivariate analysis, high World Federation of Neurological Surgeons score (odds ratio = 9.5 [95% CI, 3.1-29.4]), mean daily S100B value above 0.4 microg/l (odds ratio = 7.3 [95% CI, 2.3-23.6]), and age (odds ratio = 1.08 per year [95% CI, 1.01-1.15]) were independent predictors of a poor 6-month outcome (Glasgow outcome score 1-3). Conclusion Mean daily value of S100B assessed during the first 8 days is a prognostic tool complementary to initial clinical evaluation in subarachnoid hemorrhage patients.

The safety of vasopressor-induced hypertension in subarachnoid hemorrhage patients with coexisting unruptured, unprotected intracranial aneurysms

10.3171/2014.12.jns141201 ◽

2015 ◽

Vol 123 (4) ◽

pp. 862-871 ◽

Cited By ~ 12

Author(s):

Matthew R. Reynolds ◽

Robert T. Buckley ◽

Santoshi S. Indrakanti ◽

Ali H. Turkmani ◽

Gerald Oh ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Intracranial Aneurysms ◽

Patient Characteristics ◽

Aneurysm Rupture ◽

Unruptured Aneurysms ◽

Size Number ◽

Days Of Therapy ◽

Induced Hypertension

OBJECT Vasopressor-induced hypertension (VIH) is an established treatment for patients with aneurysmal subarachnoid hemorrhage (SAH) who develop vasospasm and delayed cerebral ischemia (DCI). However, the safety of VIH in patients with coincident, unruptured, unprotected intracranial aneurysms is uncertain. METHODS This retrospective multiinstitutional study identified 1) patients with aneurysmal SAH and 1 or more unruptured, unprotected aneurysms who required VIH therapy (VIH group), and 2) patients with aneurysmal SAH and 1 or more unruptured, unprotected aneurysms who did not require VIH therapy (non-VIH group). All patients had previously undergone surgical or endovascular treatment for the presumed ruptured aneurysm. Comparisons between the VIH and non-VIH patients were made in terms of the patient characteristics, clinical and radiographic severity of SAH, total number of aneurysms, number of ruptured/unruptured aneurysms, aneurysm location/size, number of unruptured and unprotected aneurysms during VIH, severity of vasospasm, degree of hypervolemia, and degree and duration of VIH therapy. RESULTS For the VIH group (n = 176), 484 aneurysms were diagnosed, 231 aneurysms were treated, and 253 unruptured aneurysms were left unprotected during 1293 total days of VIH therapy (5.12 total years of VIH therapy for unruptured, unprotected aneurysms). For the non-VIH group (n = 73), 207 aneurysms were diagnosed, 93 aneurysms were treated, and 114 unruptured aneurysms were left unprotected. For the VIH and non-VIH groups, the mean sizes of the ruptured (7.2 ± 0.3 vs 7.8 ± 0.6 mm, respectively; p = 0.27) and unruptured (3.4 ± 0.2 vs 3.2 ± 0.2 mm, respectively; p = 0.40) aneurysms did not differ. The authors observed 1 new SAH from a previously unruptured, unprotected aneurysm in each group (1 of 176 vs 1 of 73 patients; p = 0.50). Baseline patient characteristics and comorbidities were similar between groups. While the degree of hypervolemia was similar between the VIH and non-VIH patients (fluid balance over the first 10 days of therapy: 3146.2 ± 296.4 vs 2910.5 ± 450.7 ml, respectively; p = 0.67), VIH resulted in a significant increase in mean arterial pressure (mean increase over the first 10 days of therapy relative to baseline: 125.1% ± 1.0% vs 98.2% ± 1.2%, respectively; p < 0.01) and systolic blood pressure (125.6% ± 1.1% vs. 104.1% ± 5.2%, respectively; p < 0.01). CONCLUSIONS For small, unruptured, unprotected intracranial aneurysms in SAH patients, the frequency of aneurysm rupture during VIH therapy is rare. The authors do not recommend withholding VIH therapy from these patients.

