Article

Early Identification of Individuals at High Risk for Cerebral Infarction after Aneurysmal Subarachnoid Hemorrhage: The BEHAVIOR Score

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Abstract

Cerebral infarction (CI) is a crucial complication of aneurysmal subarachnoid hemorrhage (SAH) associated with poor clinical outcome. We aimed at developing an early risk score for CI based on clinical characteristics available at the onset of SAH. Out of a database containing 632 consecutive patients with SAH admitted to our institution from January 2005 to December 2012, computed tomography (CT) scans up to day 42 after ictus were evaluated for CIs. Different parameters from admission up to aneurysm treatment were collected with subsequent construction of a risk score. Seven clinical characteristics were independently associated with CI and included in the Risk score (BEHAVIOR Score, 0 to 11 points): Blood on CT scan according to Fisher grade ⩾3 (1 point), Elderly patients (age ⩾55 years, 1 point), Hunt&Hess grade ⩾4 (1 point), Acute hydrocephalus requiring external liquor drainage (1 point), Vasospasm on initial angiogram (3 points), Intracranial pressure elevation >20 mm Hg (3 points), and treatment of multiple aneurysms ('Overtreatment', 1 point). The BEHAVIOR score showed high diagnostic accuracy with respect to the absolute risk for CI (area under curve=0.806, P<0.0001) and prediction of poor clinical outcome at discharge (P<0.0001) and after 6 months (P=0.0002). Further validation in other SAH cohorts is recommended.Journal of Cerebral Blood Flow & Metabolism advance online publication, 29 April 2015; doi:10.1038/jcbfm.2015.81.

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... The diagnosis was usually made by comparing the DSA on admission with the DSA at the time of suspected cerebral vasospasm. Early angiographic vasospasm on admission was not taken into account [11][12][13]. To our knowledge, reference values for intracranial arteries on DSA are still not systematically defined. ...
... The onset of early angiographic vasospasm was evaluated according to Jabbarli et al. [13]. Angiograms were analyzed up to 72 h after SAH for pre-existing early angiographic vasospasm and scored with the BEHAVIOR score according to Jabbarli et al. [13]. ...
... The onset of early angiographic vasospasm was evaluated according to Jabbarli et al. [13]. Angiograms were analyzed up to 72 h after SAH for pre-existing early angiographic vasospasm and scored with the BEHAVIOR score according to Jabbarli et al. [13]. Early angiographic vasospasm was evaluated on diagnostic angiograms before intracranial aneurysm treatment without spasmolytic therapy. ...
Article
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Background: During the last decade, cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) was a current research focus without a standardized classification in digital subtraction angiography (DSA). This study was performed to investigate a device-independent visual cerebral vasospasm classification for endovascular treatment. Methods: The analyses are DSA based rather than multimodal. Ten defined points of intracranial arteries were measured in 45 patients suffering from cerebral vasospasm after SAH at three time points (hospitalization, before spasmolysis, control after six months). Mathematical clustering of vessel diameters was performed to generate four objective grades for comparison. Six interventional neuroradiologists in two groups scored 237 DSAs after a new visual classification (grade 0-3) developed on a segmental pattern of vessel contraction. For the second group, a threshold-based criterion was amended. Results: The raters had a reproducibility of 68.4% in the first group and 75.2% in the second group. The complementary threshold-based criterion increased the reproducibility by about 6.8%, while the rating deviated more from the mathematical clustering in all grades. Conclusions: The proposed visual classification scheme of cerebral vasospasm is suitable as a standard grading procedure for endovascular treatment. There is no advantage of a threshold-based criterion that compensates for the effort involved. Automated vessel analysis is superior to compare inter-group results in research settings.
... Therefore, the severity of symptomatic vasospasm was judged upon the need for angioplasty and/or repetitive endovascular treatments. The detailed description of clinical management of SAH patients at our institution has already been reported previously [9][10][11] . ...
... All previous publications uniquely point to the high risk of poor functional outcome in patients developing EAVS after aneurysm rupture [6,7,9] . Furthermore, strong associations between EAVS with early [9] and delayed [6,11] cerebral infarctions could also be shown. In particular, EAVS was included to a risk score (BEHAVIOR score) for prediction of cerebral infarction after SAH in our recent publication [11] . ...
... Furthermore, strong associations between EAVS with early [9] and delayed [6,11] cerebral infarctions could also be shown. In particular, EAVS was included to a risk score (BEHAVIOR score) for prediction of cerebral infarction after SAH in our recent publication [11] . Our present extended analysis shows the dramatic impact of EAVS on the occurrence of DCI in SAH patients. ...
Article
Background: Cerebral vasospasm usually develops several days after subarachnoid hemorrhage (SAH) and is generally acknowledged as a strong outcome predictor. In contrast, much less is known about the nature and eventual consequences of early angiographic vasospasm (EAVS) seen on admission digital subtraction angiography (DSA). Therefore, we aimed at identifying the risk factors and clinical impact of EAVS after SAH. Methods: Five hundred and thirty-one SAH patients with admission DSA performed within 72 h after the bleeding event were selected from a comprehensive database containing all consecutive SAH patients treated at our institution between January 2005 and December 2012. Predictors of EAVS, as well as associations between EAVS and delayed vasospasm-related complications, and unfavorable outcome (defined as modified Rankin scale >3) were evaluated in univariate and multivariate analyses. Results: EAVS was seen on 60 DSAs (11.3%) and was independently correlated with delayed symptomatic vasospasm requiring intra-arterial spasmolysis (OR 5.24, p < 0.0001), angioplasty (OR 2.56, p = 0.015) and repetitive endovascular treatment (OR 4.71, p < 0.0001). EAVS also increased the risk for multiple versus single territorial infarction on the follow-up CT scan(s) (OR 2.04, p = 0.047) and independently predicted unfavorable outcome (OR 2.93, p = 0.008). The presence of radiographic signs suspicious for fibromuscular dysplasia were independently associated with the occurrence of EAVS (OR 2.98, p = 0.026) and the need for repetitive endovascular vasospasm treatment (OR 3.95, p = 0.019). Conclusions: In view of the strong correlation with delayed symptomatic vasospasm and its ischemic complications, EAVS can be considered an alerting signal for severe symptomatic vasospasm. Therefore, more attention should be paid to the presence of EAVS on admission DSA.
... All patients underwent at least 1 posttreatment CT scan, and additional CT scans were obtained upon clinical indications. 13 Transcranial Doppler (TCD) ultrasonography was performed daily during the first 3 weeks after SAH, in which absolute mean flow velocities > 160 cm/sec were deemed suspicious for clinically relevant vasospasm. The different aspects of SAH management at our institution have already been elaborated on in our previous publications. ...
... The different aspects of SAH management at our institution have already been elaborated on in our previous publications. [11][12][13][14] ...
... Considerable morbidity and mortality after SAH is generally acknowledged to be multifactorial in nature. 13 Therefore, SAH patients with A1SA on admission DSA, and especially those with disturbed consciousness, may be considered for intensive surveillance of the cerebral perfusion in the ACA territory by means of additional diagnostic tools such as perfusion CT imaging (at predefined time intervals), continuous electrophysiological monitoring, microdialysis, or near-infrared spectroscopy. ...
Article
OBJECTIVE An asymmetry of the A 1 segments (A1SA) of the anterior cerebral arteries (ACAs) is an assumed risk factor for the development of anterior communicating artery aneurysms (ACoAAs). It is unknown whether A1SA is also clinically relevant after aneurysm rupture. The authors of this study investigated the impact of A1SA on the clinical course and outcome of patients with aneurysmal subarachnoid hemorrhage (SAH). METHODS The authors retrospectively analyzed data on consecutive SAH patients treated at their institution between January 2005 and December 2012. The occurrence and severity of cerebral infarctions in the ACA territories were evaluated on follow-up CT scans up to 6 weeks after SAH. Moreover, the risk for an unfavorable outcome (defined as > 3 points on the modified Rankin Scale) at 6 months after SAH was assessed. RESULTS A total of 594 patients were included in the final analysis. An A1SA was identified on digital subtraction angiography studies from 127 patients (21.4%) and was strongly associated with ACoAA (p < 0.0001, OR 13.7). An A1SA independently correlated with the occurrence of ACA infarction in patients with ACoAA (p = 0.047) and in those without an ACoAA (p = 0.015). Among patients undergoing ACoAA coiling, A1SA was independently associated with the severity of ACA infarction (p = 0.023) and unfavorable functional outcome (p = 0.045, OR = 2.4). CONCLUSIONS An A1SA is a common anatomical variation in SAH patients and is strongly associated with ACoAA. Moreover, the presence of A1SA independently increases the likelihood of ACA infarction. In SAH patients undergoing ACoAA coiling, A1SA carries the risk for severe ACA infarction and thus an unfavorable outcome. Clinical trial registration no.: DRKS00005486 ( http://www.drks.de/ )
... [4] Many other prediction models have been developed and published, and some of them use different parameters to calculate various outcomes that are associated with DCI and vasospasm. [1,2,7] Here, we present the SAH DCI app, which was developed to facilitate comparison between the various grading scales and to aid physicians in the use of prediction models. It incorporates automated calculation of a maximum of seven SAH grading scales, namely, the WFNS SAH grade, the Hunt and Hess grade, the original and modified Fisher grade, the early prediction scale by De Rooij et al., the BEHAVIOR score, and the VASOGRADE score. ...
