Increased risk of delayed cerebral ischemia in subarachnoid hemorrhage patients with additional intracerebral hematoma

OBJECTIVE Delayed cerebral ischemia (DCI) has a major impact on the outcome of patients suffering from aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to assess the influence of an additional intracerebral hematoma (ICH) on the occurrence of DCI. METHODS The authors conducted a single-center retrospective analysis of cases of SAH involving patients treated between 2006 and 2011. Patients who died or were transferred to another institution within 10 days after SAH without the occurrence of DCI were excluded from the analysis. RESULTS Additional ICH was present in 123 (24.4%) of 504 included patients (66.7% female). ICH was classified as frontal in 72 patients, temporal in 24, and perisylvian in 27. DCI occurred in 183 patients (36.3%). A total of 59 (32.2%) of these 183 patients presented with additional ICH, compared with 64 (19.9%) of the 321 without DCI (p = 0.002). In addition, DCI was detected significantly more frequently in patients with higher World Federation of Neurosurgical Societies (WFNS) grades. The authors compared the original and modified Fisher Scales with respect to the occurrence of DCI. The modified Fisher Scale (mFS) was superior to the original Fisher Scale (oFS) in predicting DCI. Furthermore, they suggest a new classification based on the mFS, which demonstrates the impact of additional ICH on the occurrence of DCI. After the different scales were corrected for age, sex, WFNS score, and aneurysm site, the oFS no longer was predictive for the occurrence of DCI, while the new scale demonstrated a superior capacity for prediction as compared with the mFS. CONCLUSIONS Additional ICH was associated with an increased risk of DCI in this study. Furthermore, adding the presence or absence of ICH to the mFS improved the identification of patients at the highest risk for the development of DCI. Thus, a simple adjustment of the mFS might help to identify patients at high risk for DCI.

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Effects of post-interventional antiplatelet therapy on angiographic vasospasm, delayed cerebral ischemia, and clinical outcome after aneurysmal subarachnoid hemorrhage: a single-center experience

Neurosurgical Review ◽

10.1007/s10143-021-01477-6 ◽

2021 ◽

Author(s):

Claudia Ditz ◽

Björn Machner ◽

Hannes Schacht ◽

Alexander Neumann ◽

Peter Schramm ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Functional Outcome ◽

Antiplatelet Therapy ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Control Group ◽

Lesion Volume ◽

Single Center ◽

Single Center Experience

AbstractPlatelet activation has been postulated to be involved in the pathogenesis of delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to investigate potentially beneficial effects of antiplatelet therapy (APT) on angiographic CVS, DCI-related infarction and functional outcome in endovascularly treated aSAH patients. Retrospective single-center analysis of aSAH patients treated by endovascular aneurysm obliteration. Based on the post-interventional medical regime, patients were assigned to either an APT group or a control group not receiving APT. A subgroup analysis separately investigated those APT patients with aspirin monotherapy (MAPT) and those receiving dual treatment (aspirin plus clopidogrel, DAPT). Clinical and radiological characteristics were compared between groups. Possible predictors for angiographic CVS, DCI-related infarction, and an unfavorable functional outcome (modified Rankin scale ≥ 3) were analyzed. Of 160 patients, 85 (53%) had received APT (n = 29 MAPT, n = 56 DAPT). APT was independently associated with a lower incidence of an unfavorable functional outcome (OR 0.40 [0.19–0.87], P = 0.021) after 3 months. APT did not reduce the incidence of angiographic CVS or DCI-related infarction. The pattern of angiographic CVS or DCI-related infarction as well as the rate of intracranial hemorrhage did not differ between groups. However, the lesion volume of DCI-related infarctions was significantly reduced in the DAPT subgroup (P = 0.011). Post-interventional APT in endovascularly treated aSAH patients is associated with better functional outcome at 3 months. The beneficial effect of APT might be mediated by reduction of the size of DCI-related infarctions.