Does intrathecal nicardipine for cerebral vasospasm following subarachnoid hemorrhage correlate with reduced delayed cerebral ischemia? A retrospective propensity score–based analysis

10.3171/2020.12.jns203673 ◽

2021 ◽

pp. 1-10

Author(s):

Ofer Sadan ◽

Hannah Waddel ◽

Reneé Moore ◽

Chen Feng ◽

Yajun Mei ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Propensity Score ◽

Functional Outcome ◽

Cerebral Vasospasm ◽

University Hospital ◽

World Federation ◽

Ventriculoperitoneal Shunting ◽

Fisher Grade

OBJECTIVE Cerebral vasospasm and delayed cerebral ischemia (DCI) contribute to poor outcome following subarachnoid hemorrhage (SAH). With the paucity of effective treatments, the authors describe their experience with intrathecal (IT) nicardipine for this indication. METHODS Patients admitted to the Emory University Hospital neuroscience ICU between 2012 and 2017 with nontraumatic SAH, either aneurysmal or idiopathic, were included in the analysis. Using a propensity-score model, this patient cohort was compared to patients in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository who did not receive IT nicardipine. The primary outcome was DCI. Secondary outcomes were long-term functional outcome and adverse events. RESULTS The analysis included 1351 patients, 422 of whom were diagnosed with cerebral vasospasm and treated with IT nicardipine. When compared with patients with no vasospasm (n = 859), the treated group was significantly younger (mean age 51.1 ± 12.4 years vs 56.7 ± 14.1 years, p < 0.001), had a higher World Federation of Neurosurgical Societies score and modified Fisher grade, and were more likely to undergo clipping of the ruptured aneurysm as compared to endovascular treatment (30.3% vs 11.3%, p < 0.001). Treatment with IT nicardipine decreased the daily mean transcranial Doppler velocities in 77.3% of the treated patients. When compared to patients not receiving IT nicardipine, treatment was not associated with an increased rate of bacterial ventriculitis (3.1% vs 2.7%, p > 0.1), yet higher rates of ventriculoperitoneal shunting were noted (19.9% vs 8.8%, p < 0.01). In a propensity score comparison to the SAHIT database, the odds ratio (OR) to develop DCI with IT nicardipine treatment was 0.61 (95% confidence interval [CI] 0.44–0.84), and the OR to have a favorable functional outcome (modified Rankin Scale score ≤ 2) was 2.17 (95% CI 1.61–2.91). CONCLUSIONS IT nicardipine was associated with improved outcome and reduced DCI compared with propensity-matched controls. There was an increased need for permanent CSF diversion but no other safety issues. These data should be considered when selecting medications and treatments to study in future randomized controlled clinical trials for SAH.

ANGPT1 methylation and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage patients

Epigenetics Communications ◽

10.1186/s43682-021-00001-7 ◽

2021 ◽

Vol 1 (1) ◽

Author(s):

Dongjing Liu ◽

Annie I. Arockiaraj ◽

John R. Shaffer ◽

Samuel M. Poloyac ◽

Paula R. Sherwood ◽

...

Keyword(s):

Dna Methylation ◽

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Pooled Analysis ◽

Aneurysm Rupture ◽

Cpg Sites ◽

Significance Threshold ◽

Post Hoc

Abstract Background Delayed cerebral ischemia (DCI) is a common secondary complication and an important cause of disability and mortality among patients who survive aneurysmal subarachnoid hemorrhage (aSAH). Knowledge on DCI pathogenesis, risk factors, and biomarkers are essential for early detection and improved prognosis. To investigate the role of DNA methylation in DCI risk, we conducted an epigenome-wide association study (EWAS) in 68 patients followed up to 1 year after the initial aneurysm rupture. Blood samples were collected within 48 h post hemorrhage and used for DNA methylation profiling at ~ 450k CpG sites. A separate cohort of 175 patients was sequenced for the top CpG sites from the discovery analysis for a replication of the EWAS findings. Results EWAS did not identify any epigenome-wide significant CpGs. The top signal, cg18031596, was annotated to ANGPT1, a gene with critical functions in angiogenesis after vascular injury. Post hoc power calculations indicated a well-powered discovery analysis for cg18031596. Analysis of the replication cohort showed that four out of the five CpG sites sequenced at the ANGPT1 locus passed a Bonferroni-adjusted significance threshold. In a pooled analysis of the entire sample, three out of five yielded a significant p-value, and the top association signal (p-value = 0.004) was seen for a CpG that was not originally measured in the discovery EWAS. However, four ANGPT1 CpG sites had an opposite effect direction in the replication analysis compared to the discovery EWAS, marking a failure of replication. We carefully examined this observed flip in directions and propose several possible explanations in addition to that it was a random chance that ANGPT1 ranked at the top in the discovery EWAS. Conclusions We failed to demonstrate a significant and consistent effect of ANGPT1 methylation in DCI risk in two cohorts. Though the replication attempt to weaken the overall support of this gene, given its relevant function and top rank of significance in the EWAS, our results call for future studies of larger aSAH cohorts to determine its relevance for the occurrence of DCI.