... It incorporates automated calculation of a maximum of seven SAH grading scales, namely, the WFNS SAH grade, the Hunt and Hess grade, the original and modified Fisher grade, the early prediction scale by De Rooij et al., the BEHAVIOR score, and the VASOGRADE score. [1][2][3][4]6,7,9] The WFNS SAH grade and the Hunt and Hess grade are general outcome predictors, and the other classification systems are specific predictors for DCI. ...
... The basic module asks 4 questions to calculate 3 grading scales (WFNS SAH Grade, [9] Modified Fisher, [4] and VASOGRADE [1] ) An example is illustrated in Figure 1. The advanced module asks 10 questions to calculate 7 grading scales (the WFNS SAH grade, [9] the Hunt and Hess grade, [6] original and modified Fisher grade, [3,4] early prediction scale by De Rooij et al., [2] the BEHAVIOR score, [7] and the VASOGRADE score [1] ). An example is illustrated in Figure 2. ...
... 1 Factors contributing to DCI have been extensively investigated and include vasospasm, higher age, elevation of intracranial pressure, initial clinical condition, radiographic severity of SAH, and acute hydrocephalus. 2 Current strategies on DCI prevention consist of early recognition of vasospasm and timely application of conservative (euvolemia, nimodpine) and invasive (endovascular spasmolysis) treatment modalities. 3 Along with the above-mentioned risk factors, the influence of platelet activity on DCI has also been analyzed. Strong associations between vasospasm/DCI occurrence and activation of platelets and thromboxane A2 (a platelet-related factor) in SAH patients were reported. ...
... 22 Risk factors include clinical condition at admission, occurrence of symptomatic vasospasm, and initial radiographic severity of SAH. 2 Recently, other factors like neuroinflammation and cortical spreading depolarization have been intensively disputed as potential DCI confounders. 23 Finally, microthrombosis has also been described to play an essential role in DCI development. ...
Article
BACKGROUND: Delayed cerebral ischemia (DCI) has a strong impact on outcome of patients with aneurysmal subarachnoid hemorrhage (SAH). Positive effect of antiplatelet therapy on DCI rates has been supposed upon smaller SAH series. OBJECTIVE: To analyze the benefit/risk profile of antiplatelet use in SAH patients. METHODS: This retrospective case-control study was based on institutional observational cohort with 994 SAH patients treated between January 2003 and June 2016. The individuals with postcoiling antiplatelet therapy (aspirin with/without clopidogrel) were compared to a control group without antiplatelet therapy. Occurrence of DCI, major/minor bleeding events in the follow-up computed tomography scans, and favorable outcome at 6 mo after SAH (modified Rankin scale < 3) were compared in both groups. RESULTS: Of 580 patients in the final analysis, 329 patients received post-treatment antiplatelet medication. There were no significant differences between the compared groups with regard to basic outcome confounders. Aspirin use was independently associated with reduced DCI risk (P < .001, adjusted odds ratio = 0.41, 95% confidence interval 0.24-0.65) and favorable outcome (P = .02, adjusted odds ratio = 1.78, 95% confidence interval 1.06-2.98). Regarding bleeding complications, aspirin was associated only with minor bleeding events (P = .02 vs P = .51 for major bleeding events). CONCLUSION: Regular administration of aspirin might have a positive impact on DCI risk and outcome of SAH patients, without increasing the risk for clinically relevant bleeding events. In our SAH cohort, dual antiplatelet therapy showed no additional benefit on DCI risk, but increased the likelihood of major bleeding events.
... A wide variety of clinical signs and risk factors for developing both CVS and DCI have been described, including smoking 16 , hypertension 16,17 , hyperglycemia 16,17 , old age 18,19 , and level of consciousness 20,21 , as well as image-based scoring systems such as modified Fisher score (MFS) 22,23 . However, much of the literature is difficult to interpret as outcomes are often poorly defined 24 . ...
... Individual chart-review supplemented clinical factors not expected to be captured in the CDW retrieval, including level of consciousness, and World Federation of Neurosurgeons grade. The specific model features extracted were: hypertension 16,17 , smoking status 16 , hyperglycemia 16 , diabetes mellitus 16 , increased intracranial pressure 19 , leukocytosis 34 , level of consciousness 20,21 , weight 17 , World Federation of Neurosur-geons grade 35,36 , and blood transfusion 37 , MFS 22,23 , aneurysm treatment (surgical clipping or endovascular coil) 38 , presence of perfusion mismatch on CTP 13,14,39 , TCD vessel elevation > 140cm/sec 11 , CVS on CTA 14,15 , CVS on DSA 14,15 , aneurysm location, number of aneurysms and aneurysm size 37 . Inclusion criteria are patients 18 years of age or older with documented aSAH at admission based on the results of head CTA or DSA. ...
Article
The goal of this study was to investigate the application of machine learning models capable of capturing multiplica tive and temporal clinical risk factors for outcome prediction inpatients with aneurysmal subarachnoid hemorrhage (aSAH). We examined a cohort of 575 aSAH patients from Emory Healthcare, identified via digital subtraction angiog- raphy. The outcome measure was the modified Ranking Scale (mRS) after 90 days. Predictions were performed with longitudinal clinical and imaging risk factors as inputs into a regularized Logistic Regression, a feedforward Neural Network and a multivariate time-series prediction model known as the long short-term memory (LSTM) architecture. Through extraction of higher-order risk factors, the LSTM model achieved an AUC of 0.89 eight days into hospitaliza tion, outperforming other techniques. Our preliminary findings indicate the proposed model has the potential to aid treatment decisions and effective imaging resource utilization in high-risk patients by providing actionable predictions prior to the development of neurological deterioration.
... Alongside with initial severity of SAH and aneurysm rebleeding prior to treatment [5,19], certain secondary complications also contribute to morbidity and mortality of SAH [18]. Among them, delayed cerebral ischemia (DCI) is a major risk factor for SAH patients with successful aneurysm treatment and uncomplicated initial course [1]. ...
... However, poor initial clinical condition of the majority of DCI candidates, as well as clinical manifestation usually occurring at the time of irreversible cerebral damages, necessitated development of novel diagnostic approaches [31]. In particular, there are a large number of studies focusing on predictors of vasospasm and DCI [6,8,12,18,21]. But the amount of intracranial bleeding is the only consistently demonstrated risk factor for vasospasm [16]. Transcranial Doppler (TCD) ultrasonography is the most common non-invasive bedside tool for identification of vasospasm, but is characterized with a moderate specificity and predictive value [22]. ...
Article
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Delayed cerebral ischemia (DCI) is a severe complication of subarachnoid hemorrhage (SAH). Clinical and radiographic features of SAH may be helpful in identification of individuals prone to DCI. The aim of this systematic review was to analyze the present evidence on predictive value of blood and cerebrospinal fluid (CSF) biomarkers of DCI after SAH. We systematically searched in PubMed, Scopus, Web of Science, and Cochrane Library databases for publications before July 15, 2018, reporting correlations between blood/CSF biomarkers and occurrence of DCI and/or vasospasm in SAH patients. Included studies underwent quality assessment according to QUIPS and STARD guidelines. Level of evidence (I–IV) for each of tested biomarkers was assessed according to GRADE guidelines. Of 2181 unique records identified in four databases, 270 original articles and 5 meta-analyses were included to this review. Of 257 blood and CSF parameters analyzed in 16.914 SAH patients, there was no biomarker with positive association with DCI/vasospasm showing level I evidence. Twenty-one biomarkers achieved level II evidence and could be confirmed as predictive biomarkers. In this review, six single nucleotide polymorphisms (for EET metabolic pathways, COMT, HMGB1, ACE, PAI-1 promoter, and Hp genes) and 15 non-genetic biomarkers (pNF-H, ADAMTS13, NPY, Copeptin, HMGB1, GFAP, periostin, Tau, BNP, NT pro-BNP, hs-TnT, PA-TEGMA, MPV:PLT, NLR, and PLR) were selected as predictive DCI biomarkers. We propose that a panel analysis of the selected genetic and protein biomarker candidates would be needed for further validation in a large SAH cohort.