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Abstract W MP39: SSRI/SNRI Use Is Not Associated With Increased Risk Of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Stroke ◽

10.1161/str.46.suppl_1.wmp39 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Jimmy Young ◽

Tarun Singh ◽

Jennifer Fugate ◽

Alejandro Rabinstein

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Reuptake Inhibitor ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Multivariate Logistic Regression Analysis ◽

Fisher Score ◽

Symptomatic Vasospasm ◽

Increased Risk ◽

Norepinephrine Reuptake Inhibitor

Objective: To determine the effect of Selective Serotonin Reuptake Inhibitor (SSRI)/Selective Norepinephrine Reuptake Inhibitor (SNRI) use prior to or during admission for aneurysmal subarachnoid hemorrhage (aSAH) on the risk of symptomatic vasospasm and diffuse cerebral ischemia (DCI). Methods: Review of electronic records at Mayo Clinic, Rochester from Jan. 2001 to Dec. 2013 of consecutive patients with aSAH. The variables collected and analyzed were: age, sex, active smoking, transfusion, modified Fisher score, WFNS grade, and outcome at discharge. Multivariate logistic regression analysis was used to evaluate factors associated with DCI, symptomatic vasospasm, and poor outcome (modified Rankin score 3-6) within 1 year. Results: 583 [females 367 (63%)] patients with a median age of 55 (47-65) years were admitted with aSAH during the study period. WFNS at nadir was IV-V in 243 (41.6%) and modified Fisher score was 3-4 in 438 (75.2%). Eighty one (14.6%) patients were taking SSRI or SNRI prior to admission and these medications were continued in all of them. Symptomatic vasospasm was present in 154 (27.7%), radiological infarction in 172(29.5%), and DCI in 250(42.9%) patients. SSRI/SNRI use was not associated with the occurrence of DCI (p=0.458), symptomatic vasospasm (p=0.097), radiological infarction (p=0.972), or poor functional outcome (p=0.376). Conclusions: The use of SSRI/SNRI prior to admission and/or during hospitalization in patients with aSAH was not associated with symptomatic vasospasm or DCI.

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Ultra-early angiographic vasospasm associated with delayed cerebral ischemia and infarction following aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/2016.2.jns151939 ◽

2017 ◽

Vol 126 (5) ◽

pp. 1545-1551 ◽

Cited By ~ 8

Author(s):

Fawaz Al-Mufti ◽

David Roh ◽

Shouri Lahiri ◽

Emma Meyers ◽

Jens Witsch ◽

...

Keyword(s):

Logistic Regression ◽

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Cerebral Infarction ◽

Functional Outcome ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Angiographic Vasospasm ◽

Increased Risk ◽

Address Data

OBJECTIVEThe clinical significance of cerebral ultra-early angiographic vasospasm (UEAV), defined as cerebral arterial narrowing within the first 48 hours of aneurysmal subarachnoid hemorrhage (aSAH), remains poorly characterized. The authors sought to determine its frequency, predictors, and impact on functional outcome.METHODSThe authors prospectively studied UEAV in a cohort of 1286 consecutively admitted patients with aSAH between August 1996 and June 2013. Admission clinical, radiographic, and acute clinical course information was documented during patient hospitalization. Functional outcome was assessed at 3 months using the modified Rankin Scale. Logistic regression and Cox proportional hazards models were generated to assess predictors of UEAV and its relationship to delayed cerebral ischemia (DCI) and outcome. Multiple imputation methods were used to address data lost to follow-up.RESULTSThe cohort incidence rate of UEAV was 4.6%. Multivariable logistic regression analysis revealed that younger age, sentinel bleed, and poor admission clinical grade were significantly associated with UEAV. Patients with UEAV had a 2-fold increased risk of DCI (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.4–3.9, p = 0.002) and cerebral infarction (OR 2.0, 95% CI 1.0–3.9, p = 0.04), after adjusting for known predictors. Excluding patients who experienced sentinel bleeding did not change this effect. Patients with UEAV also had a significantly higher hazard for DCI in a multivariable model. UEAV was not found to be significantly associated with poor functional outcome (OR 0.8, 95% CI 0.4–1.6, p = 0.5).CONCLUSIONSUEAV may be less frequent than has been reported previously. Patients who exhibit UEAV are at higher risk for refractory DCI that results in cerebral infarction. These patients may benefit from earlier monitoring for signs of DCI and more aggressive treatment. Further study is needed to determine the long-term functional significance of UEAV.

