Subarachnoid Hemorrhage

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.

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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 ◽

Delayed Cerebral Ischemia ◽

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.

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

Journal of Neurosurgery ◽

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 ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

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.

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DCI after Aneurysmal Subarachnoid Hemorrhage Is Related to the Expression of MFG-E8

BioMed Research International ◽

10.1155/2021/6568477 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Xianjun Chen ◽

Yong’an Jiang ◽

Jiayu Liu ◽

Changfeng Wang ◽

Dengfeng Wan ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Milk Fat ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Characteristic Curve ◽

Delayed Cerebral Ischemia ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

World Federation ◽

Case Group ◽

Unruptured Aneurysms

Objective. To explore the predictive value of milk fat globule epidermal growth factor 8 (MFG-E8) in the occurrence of delayed cerebral ischemia (DCI) after an aneurysmal subarachnoid hemorrhage (aSAH). Methods. We recruited 32 patients with aSAH as the case group and 24 patients with unruptured aneurysms as the control group. Serum MFG-E8 levels were measured by western blot and enzyme-linked immunosorbent assay. We analyzed the relationship between MFG-E8 levels and the risk of DCI. Results. The levels of serum MFG-E8 in the case group ( mean = 11160.9 pg/mL) were significantly higher than those in the control group ( mean = 3081.0 pg/mL, p < 0.001 ). MFG-E8 levels highly correlated with the World Federation of Neurosurgical Societies (WFNS) and modified Fisher scores ( r = − 0.691 and − 0.767 , respectively, p < 0.001 ). In addition, MFG-E8 levels in patients with DCI ( 5882.7 ± 3162.4 pg/mL) were notably higher than those in patients without DCI ( 15818.2 ± 3771.6 pg/mL, p < 0.001 ). A receiver operating characteristic curve showed that the occurrence of DCI could effectively be predicted by MFG-E8 (area under the curve = 0.976 , 95 % CI = 0.850 – 1.000 ). Kaplan–Meier survival analysis showed a remarkable decrease in the incidence of DCI in case group individuals with high levels of MFG-E8 (≥11160.9 pg/mL, p < 0.001 ). Conclusion. MFG-E8 may be a useful predictive marker for DCI after an aSAH and could be a promising surrogate end point.

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

Journal of Neurosurgery ◽

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 ◽

Delayed Cerebral Ischemia ◽

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.

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Aspirin and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

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 ◽

Delayed Cerebral Ischemia ◽

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.

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RISK OF ANEURYSMAL RUPTURE

Neurosurgery ◽

10.1227/01.neu.0000318160.59848.46 ◽

2008 ◽

Vol 62 (4) ◽

pp. 767-775 ◽

Cited By ~ 24

Author(s):

Tomotaka Ohshima ◽

Shigeru Miyachi ◽

Ken-ichi Hattori ◽

Ichiro Takahashi ◽

Katsuya Ishii ◽

...

Keyword(s):

Flow Separation ◽

Three Dimensional ◽

Flow Simulation ◽

Type A ◽

Patient Specific ◽

Parent Artery ◽

Type B ◽

Unruptured Aneurysms ◽

Risk Of Rupture ◽

Type C

Abstract OBJECTIVE The aim of the present study was to clarify the risk of rupture in terminal-type intracranial aneurysms using computational flow simulation analysis. METHODS First, idealized three-dimensional aneurysmal models were built from a solid voxel on the computer. We focused on round terminal-type aneurysms with the positioning of the neck orifice set according to the following three patterns in relationship to the axis of the parent artery: the Type-A neck orifice was positioned directly in line with the flow of the parent artery; the Type-B neck orifice was shifted 1.5 mm offline toward the unilateral branch; and the Type-C neck orifice was shifted 3 mm offline. Computational flow simulations were applied with Fujitsu α-Flow software (Fujitusu, Tokyo, Japan). We analyzed flow patterns using modified patient-specific models. We also investigated actual clinical situations to evaluate the differences in neck-orifice positioning between 20 ruptured aneurysms and 26 unruptured ones using three-dimensional angiograms. RESULTS The Type-A neck orifice showed completely symmetrical stream lines in the aneurysm, whereas the Type-C orifice showed a clear round circulation. The Type-B neck orifice, on the other hand, exhibited intra-aneurysmal flow separation. The clinical research demonstrated that Type-B aneurysms were more likely to be found in the ruptured group (P < 0.05). CONCLUSION Flow separation, recognized as one of the causes of intimal injury, could be observed only in Type-B aneurysms, a result that corresponded well with our clinical experience. From the flow-dynamics point of view, this positioning of the neck orifice may be one of the risk factors most likely to induce the rupture of unruptured aneurysms.

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

Journal of Neurosurgery ◽

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 ◽

Delayed Cerebral Ischemia ◽

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.

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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 ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed 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.

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Treatment of Asymptomatic Unruptured Intracranial Aneurysms

Interventional Neuroradiology ◽

10.1177/15910199010070s109 ◽

2001 ◽

Vol 7 (1_suppl) ◽

pp. 61-64

Author(s):

S. Hirai ◽

J. Ono ◽

M. Odaki ◽

T. Serizawa ◽

M. Sato ◽

...

Keyword(s):

Decision Analysis ◽

Conservative Management ◽

Intracranial Aneurysms ◽

Clinical Decision ◽

Systemic Complications ◽

Unruptured Aneurysms ◽

Rupture Rate ◽

Preventive Surgery ◽

Unruptured Intracranial Aneurysms ◽

Risk Of Rupture

The indication of preventive surgery for patients who harbor asymptomatic unruptured intracranial aneurysms remains controversial. To evaluate the benefit of this treatment, we investigated the management outcome in 128 patients with 157 unruptured aneurysms. Surgery was planned in patients 70 years old or younger without serious systemic complications. A total of 77 patients underwent surgery including four endovascular interventions, and conservative management was chosen in 51 patients. There was no mortality and 6.5% morbidity as postoperative results, and no complication was found after endovascular treatment. Among the patients in conservative management, four patients suffered from subsequent rupture during the total follow-up period of 148 person-years. The annual rupture rate was estimated at 2.7%. According to the clinical decision analysis based on our data, preventive surgery is beneficial for a Japanese 70 years old or younger. However, the expected utility decreases if the rupture rate is set at 0.5% or 0.05%, posing a doubt about the benefit of the surgery. Decision analysis provides an aid for logical and objective choice in the management of unruptured aneurysms. The actual risk of rupture has a major impact on decision making in therapeutic strategy.

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