... A coherent multidisciplinary approach will help determine whether connectome-based analysis of the epileptogenic network can be used to improve surgical procedures, including minimally invasive neuroablative methods, and to refine current MRI-based predictors of surgical outcome. Ischaemia is a common consequence of subarachnoid haemorrhage (SAH), affecting approximately 20-40% of patients (Jabbarli et al., 2015). Some of these patients fall into the category of acute cerebral ischaemia (ACI), defined as signs of ischaemia on head imaging within 3 days of the bleed. ...
... Natural history estimates an overall mortality rate of about 50% [1,14]. The most important prognostic factors are initial neurological grade at admission, patient characteristics (smoking, hypertension), SAH grade (H/ H, Fisher score/volume of blood on initial CT), and in particular cerebral infarction [2,7,15,24,31]. Studies on optimization SAH treatment continue to be subject of clinical and experimental research. Changes in microcirculation and increased expression of various biomarkers in association of inflammatory processes are possible reasons for the etiology of CVS and cerebral infarction (CI). ...
Article
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The basilar artery (BA), as a reference vessel for laboratory investigations of cerebral vasospasm (CVS) in many experimental models, warrants a sufficient blood supply despite hemodynamic changes during CVS. In a prospective evaluation study, we analyzed patients who were admitted to our department with subarachnoid hemorrhage (SAH) for the occurrence and sequelae of CVS. Specifically, we sought to identify patients with CVS of the BA. As per institutional protocol, all patients with CVS detected in the posterior circulation had magnetic resonance imaging (MRI) examinations instead of CTA. Between January and December 2016, 74 patients were treated for spontaneous SAH. CVS occurred in 45 (61%) patients, and 31 (42%) patients developed associated cerebral infarctions (CI). CVS was significantly associated with CI (p < 0.0001; OR 44). In 18 (24.3%) patients, CVS significantly affected the basilar artery. Poor admission clinical state, younger age, and treatment modalities were significantly associated with BACVS. BACVS was more often detected in patients with severe CVS (p < 0.046; OR 4.4). Patients with BACVS developed cerebral infarction in a frequency comparable to other patients with CVS (61% vs. 70%, p = 0.7), but none of these infarctions occurred in the brain stem or pons even though vessel diameter was dramatically reduced according to CT- and/or MR-angiography. BACVS does not appear to be followed by cerebral infarction in the BA territory, presumably due to a vascular privilege of this vessel and its perforating branches. In contrast, brain ischemia can frequently be observed in the territories of other major arteries affected by CVS.
... 1, 2, 6-10, 12-14, 17-19, 23, 25, 27-29, 32, 41, 43, 45, 46, 49-51, 53, 55, 58-60, 64, 65, 68, 79, 85, 87-89, 95-102, 104, 106-109, 111, 117, 119, 121, 122, 125-127, 131, 135, 138, 139, 143, 144, 147, 148, 150, 154, 155, 157-159, 162, 163, 166, 169, 170, 173-176 Studies based on North American and European cohorts 2, 6, 9, 16-22, 34, 35, 37, 41, 45-47, 50-53, 55, 58-64, 71-73, 110, 111, 119-124, 129-131, 133-135, 137-143, 146, 148, 150, 152, 154, 155, 160, 163-175 Studies based on Asian and African cohorts Studies using autopsies at least partially (performed between 1951 -1997) 34,47,130,134,152,164,168,171 (D)SA-only studies timely matching to the previous study subgroup (studies using autopsies at least partially) 11,16,35,42,52,71,90,124,129,132,133,165,167 Studies from North American and European cohorts performed during the last 15 years (2000 -2015) 51,59,60,64,121,122,138,143,155,158,163,166,169,170,173,175 Studies based on pediatric populations 67,128,137,140,142,146 Studies reporting the prevalence of comorbidities in their populations 2, 6, 9, 10, 12-14, 25, 27, 29, 34, 41, 42, 45, 47, 60, 68, 74, 77, 79, 80, 87, 89, 92, 95, 100, 102, 104, 119, 123, 130, 131, 133, 138, 143, 147, 150, 152, 155, 160, 162, 164, 166, 169, 170, 173, 175 Studies reporting the prevalence of alcohol consumers in their populations 9,10,25,29,42,80,131,138,143,147,152,169,173,175 Figure I: Meta-Analysis of association between the patients age and the presence of MIA ...
Article
Background and purpose: Multiple intracranial aneurysms (MIAs) are common findings of cerebral angiographies; however, MIA prevalence varies in different patient cohorts. We sought to elucidate risk factors influencing MIA prevalence and the clinical consequences. Methods: We systematically searched PubMed, Scopus, Embase, and Cochrane Library databases for publications before January 15, 2017, reporting MIA prevalence and risk factors. We used random-effects meta-analysis and multivariate regression analysis to assess the impacts of individual, study, and population characteristics. Results: We included 174 studies reporting on MIA (mean overall prevalence, 20.1%; range, 2%-44.9%) in 134 study populations with 86 989 intracranial aneurysm (IA) patients enrolled between 1950 and 2015. Studies from Europe and North America (P<0.001) and more recent enrolment years (P=0.046) were independently associated with higher MIA prevalence. In meta-analysis, MIA correlated with female sex (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.4-1.8), higher patient age (>40 years; OR, 1.6; 95% CI, 1.14-2.25), arterial hypertension (OR, 1.51; 95% CI, 1.17-1.94), smoking (OR, 1.89; 95% CI, 1.37-2.6) and familial IA (OR, 2.02; 95% CI, 1.47-2.77), and formation of de novo (OR, 3.92; 95% CI, 1.95-7.87) and growth of initial IA (OR, 3.47; 95% CI, 1.87-6.45). Risk of subarachnoid hemorrhage in MIA patients was higher only in longitudinal studies from Japan and Korea (OR, 2.08; 95% CI, 1.46-2.96). Conclusions: Female sex, higher age, arterial hypertension, smoking, and familial IA are major risk factors for MIA. In addition, MIA patients are at risk for enhanced IA formation. Further studies are needed to evaluate rupture risk and the role of ethnicity, especially in the context of increased MIA identification with improved neurovascular imaging.
... [2][3][4][5] Established clinical and radiographic predictors for vasospasm include patient age, Hunt and Hess (HH) grade, and modified Fisher (mFisher) grade. 6,7 However, the prediction of vasospasm with existing models remains imperfect, and it would be advantageous to further refine risk stratification of vasospasm before the spasm window. Current treatments for vasospasm, including hemodynamic augmentation, balloon angioplasty, and/or intra-arterial application of vasodilators, are not without systemic consequences and/or periprocedural risks. ...
Article
Introduction Prediction of vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) remains imperfect and currently relies on clinical and radiographic characteristics. Whether early hemodynamic changes may refine risk stratification for delayed vasospasm (DV) after aSAH was analyzed. Methods Patients with aSAH (n=53) and a control of unruptured intracranial aneurysms (UIA) (n=12) with initial color-coding angiography at admission were included in this study (n=65). Clinical and radiological data were collected and uni- and multivariate analysis were used to correlate the occurrence of DV (manifesting clinically or detected with transcranial Doppler or angiography) with hemodynamic features of the initial angiography including Tmax and mean transit times (MTT). Results In the aSAH patient cohort, 37 of 53 aSAH patients (70%) developed DV. After controlling for the effects of age, HH grade and mFisher grade, patients with DV had a shorter mean Tmax of the anterior cerebral artery A2 segment (p=0.036) and the middle cerebral artery (MCA) M1 (p=0.045) and M3 (p=0.013) segments. Mean MTTs between internal carotid artery (ICA) to MCA M3 segment (p=0.026) was also significantly shorter in patients with DV when compared to control. Conclusions Tmax and MTT on angiography within 48 hours of aneurysm rupture prior to treatment provides an early quantitative assessment in SAH patients and in this small study was predictive for the development of subsequent symptomatic DV. Early identification of aSAH patients at greatest risk of DV may ameliorate clinical outcome through timely, selective implementation of aggressive prophylactic therapy to prevent the effects of DV.