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Comparison of Initial Vasopressors Used for Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage

Cerebrovascular Diseases ◽

10.1159/000458536 ◽

2017 ◽

Vol 43 (5-6) ◽

pp. 266-271 ◽

Cited By ~ 9

Author(s):

Bhaskar Roy ◽

Louise D. McCullough ◽

Rajat Dhar ◽

James Grady ◽

Yu-Bo Wang ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Adverse Effects ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Response To Therapy ◽

Discharge Disposition ◽

Induced Hypertension ◽

Baseline Characteristics ◽

The Impact

Background: The main reason for morbidity after aneurysmal subarachnoid hemorrhage (aSAH) is delayed cerebral ischemia (DCI). The mainstay of medical therapy for treating DCI is induced hypertension with vasopressors to restore cerebral perfusion. Both phenylephrine (PE) and norepinephrine (NE) are commonly used for induced hypertension, but the impact of the initial choice of vasopressor on the efficacy, adverse effects, or outcome after hemodynamic therapy for DCI is unknown. Methods: Sixty-three patients with aSAH between January 2012 and October 2014, who developed DCI (defined as new focal deficit or decline in Glasgow Coma Score) and in which PE (n = 45) or NE (n = 18) treatment was initiated were evaluated in this retrospective study. Baseline characteristics, adverse effects, the need to change or add vasopressors, the response to therapy, the need for endovascular therapy, new infarct development, discharge disposition, and 3 months modified Rankin score were all compared between pressor groups. Results: Baseline characteristics (e.g., Hunt Hess and Fisher grades) were similar. There were no differences in the overall rate of complications including arrhythmia, pulmonary edema, or kidney injury. However, those initiated on PE were more likely to be changed to an alternate vasopressor (64 vs. 33%, p = 0.016), mostly for bradycardia or failure to reach therapeutic targets. Patients initially treated with PE were less likely to respond neurologically (71 vs. 94%, p = 0.01) or to be discharged to home or acute rehabilitation facilities (73 vs. 94%, p = 0.02) and were more likely to have a delayed infarct on imaging (62 vs. 33%, p = 0.04). Conclusions: Our study suggests that patients with DCI after aSAH initiated on PE are more likely to require treatment change to another vasopressor and are at greater risk for poor clinical outcomes compared to patients started on NE. Larger comparative studies are warranted.

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Apolipoprotein E genotype and outcome after aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/2008.11.jns081266 ◽

2009 ◽

Vol 110 (5) ◽

pp. 989-995 ◽

Cited By ~ 21

Author(s):

Seppo Juvela ◽

Jari Siironen ◽

Jaakko Lappalainen

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Cerebral Infarction ◽

Apolipoprotein E ◽

Clinical Condition ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Univariate Analysis ◽