... Those additional vessel manipulations incur an increased risk of arterial injury, which may eventually lead to cerebral ischemia. Aneurysmal SAH is known to be associated with a high risk of CI [9,27]. The risk of intraoperative rupture for UIAs has been reported to be fairly low [4,16]. ...
Article
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Cerebral infarction (CI) associated with clipping of unruptured intracranial aneurysms (UIAs) has not been completely studied. The role of individual and operative characteristics is not known, and the risk of silent CI has not been well described. To determine the incidence, risk factors, and clinical outcome of postoperative CI, we retrospectively analyzed 388 consecutive patients undergoing clipping of UIAs between January 2012 and December 2015. We reviewed the pre- and postoperative computed tomography (CT) images of each patient. Postoperative CI was defined as a new parenchymal hypodensity in the vascular territory of treated artery. Patient-specific, aneurysm-specific, and operative variables were analyzed as potential risk factors. Functional outcome at discharge was assessed with the modified Rankin Scale (mRS). Postoperative CI was found in 49 (12.6%) patients, 29 of whom manifested neurological deficits. The incidences of symptomatic stroke and silent CI were 7.5 and 5.2%, respectively. Multivariate analysis showed that larger aneurysm size and history of hypertension were significantly associated with CI. Disability (mRS > 2) rate was 42.9% among patients with CI, which was substantially higher than that among patients without (0.9%). In conclusion, the incidence of CI following clipping of UIAs was not low. Larger aneurysm size and history of hypertension were independent risk factors. Postoperative symptomatic stroke correlated with an extremely high risk of disability. Silent CI was seemingly nondisabling, but the possible cognitive consequence is pending.
... 'Behaviour' score was developed as an early risk score for CI based on the clinical parameters after aneurysmal SAH. This score, which showed the absolute risk for CI (area under curve = 0.806, P < 0.001) and prediction of poor clinical outcome at discharge (P < 0.0001); has high diagnostic accuracy in identifying patients at risk for developing CI after aneurysmal SAH (18). However, we were not able to apply this score to our daily neurosurgical practice. ...
Article
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Background: Morbidity and mortality is high among aneurysm rupture patients. Despite surviving the initial rupture, morbidity is high as they suffer from vasospasm and cerebral infarction (CI). Most prediction tools for CI after aneurysmal subarachnoid haemorrhage (SAH) are complex and are not routinely available in all neurosurgical centres. Current therapies for prevention of CI are still debatable and selective usage among high-risk patients is advised. These factors necessitate a simple prediction model for identifying patients in the high risk group to initiate early preventive treatment of CI. Methods: Patients with anterior circulation aneurysm rupture who underwent surgical clipping were included. Demographic data and factors related to CI were collected to determine significance and were used to develop VINODH score (VS). Results: Two hundred patients were included with a median age of 51 years old. Multivariate analysis proved only four predictors were significant (P < 0.01) for developing CI. These predictors were used for the development of VS which was named after the main author and the model's sensitivity was 79.0% and specificity was 83.0%. This highly predictive score (receiver operating characteristic [ROC]: 0.902) was internally validated. Conclusion: VS is a reliable tool for early identification of patients at risk of CI after aneurysmal SAH.
... 10 In a related paper, the authors reported a risk score for cerebral infarction (BEHAVIOR score) based on 7 independent predictors identified at multivariable analysis, including Fisher grade of SAH clot, patient age ≥ 55 years, Hunt and Hess grade, acute hydrocephalus requiring external CSF drainage, vasospasm on initial angiography, intracranial pressure greater than 20 mm Hg, and treatment of multiple aneurysms. 11 In addition, Kanamaru et al. recently published their post hoc analysis of predictors for cerebral infarction in 579 patients in the Prospective Registry of Subarachnoid Aneurysms Treatment (PRESAT). 13 The predictors were Fisher Grade 3 on admission, larger aneurysm dome size, ruptured posterior circulation aneurysms, premature aneurysm rupture during the clipping procedure, symptomatic vasospasm, and infection. ...
Article
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OBJECTIVE In this study the authors sought to investigate the sex differences in the risk of delayed cerebral ischemia (DCI), delayed cerebral infarction, and the role of hormonal status. METHODS Ten studies included in the SAHIT (SAH International Trialists) repository were analyzed using a fitting logistic regression model. Heterogeneity between the studies was tested using I ² statistics, and the results were pooled using a random-effects model. Multivariable analysis was adjusted for the effects of neurological status and fixed effect of study. An additional model was examined in which women and men were split into groups according to an age cut point of 55 years, as a surrogate to define hormonal status. RESULTS A pooled cohort of 6713 patients was analyzed. The risk of DCI was statistically significantly higher in women than in men (OR 1.29, 95% CI 1.12–1.48); no difference was found with respect to cerebral infarction (OR 1.17, 95% CI 0.98–1.40). No difference was found in the risk of DCI when comparing women ≤ 55 and > 55 years (OR 0.87, 95% CI 0.74–1.02; p = 0.08) or when comparing men ≤ 55 and > 55 years (p = 0.38). Independent predictors of DCI were World Federation of Neurosurgical Societies (WFNS) grade, Fisher grade, age, and sex. Independent predictors of infarction included WFNS grade, Fisher grade, and aneurysm size. CONCLUSIONS Female sex is associated with a higher risk of DCI. Sex differences may play a role in the pathogenesis of DCI but are not associated with menopausal status. The predictors of DCI and cerebral infarction were identified in a very large cohort and reflect experience from multiple institutions.
... 11 Yet, currently available treatments are plainly insufficient to prevent DCI. [16][17][18] Because DCI results from CVS that is induced by subarachnoid blood, elimination of blood from the subarachnoid space by irrigation and fibrinolytic drugs is a promising treatment approach. 4 Several smaller, nonrandomized studies and a few randomized clinical trials have been performed to assess the effect of cisternal fibrinolysis and vasodilation. ...
Article
BACKGROUND: Cerebral vasospasm leading to delayed cerebral infarction (DCI) is a central source of poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Current treatments of cerebral vasospasm are insufficient. Cisternal blood clearance is a promising treatment option. However, a generally applicable, safe, and effective method to access the cisterns of the brain is lacking. OBJECTIVE: To report on stereotactic catheter ventriculocisternostomy (STX-VCS) as a method to access the cisterns of the brain for clearance of subarachnoid hemorrhage in patients with aSAH and coiled aneurysms. METHODS: In 9 aSAH patients at high risk for DCI (Hunt and Hess grade ≥3, modified Fisher grade ≥3), access to the basal cisterns of the brain was created by STX-VCS. Fibrinolytic and/or spasmolytic lavage therapy was administered. RESULTS: STX-VCS was feasible and safe in all patients. Subarachnoid blood was rapidly cleared by irrigation with urokinase. Vasospasm occurred in 2 patients and was interrupted by irrigation with nimodipine. There was 1 fatality due to pneumogenic sepsis. Minor DCI occurred in 1 patient. Eight survived without DCI and are independent (modified Rankin score [mRS] ≤ 3) at 6 mo after aSAH. CONCLUSION: STX-VCS allows for rapid clearance of subarachnoid hemorrhage in patients with coiled aneurysms.
... These patients may be at higher risk of cerebral ischemia and subsequent cerebral infarction. UEAV has been incorporated into the BEHAVIOUR score for prediction of cerebral infarction following aSAH26 . Conversely, it is likely that ...
Article
Objective: Following aneurysmal subarachnoid hemorrhage (aSAH), prognosis is heavily affected by the presence of delayed cerebral ischemia (DCI). There is growing recognition of ultra-early angiographic vasospasm (UEAV) occurring within 48 hours of aSAH, however its relationship with DCI and ultimately prognosis remains unclear. Methods: Various databases limited to the English language through September 2016 were systematically searched. Eligible studies were those comparing UEAV with control non-UEAV outcomes and follow-up. Two independent reviewers evaluated the quality of studies and abstracted the data, with discrepancies resolved by a third. We calculated odds ratios (ORs) and 95% CIs for all outcomes using random-effects meta-analyses and performed heterogeneity analysis. Results: 4 comparative studies were selected for analysis. Pooled analysis demonstrated that UEAV when compared to no-UEAV was associated with greater proportion of rupture aneurysms sized over 12mm (38.3% vs 24.3%, P<0.00001). A significantly higher number UEAV patients had ruptured MCA aneurysms compared with patients without UEAV (29.7% vs 19.9%, P=0.005). Compared to no-UEAV, patients with UEAV were significantly associated with symptomatic cerebral vasospasm (OR 2.07, P=0.05) and DCI/infarction (OR 2.52, P=0.02). A significant association was also found between UEAV and an unfavorable outcome at follow-up (OR 1.64, P=0.03) and higher mortality (OR 2.65, P<0.00001) CONCLUSIONS: UEAV was significantly associated with symptomatic cerebral vasospasm, DCI/infarction, unfavorable outcome at follow-up and higher mortality. Patients with intracerebral hematoma, intraventricular hemorrhage (Fisher Grade IV), larger ruptured aneurysms >12mm and an MCA location were more likely to have UEAV.
... Among the larger studies, in cohorts of >500 patients, [32][33][34][35] only the work by Rosen and Macdonald unambiguously reported its applied methods and score performance measures. This score was developed using data from the landmark international study by the International Subarachnoid Aneurysm Trial group. ...
Article
Objective: To create a multidimensional tool to prognosticate long-term functional, cognitive, and quality of life outcomes after spontaneous subarachnoid hemorrhage (SAH) using data up to 48 hours after admission. Methods: Data were prospectively collected for 1,619 consecutive patients enrolled in the SAH outcome project July 1996 to March 2014. Linear models (LMs) were applied to identify factors associated with outcome in 1,526 patients with complete data. Twelve-month functional, cognitive, and quality of life outcomes were measured using the modified Rankin scale (mRS), Telephone Interview for Cognitive Status, and Sickness Impact Profile. Based on the LM residuals, we constructed the FRESH score (Functional Recovery Expected after Subarachnoid Hemorrhage). Score performance, discrimination, and internal validity were tested using the area under the receiver operating characteristic curve (AUC), Nagelkerke and Cox/Snell R(2) , and bootstrapping. For external validation, we used a control population of SAH patients from the CONSCIOUS-1 study (n = 413). Results: The FRESH score was composed of Hunt & Hess and APACHE-II physiologic scores on admission, age, and aneurysmal rebleed within 48 hours. Separate scores to prognosticate 1-year cognition (FRESH-cog) and quality of life (FRESH-quol) were developed controlling for education and premorbid disability. Poor functional outcome (mRS = 4-6) for score levels 1 through 9 respectively was present in 3, 6, 12, 38, 61, 83, 92, 98, and 100% at 1-year follow-up. Performance of FRESH (AUC = 0.90), FRESH-cog (AUC = 0.80), and FRESH-quol (AUC = 0.78) was high. External validation of our cohort using mRS as endpoint showed satisfactory results (AUC = 0.77). To allow for convenient score calculation, we built a smartphone app available for free download. Interpretation: FRESH is the first clinical tool to prognosticate long-term outcome after spontaneous SAH in a multidimensional manner. Ann Neurol 2016;80:46-58.
... It should be noted that higher age of the patients in the "current" cohort designated rather higher risk for unfavorable outcome and cerebral infarction. The strong association between these factors is well acknowledged 24 and could be also shown in our multivariate analysis (p=0.005, Table 2). ...
... Moreover, the created risk score passed through internal validation using receiver operating characteristic curve, the Hosmer-Lemeshow test for goodness of fit for logistic regression models, and widely used bootstrapping method. [14][15][16] In addition, the SAH patients with and without ICH were correlated with regard to the features of clinical course. The differences between continuous variables were analyzed using the Student t-test (for normally distributed data), the Mann-Whitney U test (for nonnormally distributed data) or analysis of variance test; associations between categorical variables were analyzed using x 2 test or Fisher exact test, as appropriate. ...
Article
BACKGROUND Along with subarachnoid hemorrhage (SAH), a ruptured aneurysm may also cause an intracerebral hematoma (ICH), which negatively impacts the functional outcome of SAH. OBJECTIVE To identify independent risk factors of aneurysmal ICH. METHODS Six hundred thirty-two consecutive patients with aneurysmal SAH treated at our institution from January 2005 to December 2012 were eligible for this study. Demographic parameters and preexisting comorbidities of patients, as well as various clinical and radiographic characteristics of SAH were correlated with the incidence and volume of aneurysmal ICH. RESULTS One hundred fifty-five patients (25%) had ICH on initial computed tomography with a mean volume of 26.7 mL (±26.8 mL). Occurrence and volume of ICH were associated with the location (distal anterior or middle cerebral artery >proximal anterior cerebral or internal carotid artery >posterior circulation, P < .001/P < .001) and size (>12 mm, P = .026/P < .001) of the ruptured aneurysm. Vascular risk factors independently increased the risk of ICH as well (arterial hypertension: odds ratio [OR] = 1.62, P = .032; diabetes mellitus: OR = 3.06, P = .009), while the use of aspirin (P = .037) correlated with the volume of ICH. The predictors of ICH were included into a risk score (0-9 points) that strongly predicted the occurrence of ICH (P = .01). Poor functional outcome after SAH was independently associated with the occurrence of ICH (P = .003, OR = 2.77) and its volume (P = .001, OR = 1.07 per-mL-increase). CONCLUSION Aneurysmal ICH is strongly associated with poorer functional outcome and seems to be predictable even before the bleeding event. The proposed risk factors for aneurysmal ICH require further validation and may be considered for treatment decisions regarding unruptured intracranial aneurysms.
... Hence, extracellular mitochondria in CSF may be a candidate biomarker that connects early brain injury mechanisms with recovery after SAH. Whether and how extracellular mitochondria may mechanistically connect to delayed vascular sequelae of SAH (vasospasm, perturbations in hemostasis and fibrinolysis, cerebral ischemia, etc) 15,16 remain to be determined. Fifth, mitochondria are highly dynamic entities with highly responsive profiles of fission and ...
Article
Full-text available
Background and purpose: Recent studies suggest that extracellular mitochondria may be involved in the pathophysiology of stroke. In this study, we assessed the functional relevance of endogenous extracellular mitochondria in cerebrospinal fluid (CSF) in rats and humans after subarachnoid hemorrhage (SAH). Methods: A standard rat model of SAH was used, where an intraluminal suture was used to perforate a cerebral artery, thus leading to blood extravasation into subarachnoid space. At 24 and 72 hours after SAH, neurological outcomes were measured, and the standard JC1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolylcarbocyanineiodide) assay was used to quantify mitochondrial membrane potentials in the CSF. To further support the rat model experiments, CSF samples were obtained from 41 patients with SAH and 27 control subjects. Mitochondrial membrane potentials were measured with the JC1 assay, and correlations with clinical outcomes were assessed at 3 months. Results: In the standard rat model of SAH, extracellular mitochondria was detected in CSF at 24 and 72 hours after injury. JC1 assays demonstrated that mitochondrial membrane potentials in CSF were decreased after SAH compared with sham-operated controls. In human CSF samples, extracellular mitochondria were also detected, and JC1 levels were also reduced after SAH. Furthermore, higher mitochondrial membrane potentials in the CSF were correlated with good clinical recovery at 3 months after SAH onset. Conclusions: This proof-of-concept study suggests that extracellular mitochondria may provide a biomarker-like glimpse into brain integrity and recovery after injury.
... Cerebral infarction occurs frequently in the middle-aged and elderly people. According to the report of Jabbarli et al (3), there are approximately 600,000 new cerebral infarction patients worldwide in 2015. With the growth of aging population, incidence of cerebral infarction shows an increasing trend (4). ...