Delayed Cerebral Ischemia ◽

Intracerebral Hematoma ◽

Poor Outcome

Object After aneurysmal subarachnoid hemorrhage (SAH), conflicting results concerning an association between the APOE genotype and impaired outcome have been reported. The authors tested prospectively whether APOE ε2 or ε4 allele–containing genotypes (ε2+ and ε4+) affect outcome after SAH. Methods Previous disease histories and clinical and radiological variables were recorded for 105 patients who were admitted within 48 hours after SAH. Fifteen patients (14%) had the ε2+ genotype and 31 (17%) had ε4+ genotypes. Factors predicting poor outcome according to the Glasgow Outcome Scale and cerebral infarction visible on CT scans obtained at 3 months after SAH were tested with multiple logistic regression analyses. Results Apolipoprotein E ε2 or ε4–containing genotypes were not associated with outcome, occurrence of cerebral infarction, or with any of their predictors, either in univariate or multivariate analysis. Poor outcome was predicted independently by the occurrence of intraventricular bleeding and intracerebral hematoma as well as by elevated levels of both plasma glucose and D-dimer, and delayed cerebral ischemia (p < 0.05 for each factor), and in univariate analysis only by clinical condition on admission and patient age. Cerebral infarction was predicted independently according to clinical condition on admission (p < 0.05), amount of subarachnoid blood (p < 0.01), duration of intraoperative parent artery clipping (p < 0.01), and body mass index (p < 0.05). In the univariate analysis only cerebral infarction was also predicted by patient age, intracerebral hematoma, and delayed cerebral ischemia. Conclusions Severity of bleeding for the most part predicts outcome after SAH; APOE polymorphisms seem to have no prognostic value for outcome after SAH. This result was in accordance with the findings from the largest ischemic stroke studies.

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Vasospasm on transcranial Doppler is predictive of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis

Journal of Neurosurgery ◽

10.3171/2015.4.jns15428 ◽

2016 ◽

Vol 124 (5) ◽

pp. 1257-1264 ◽

Cited By ~ 49

Author(s):

Gyanendra Kumar ◽

Reza Bavarsad Shahripour ◽

Mark R. Harrigan

Keyword(s):

Systematic Review ◽

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Transcranial Doppler ◽

Predictive Value ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Meta Analysis ◽

Delayed Cerebral Ischemia ◽

Patient Centered ◽

The Impact

OBJECT The impact of transcranial Doppler (TCD) ultrasonography evidence of vasospasm on patient-centered clinical outcomes following aneurysmal subarachnoid hemorrhage (aSAH) is unknown. Vasospasm is known to lead to delayed cerebral ischemia (DCI) and poor outcomes. This systematic review and meta-analysis evaluates the predictive value of vasospasm on DCI, as diagnosed on TCD. METHODS MEDLINE, Scopus, the Cochrane trial register, and clinicaltrials.gov were searched through September 2014 using key words and the terms “subarachnoid hemorrhage,” “aneurysm,” “aneurysmal,” “cerebral vasospasm,” “vasospasm,” “transcranial Doppler,” and “TCD.” Sensitivities, specificities, and positive and negative predictive values were pooled by a DerSimonian and Laird random-effects model. RESULTS Seventeen studies (n = 2870 patients) met inclusion criteria. The amount of variance attributable to heterogeneity was significant (I2 > 50%) for all syntheses. No studies reported the impact of TCD evidence of vasospasm on functional outcome or mortality. TCD evidence of vasospasm was found to be highly predictive of DCI. Pooled estimates for TCD diagnosis of vasospasm (for DCI) were sensitivity 90% (95% confidence interval [CI] 77%–96%), specificity 71% (95% CI 51%–84%), positive predictive value 57% (95% CI 38%–71%), and negative predictive value 92% (95% CI 83%–96%). CONCLUSIONS TCD evidence of vasospasm is predictive of DCI with high accuracy. Although high sensitivity and negative predictive value make TCD an ideal monitoring device, it is not a mandated standard of care in aSAH due to the paucity of evidence on clinically relevant outcomes, despite recommendation by national guidelines. High-quality randomized trials evaluating the impact of TCD monitoring on patient-centered and physician-relevant outcomes are needed.