Article
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Therapeutic efficacy of the use of oral atorvas­tatin in the treatment of patients with aspiration pneumonia complicated with cerebral infarction was investigated. Three hundred and fourteen cerebral infarction patients complicated with aspiration pneumonia who were admitted to the emer­gency department of Beijing Chaoyang Hospital Jingxi Branch from May 2015 to July 2017 were retrospectively analyzed. Among them, 160 patients who took atorvastatin were treated as observation group, and the remaining 154 patients were the control group. Patients were given basic treatment after diagnosis, and atorvastatin was also used for patients in the observation group. Venous blood was extracted to detect blood lipids and inflammatory cytokines. Patients were followed up for a period of six months, and the mortality was recorded. After treatment, blood lipid function and inflam­matory factors in both groups were significantly improved (P<0.05). Hospital stay in the observation group (86.88%) was significantly shorter than that in the control group (76.33%) (P<0.01). After treatment, levels of TC, LDL, TG and CRP in the observation group (86.25%) were significantly lower than those in the control group (76.32%) (P=0.01). However, after treatment, level of HDL-C in the observation group (11.88%) was significantly higher than that in the control group (23.38%) (P=0.01). After treatment, levels of IL-6, IL-8 and TNF-α in the observation group were significantly lower than those in the control group (P<0.01). Total effective rate in the observation group was significantly higher than that of the control group (P=0.01). Total death rate in the obser­vation group was significantly lower than that in the control group (P=0.02). In conclusion, atorvastatin is effective in the treatment of cerebral infarction patients complicated with aspiration pneumonia.
... Cerebral infarction is one of the most common causes of brain death, while resting cerebral infarction is one of the more specific types of cerebral infarction [1]. Sometimes, patients were not found to have more significant clinical signs, but the images of the brain will show that patients have had a pathological cerebral infarction [2]. These cases of silent cerebral infarcts are called as Silent Brain Infarction (SBI). ...
... The mechanisms underlying CVS remain unclear; it may be multifactorial and involve a complicated pathological process. Potential causes of CVS are as follows: 1. mechanical stimulation such as damage, compression or stretching of the blood vessels during surgery, leading to the blood owing into the subarachnoid space and subsequent occurrence of CVS occurs [17]; 2. vascular wall injury caused by compression of the vascular wall and vascular wall malnutrition [18]; 3. damage caused by the oxidation of hemoglobin to methemoglobin and release of oxygen free radicals [19]; 4. constriction of the blood vessels caused by vasoactive substances [20]; 5. increased intracranial pressure, the overdose of dehydration drugs and insu cient supply of blood volume [21]; and 6. in ammation and immune reactions of blood vessel walls [6,22,23]. The common nal pathway arising from all the above factors stated is a change in the permeability of smooth muscle cells in the blood vessels, an increase in calcium in ux and release of calcium ion from intracellular calcium stores, leading to an overload of free calcium in the cytosol [24]. ...
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Background:Cerebral vasospasm (CVS) is a serious neurosurgical complication. This retrospective study was performed to analyze if nimodipine can improve prognosis and reduces ischemia secondary to delayed CVS after intracranial tumor surgery. Methods:Retrospective analysis of 94 patients with an anterior cranial fossa tumor and underwent intracranial tumor surgery was performed, with 42 cases treated with normal saline and 52 cases treated with nimodipine solution. Transcranial Doppler ultrasonography was used to measure velocity in the middle cerebral artery (MCA) and the distal extracranial internal carotid artery (eICA). An examination was conducted 1 day before surgery and 1, 3, 5, 7, and 14 days after surgery. Follow-up was performed using the Glasgow Outcome Scale (GOS) 3 months after discharge. Results:We showed that in the nimodipine group, CVS occurred in 13 (25%) patients who did not have CVS in the first three days after operation; nine patients had CVS between 4 and 7 days, and 4 had CVS between 8 and 14 days. In the normal saline group, nineteen (45%) patients had CVS, 3 presented with CVS within 3 days, 11 between 4-7 days and 5 between 8-14 days. A significant difference in the occurrence of CVS was observed between the two groups. Preoperative and postoperative the MCA velocities were compared, revealing a significant change in the normal saline group (P < 0.05) but not in the nimodipine group. Furthermore, significant differences in the outcome were observed between the two groups at the 3-month follow-up (P < 0.05). Conclusions:Nimodipine markedly improves prognosis and significantly reduces ischemia secondary to delayed CVS after intracranial tumor surgery, as well as the risks of mortality and morbidity.
... Most studies that have assessed this association have not revealed a significant correlation between functional outcome after aneurysmal SAH and sex. [57][58][59] Although prior epidemiological literature has indicated that females are more likely to die from SAH than males, supporting a significant sex difference in mortality, 60 subsequent literature largely indicated no significant difference in outcome. One single-center study (n=617) found no significant difference in adjusted odds of poor outcome (modified Rankin Scale [mRS] score 4-6) for females compared with males (OR, 0.71 [95% CI, 0.45-1.11]) ...
Article
Sex differences in cerebral aneurysm occurrence and characteristics have been well described. Although sex differences in outcomes following ischemic stroke have been identified, the effect of sex on outcomes following hemorrhagic stroke, and in particular, aneurysm treatment has been less studied. We describe the current state of knowledge regarding the impact of sex on treatment and outcomes of cerebral aneurysms. Although prior studies suggest that aneurysm prevalence and progression may be related to sex, we did not find clear evidence that outcomes following subarachnoid hemorrhage vary based on sex. Last, we identify areas for future research that could enhance understanding of the role sex plays in this context.
... Cerebral infarction is especially prevalent in older adults [4] . In 2015 alone, there was 600,000 cases of CI worldwide [5] . Cerebral infarction generally results in poor quality of life and reduced physical function. ...
Article
Objective: While it is known that exercise therapy can improve physical and emotional function in cerebral infarction (CI) patients, few studies have examined how well this would be accepted by older adults in China. Methods: In this study, the feasibility of recruiting and assessing health-related quality of life and physical function in older Chinese adults with cerebral infarction was assessed. Specific aims of the study were to evaluate the feasibility of recruiting older adults, with and without CI, from three different locations/settings in China; Compare the quality of life and physical function measures between CI and control subjects; Propose future larger randomized controlled studies of aerobic and resistance exercise training in both human and animal models after CI. Results: Overall, 66/275 (24.0%) surveys that were sent to older Chinese adults were returned and evaluated. Of those surveys returned, 18 (27%) met the study inclusion and exclusion criteria. Consequently, the results of this feasibility study indicate there is a recruitment yield (number of subject contacted/number of subjects who qualified for study) of 6.5%. These number varied at the different sites/settings, but the highest recruitment yield was seen in hospitalized patients. Despite small sample sizes, there were statistically significant differences in health-related quality of life and physical function between CI patients and control subjects. Conclusion: This feasibility study demonstrated that it is possible to successfully recruit CI patients for an exercise intervention study as well as to perform important assessments of health-related quality of life and physical function. Further randomized controlled trials, in humans and animal models, will be needed determine if aerobic and/or resistance exercise training can improve health and physical function in older CI patients. Additional studies will be needed to determine the specific mechanisms responsible for the benefits see with aerobic and resistance training.
... It represents a medical catastrophe as it confers a high rate of poor neurological outcome and death [1]. Secondary brain injury contributes significantly to poor outcome [2,3]. In contrast to brain injury incurred during the initial bleeding event, secondary brain injury is potentially amenable to medical treatments. ...
Article
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Background Delayed cerebral infarction (DCI) is a major cause of death and poor neurological outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Direct intrathecal therapies with fibrinolytic and spasmolytic drugs have appeared promising in clinical trials. However, access to the subarachnoid space for intrathecal drug administration is an unsolved problem so far, especially in patients with endovascular aneurysm securing. We investigate a therapy protocol based on stereotactic catheter ventriculocisternostomy (STX-VCS), a new approach to overcome this problem. The primary objective of this study is to assess whether cisternal lavage with urokinase, nimodipine, and Ringer’s solution administered via a stereotactically implanted catheter into the basal cisterns (= investigational treatment (IT)) is safe and improves neurological outcome in patients with aSAH. Methods This is a randomized, controlled, parallel-group, open-label phase II trial. Fifty-four patients with severe aSAH (WFNS grade ≥ 3) will be enrolled at one academic tertiary care center in Southern Germany. Patients will be randomized at a ratio of 1:1 to receive either standard of care only or standard of care plus the IT. The primary endpoint is the proportion of subjects with a favorable outcome on the Modified Rankin Scale (defined as mRS 0–3) at 6 months after aSAH. Further clinical and surrogate outcome parameters are defined as secondary endpoints. Discussion New approaches for the prevention and therapy of secondary brain injury in patients with aSAH are urgently needed. We propose this RCT to assess the clinical safety and efficacy of a novel therapy protocol for intrathecal administration of urokinase, nimodipine, and Ringer’s solution. Trial registration Deutsches Register Klinischer Studien (German Clinical Trials Register), DRKS00015645. Registered on 8 May 2019
... UEAV has already been included in the BEHAVIOR score for the prediction of DCI in SAH patients. 33 On the basis of our findings and increasing evidence in the literature, this can also justify the inclusion of UEAV in vasospasm prediction scores. Future research should be undertaken to investigate whether active screening for UEAV and aggressive early therapy could attenuate DCVS, reduce DCI, and improve patient outcome in SAH patients. ...
Article
Full-text available
BACKGROUND Preliminary evidence exists that ultra-early angiographic vasospasm (UEAV) after aneurysmal subarachnoid hemorrhage (SAH) is associated with delayed cerebral vasospasm (DCVS), delayed cerebral ischemia (DCI), and poor functional outcome. Typically, detection of UEAV has been based on admission radiological imaging. OBJECTIVE To elucidate the occurrence of the phenomenon of UEAV during treatment in SAH patients. METHODS A total of 206 consecutive patients underwent either endovascular or microsurgical treatment in a hybrid operating room within 48 h after SAH. Time to DCVS and DCI, and poor functional outcome (both binary) were analyzed using Cox proportional-hazards and logistic regression models. We examined both univariable models (admission and periinterventional UEAV) and multivariable models (backward variable selection, including further known and suspected risk factors). RESULTS For UEAV detected in 33 patients (16%), 10 were admission and periinterventional and 23 periinterventional only. Both admission and periinterventional UEAV significantly increased the risk of DCVS (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.2–2.3, P = .001), DCI (odds ratio [OR] 5.9, CI 1.7-25.1, P = .001), and poor functional outcome (OR 4.7, CI 1.7-13.4, P = .004). Clipping, female sex, and higher Barrow Neurological Institute (BNI) scale increased the hazard for DCVS and the probability for DCI, whereas increasing patient age, poor initial World Federation of Neurological Surgeons (WFNS) grade, and intraparenchymal hemorrhage increased the probability for poor functional outcome. CONCLUSION Detection of admission or periinterventional UEAV poses high risk of DCVS, DCI, and poor outcome after SAH. Therefore, periinterventional UEAV should be considered an important warning sign that warrants both early monitoring and aggressive therapy.
... In fact, DC remains mostly an ultima ratio against intractable intracranial hypertension, which is basically the consequence of severe early brain injury and secondary ischemic complications after SAH. At the same time, these causal processes evoking DC are also acknowledged as strong outcome predictors of SAH (Jabbarli et al., 2015a;Jabbarli et al., 2015b). As noted in a recent meta-analysis on DC in SAH (Alotaibi et al., 2017), due to the lack of robust control groups, the effect of DC on functional outcomes versus that of other interventions for refractory intracranial hypertension is still unknown. ...
Article
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The prognosis of patients with aneurysmal subarachnoid haemorrhage requiring decompressive craniectomy is usually poor. Proper selection and early performing of decompressive craniectomy might improve the patients' outcome. We aimed at developing a risk score for prediction of decompressive craniectomy after aneurysmal subarachnoid haemorrhage. All consecutive aneurysmal subarachnoid haemorrhage cases treated at the University Hospital of Essen between January 2003 and June 2016 (test cohort) and the University Medical Center Freiburg between January 2005 and December 2012 (validation cohort) were eligible for this study. Various parameters collected within 72 h after aneurysmal subarachnoid haemorrhage were evaluated through univariate and multivariate analyses to predict separately primary (PrimDC) and secondary decompressive craniectomy (SecDC). The final analysis included 1376 patients. The constructed risk score included the following parameters: intracerebral ('Parenchymal') haemorrhage (1 point), 'Rapid' vasospasm on angiography (1 point), Early cerebral infarction (1 point), aneurysm Sac > 5 mm (1 point), clipping (' S urgery', 1 point), age U nder 55 years (2 points), Hunt and Hess grade ≥ 4 ('Reduced consciousness', 1 point) and External ventricular drain (1 point). The PRESSURE score (0-9 points) showed high diagnostic accuracy for the prediction of PrimDC and SecDC in the test (area under the curve = 0.842/0.818) and validation cohorts (area under the curve = 0.903/0.823), respectively. 63.7% of the patients scoring ≥6 points required decompressive craniectomy (versus 12% for the PRESSURE < 6 points, P < 0.0001). In the subgroup of the patients with the PRESSURE ≥6 points and absence of dilated/fixed pupils, PrimDC within 24 h after aneurysmal subarachnoid haemorrhage was independently associated with lower risk of unfavourable outcome (modified Rankin Scale >3 at 6 months) than in individuals with later or no decompressive craniectomy (P < 0.0001). Our risk score was successfully validated as reliable predictor of decompressive craniectomy after aneurysmal subarachnoid haemorrhage. The PRESSURE score might present a background for a prospective randomized clinical trial addressing the utility of early prophylactic decompressive craniectomy in aneurysmal subarachnoid haemorrhage.
... The mechanisms underlying CVS remain unclear; it may be multifactorial and involve a complicated pathological process. Potential causes of CVS are as follows: 1. mechanical stimulation such as damage, compression or stretching of the blood vessels during surgery, leading to the blood owing into the subarachnoid space and subsequent occurrence of CVS occurs [17]; 2. vascular wall injury caused by compression of the vascular wall and vascular wall malnutrition [18]; 3. damage caused by the oxidation of hemoglobin to methemoglobin and release of oxygen free radicals [19]; 4. constriction of the blood vessels caused by vasoactive substances [20]; 5. increased intracranial pressure, the overdose of dehydration drugs and insu cient supply of blood volume [21]; and 6. in ammation and immune reactions of blood vessel walls [6,22,23]. The common nal pathway arising from all the above factors stated is a change in the permeability of smooth muscle cells in the blood vessels, an increase in calcium in ux and release of calcium ion from intracellular calcium stores, leading to an overload of free calcium in the cytosol [24]. ...
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Full-text available
Background:Cerebral vasospasm (CVS) is a serious neurosurgical complication. This retrospective study was performed to analyze if nimodipine can improve prognosis and reduces ischemia secondary to delayed CVS after intracranial tumor surgery. Methods:Retrospective analysis of 94 patients with an anterior cranial fossa tumor and underwent intracranial tumor surgery was performed, with 42 cases treated with normal saline and 52 cases treated with nimodipine solution. Transcranial Doppler ultrasonography was used to measure velocity in the middle cerebral artery (MCA) and the distal extracranial internal carotid artery (eICA). An examination was conducted 1 day before surgery and 1, 3, 5, 7, and 14 days after surgery. Follow-up was performed using the Glasgow Outcome Scale (GOS) 3 months after discharge. Results:We showed that in the nimodipine group, CVS occurred in 13 (25%) patients who did not have CVS in the first three days after operation; nine patients had CVS between 4 and 7 days, and 4 had CVS between 8 and 14 days. In the normal saline group, nineteen (45%) patients had CVS, 3 presented with CVS within 3 days, 11 between 4-7 days and 5 between 8-14 days. A significant difference in the occurrence of CVS was observed between the two groups. Preoperative and postoperative the MCA velocities were compared, revealing a significant change in the normal saline group (P < 0.05) but not in the nimodipine group. Furthermore, significant differences in the outcome were observed between the two groups at the 3-month follow-up (P < 0.05). Conclusions:Nimodipine markedly improves prognosis and significantly reduces ischemia secondary to delayed CVS after intracranial tumor surgery, as well as the risks of mortality and morbidity.
... 10,11 Several prediction models are available to identify patients who are at risk for CVS and DCI. [12][13][14][15][16][17] A simple prediction tool is the Barrow Neurological Institute (BNI) score. 18 It assesses the point of maximal thickness of subarachnoid blood particularly across the cistern or fissure allocating patients into five groups. ...
Article
Background: The Barrow Neurological Institute (BNI) score, measuring maximal thickness of aneurysmal subarachnoid hemorrhage (aSAH), has previously shown to predict symptomatic cerebral vasospasms (CVSs), delayed cerebral ischemia (DCI), and functional outcome. Objective: To validate the BNI score for prediction of above-mentioned variables and cerebral infarct and evaluate its improvement by integrating further variables which are available within the first 24 h after hemorrhage. Methods: We included patients from a single center. The BNI score for prediction of CVS, DCI, infarct, and functional outcome was validated in our cohort using measurements of calibration and discrimination (area under the curve [AUC]). We improved it by adding additional variables, creating a novel risk score (measure by the dichotomized Glasgow Outcome Scale) and validated it in a small independent cohort. Results: Of 646 patients, 41.5% developed symptomatic CVS, 22.9% DCI, 23.5% cerebral infarct, and 29% had an unfavorable outcome. The BNI score was associated with all outcome measurements. We improved functional outcome prediction accuracy by including age, BNI score, World Federation of Neurologic Surgeons, rebleeding, clipping, and hydrocephalus (AUC 0.84, 95% CI 0.8-0.87). Based on this model we created a risk score (HATCH-Hemorrhage, Age, Treatment, Clinical State, Hydrocephalus), ranging 0 to 13 points. We validated it in a small independent cohort. The validated score demonstrated very good discriminative ability (AUC 0.84 [95% CI 0.72-0.96]). Conclusion: We developed the HATCH score, which is a moderate predictor of DCI, but excellent predictor of functional outcome at 1 yr after aSAH.