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Reactive Thrombocytosis in Non-aneurysmal Subarachnoid Hemorrhage

Journal of Neurological Surgery Part A Central European Neurosurgery ◽

10.1055/s-0040-1709167 ◽

2020 ◽

Vol 81 (05) ◽

pp. 412-417

Author(s):

Daniel Dubinski ◽

Sae-Yeon Won ◽

Bedjan Behmanesh ◽

Nina Brawanski ◽

Volker Seifert ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Vasospasm ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

World Federation ◽

Reactive Thrombocytosis ◽

Vp Shunt ◽

Fisher Grade ◽

The Impact

Abstract Background The role of reactive thrombocytosis in non-aneurysmal subarachnoid hemorrhage (NA-SAH) is largely unexplored to date. Therefore, the impact of a quantitative thrombocyte dynamic in patients with NA-SAH and its clinical relevance were analyzed in the present study. Methods In this retrospective analysis, 113 patients with nontraumatic and NA-SAH treated between 2003 and 2015 at our institution were included. World Federation of Neurosurgical Societies admission status, cerebral vasospasm, delayed infarction, hydrocephalus, need for ventriculoperitoneal (VP) shunt, and Fisher grade were analyzed for their association with reactive thrombocytosis. Results Reactive thrombocytosis was not associated with hydrocephalus (p ≥ 0.05), need for VP shunt implantation (p ≥ 0.05), cerebral vasospasm (p ≥ 0.05), or delayed cerebral ischemia (p ≥ 0.05). Conclusion Our study is the first to investigate the role of thrombocyte dynamics, reactive thrombocytosis, and the clinical course of NA-SAH patients. Our analysis showed no significant impact of thrombocyte count on NA-SAH sequelae.

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The Impact of Nimodipine Administration through Feeding Tube on Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/jpps30960 ◽

2020 ◽

Vol 23 ◽

pp. 100-108

Author(s):

Fadumo Ahmed Isse ◽

Yasmeen El Hajj Abdallah ◽

Sherif Hanafy Mahmoud

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Enteral Feeding ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Retrospective Chart Review ◽

Feeding Tube ◽

P Value ◽

Feeding Tubes ◽

The Impact

PURPOSE: Delayed cerebral ischemia (DCI) and vasospasm are the main challenges contributing to unfavorable outcomes following aneurysmal subarachnoid hemorrhage. Nimodipine has been shown to decrease the incidence of delayed cerebral ischemia and improve outcomes. In patients who are unable to swallow, nimodipine tablets are crushed and administered through enteral feeding tubes. However, it is not clear whether this may result in reduced clinical effectiveness. The aims of the study were to investigate the impact of nimodipine administration through enteral feeding tubes, in the first 7 days and over the 21-days period on patient outcomes. METHODS: A retrospective chart review of subarachnoid hemorrhage patients admitted at the University of Alberta Hospital, Edmonton, Alberta, Canada was carried out. Logistic regression modelling was utilized to identify predictors of vasospasm and delayed cerebral ischemia. Main outcome measures were angiographic evidence of moderate to severe vasospasm, development of delayed cerebral ischemia and hospital mortality. RESULTS: 85 patients were included. Following adjustment for disease severity, nimodipine administration technique was associated with vasospasm in the first 7 days of patient admission where patients receiving nimodipine via enteral feeding tubes had increased odds of vasospasm compared to those administered it as whole tablets (OR 8.9, 95% CI 1.1-73.1, p value 0.042). When analyzed over the 21-day period, nimodipine administration by feeding tube was associated with increased odds of DCI compared to whole tablets (OR 38.1, 95% CI 1.4-1067.9, p value 0.032). CONCLUSIONS: Our findings suggest that nimodipine administration via enteral feeding tubes may be associated with vasospasm and DCI in subarachnoid hemorrhage patients secondary to reduced exposure. Prospective studies are needed to confirm such association and alternate methods of administration should be explored to ensure patients are getting the benefits of nimodipine.

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The impact of temporary clipping during aneurysm surgery on the incidence of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/2017.3.jns162505 ◽

2018 ◽

Vol 129 (1) ◽

pp. 84-90 ◽

Cited By ~ 6

Author(s):

Vesna Malinova ◽

Bawarjan Schatlo ◽

Martin Voit ◽

Patricia Suntheim ◽

Veit Rohde ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Aneurysm Surgery ◽

Flow Acceleration ◽

Ruptured Intracranial Aneurysm ◽

Clinical Series ◽

The Impact ◽

Temporary Clipping

OBJECTIVEClipping of a ruptured intracranial aneurysm requires some degree of vessel manipulation, which in turn is believed to contribute to vasoconstriction. One of the techniques used during surgery is temporary clipping of the parent vessel. Temporary clipping may either be mandatory in cases of premature rupture (rescue) or represent a precautionary or facilitating surgical step (elective). The aim of this study was to study the association between temporary clipping during aneurysm surgery and the incidence of vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (aSAH) in a large clinical series.METHODSSeven hundred seventy-eight patients who underwent surgical aneurysm treatment after aSAH were retrospectively included in the study. In addition to surgical parameters, the authors recorded transcranial Doppler (TCD) sonography–documented vasospasm (TCD-vasospasm, blood flow acceleration > 120 cm/sec), delayed ischemic neurological deficits (DINDs), and delayed cerebral infarction (DCI). Multivariate binary logistic regression analysis was applied to assess the association between temporary clipping, vasospasm, DIND, and DCI.RESULTSTemporary clipping was performed in 338 (43.4%) of 778 patients during aneurysm surgery. TCD sonographic flow acceleration developed in 370 (47.6%), DINDs in 123 (15.8%), and DCI in 97 (12.5%). Patients with temporary clipping showed no significant increase in the incidence of TCD-vasospasm compared with patients without temporary clipping (49% vs 48%, respectively; p = 0.60). DINDs developed in 12% of patients with temporary clipping and 18% of those without temporary clipping (p = 0.01). DCI occurred in 9% of patients with temporary clipping and 15% of those without temporary clipping (p = 0.02). The need for rescue temporary clipping was a predictor for DCI; 19.5% of patients in the rescue temporary clipping group but only 11.3% in the elective temporary clipping group had infarcts (p = 0.02). Elective temporary clipping was not associated with TCD-vasospasm (p = 0.31), DIND (p = 0.18), or DCI (p = 0.06).CONCLUSIONSTemporary clipping did not contribute to a higher rate of TCD-vasospasm, DIND, or DCI in comparison with rates in patients without temporary clipping. In contrast, there was an association between temporary clipping and a lower incidence of DINDs and DCI. There is no reason to be hesitant in using elective temporary clipping if deemed appropriate.

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Microthrombosis after Aneurysmal Subarachnoid Hemorrhage: An Additional Explanation for Delayed Cerebral Ischemia

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2008.74 ◽

2008 ◽

Vol 28 (11) ◽

pp. 1761-1770 ◽

Cited By ~ 176

Author(s):

Mervyn DI Vergouwen ◽

Marinus Vermeulen ◽

Bert A Coert ◽

Erik SG Stroes ◽

Yvo BWEM Roos

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Time Window ◽

Clinical Symptoms ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Coagulation Cascade ◽

Future Research ◽

Increased Risk ◽

Depth Analysis

Patients with aneurysmal subarachnoid hemorrhage (SAH) who experience delayed cerebral ischemia (DCI) have an increased risk of poor outcome. Delayed cerebral ischemia is considered to be caused by vasospasm. However, not all patients with DCI have vasospasm. Inversely, not all patients with vasospasm develop clinical symptoms and signs of DCI. In the past, treatments aiming at vasospasm were not successful in preventing ischemia. The purpose of this review is to give an overview of clinical data showing that DCI cannot always be attributed to vasospasm, and to present an in-depth analysis of clinical and autopsy studies on the role of microthrombosis in the pathogenesis of DCI. Clinical studies show that DCI is associated with an activation of the coagulation cascade within a few days after SAH, preceding the time window during which vasospasm occurs. Furthermore, impaired fibrinolytic activity, and inflammatory and endothelium-related processes, lead to the formation of microthrombi, which ultimately result in DCI. The presence of microthrombi is confirmed by autopsy studies. Insight in the pathophysiology of DCI is crucial for the development of effective therapies against this complication. Because multiple pathways are involved, future research should focus on drugs with pleiotropic effects.

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