... The mechanisms underlying CVS remain unclear; it may be multifactorial and involve a complicated pathological process. Potential causes of CVS are as follows: 1. mechanical stimulation such as damage, compression or stretching of the blood vessels during surgery, leading to the blood owing into the subarachnoid space and subsequent occurrence of CVS occurs [17]; 2. vascular wall injury caused by compression of the vascular wall and vascular wall malnutrition [18]; 3. damage caused by the oxidation of hemoglobin to methemoglobin and release of oxygen free radicals [19]; 4. constriction of the blood vessels caused by vasoactive substances [20]; 5. increased intracranial pressure, the overdose of dehydration drugs and insu cient supply of blood volume [21]; and 6. in ammation and immune reactions of blood vessel walls [7,22,23]. The common nal pathway arising from all the above factors stated is a change in the permeability of smooth muscle cells in the blood vessels, an increase in calcium in ux and release of calcium ion from intracellular calcium stores, leading to an overload of free calcium in the cytosol [24]. ...
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Background Cerebral vasospasm (CVS) is a serious neurosurgical complication. This retrospective study was performed to analyze if nimodipine can improve prognosis and reduces ischemia secondary to delayed CVS after intracranial tumor surgery. Methods Retrospective analysis of 94 patients with an anterior cranial fossa tumor and underwent intracranial tumor surgery was performed, with 42 cases treated with normal saline and 52 cases treated with nimodipine solution. Transcranial Doppler ultrasonography was used to measure velocity in the middle cerebral artery (MCA) and distal extracranial internal carotid artery (eICA). An examination was conducted 1 day before surgery and 1, 3, 5, 7, and 14 days after surgery. Follow-up was performed using the Glasgow Outcome Scale (GOS) 3 months after discharge. Results We showed that in the nimodipine group, CVS occurred in 13 (25%) patients who did not have CVS in the first three days after operation; nine patients had CVS between 4 and 7 days, and 4 had CVS between 8 and 14 days. In the normal saline group, nineteen (45%) patients had CVS, 3 presented with CVS within 3 days, 11 between 4–7 days and 5 between 8–14 days. A significant difference in the occurrence of CVS was observed between the two groups. Preoperative and postoperative MCA velocities were compared, revealing a significant change in the normal saline group (P < 0.05) but not in the nimodipine group. Furthermore, significant differences in the outcome were observed between the two groups at the 3-month follow-up (P < 0.05). Conclusions Nimodipine markedly improves prognosis and significantly reduces ischemia secondary to delayed CVS after intracranial tumor surgery, as well as the risks of mortality and morbidity.
... Although VG was developed by two early predictors, and available for risk stratification at the time after SAH, the AUC was not large according to results from recent study.15 Dengler et al 15 retrospectively reviewed 423 consecutive patients with aSAH and showed that the combined scores had no superiority to the sin-Other risk stratification scores usually have a large range of scores, which may inconvenience practitioners and limit their applicability.17,26,30,31 Unlike other risk stratification scores, we use a dichotomy to divide risk factors into categorical variables (eg, high WFNS and low WFNS), and the variables were only limited to those available within 72 hours after aSAH. ...
Article
Full-text available
Background and purpose: The aim of this study is to identify the early predictors for delayed cerebral ischemia (DCI) and develop a risk stratification score by focusing on the early change after aneurysmal subarachnoid hemorrhage (aSAH). Methods: The study retrospectively reviewed aSAH patients between 2014 and 2015. Risk factors within 72 hours after aSAH were included into univariable and multivariable logistic regression analysis to screen the independent predictors for DCI and to design a risk stratification score. Results: We analyzed 702 aSAH patients; four predictors were retained from the final multivariable analysis: World Federation of Neurosurgical Societies scale (WFNS; OR = 4.057, P < .001), modified Fisher Scale (mFS; OR = 2.623, P < .001), Subarachnoid Hemorrhage Early Brain Edema Score (SEBES; OR = 1.539, P = .036), and intraventricular hemorrhage (IVH; OR = 1.932, P = .002). According to the regression coefficient, we created a risk stratification score ranging from 0 to 7 (WFNS = 3, mFS = 2, SEBES = 1, and IVH = 1). The new score showed a significantly higher area under curve (0.785) compared with other scores (P < .001). Conclusion: The early DCI score provides a practical method at the early 72 hours after aSAH to predict DCI.
... 1,2 In patients surviving the initial impact of SAH, DCI is considered the major preventable cause of poor outcome. 3 Therefore, the proper management of DCI is the cornerstone of SAH guidelines. 4 The current literature adheres to a multifactorial nature of DCI, considering different causal factors like EBI, neuroinflammatory processes, cortical spreading depolarization, microthrombosis, and microcirculatory dysfunction with loss of autoregulation. ...
Article
Objective: Delayed cerebral ischemia (DCI) is strongly associated with poor outcome after subarachnoid hemorrhage (SAH). Cerebral vasospasm is a major contributor to DCI and requires special attention. To evaluate the effect of vasospasm management on SAH outcome, we performed a pooled analysis of 2 observational SAH cohorts. Materials: Data from 2 institutional databases with consecutive patients with SAH treated between 2005 and 2012 were pooled. The effect of 2 institutional standards of conservative and endovascular vasospasm treatment (EVT) on the rates of DCI (new cerebral infarcts not visible on the post-treatment imaging) and unfavorable outcome (modified Rankin Scale score >2) at 6 months follow-up was analyzed. Results: The final analysis included 1,057 patients with SAH. There was no difference regarding demographic (age and sex), clinical (Hunt & Hess grades, acute hydrocephalus, treatment modality, and infections), and radiographic (Fisher grades and aneurysm location) characteristics of the populations. However, there was a significant difference in the rate (24.4% [121/495] vs 14.4% [81/562], p < 0.0001) and timing (first treatment on day 6 vs 8.9 after SAH, p < 0.0001) of EVT. The rates of DCI (20.8% vs 29%, p = 0.0001) and unfavorable outcome (44% vs 50.6%, p = 0.04) were lower in the cohort with more frequent and early EVT. Multivariate analysis confirmed independent effect of EVT standard on DCI risk and outcome. Conclusions: A preventive strategy utilizing frequent and early EVT seems to reduce the risk of DCI in SAH patients and improve their functional outcome. We recommend prospective evaluation of the value of preventive EVT strategy on SAH. Classification of evidence: This study provides Class III evidence that for patients with SAH, a frequent and early EVT to treat vasospasm reduces the risk of DCI and improves functional outcome.
... The aim of our study was to find the predictive variables for CVS in AVM-associated hemorrhage. In aneurysmal SAH, CVS and CI are common [3][4][5][6][7], owing to the amount of subarachnoid blood [1,[7][8][9][10][11]. AVMs show differences in hemorrhage pattern and clinical course in relation to bleeding pattern (SAH, ICH), their location, and angioarchitecture [12]. Although SAH is one of the bleeding pattern in AVM-associated hemorrhage [13,14], CVS thereafter is rarely described in the pertaining literature and limited to a few case reports mostly associated with intraventricular hemorrhage [15][16][17][18]. ...
Article
Objective: Cerebral vasospasm (CVS) after a ruptured arteriovenous malformation (AVM) is rarely reported. This study is aimed at evaluating the predictive variables in AVM hemorrhage for CVS. Methods: A total of 160 patients with ruptured AVMs were admitted to our neurosurgical department from 2002 to 2018. The frequency of cerebral vasospasm after AVM hemorrhage and the impact of AVM-associated aneurysms were evaluated. We compared different bleeding patterns, such as intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) or a combination of both (ICH + SAH) and evaluated predictive variables for outcome in last follow-up. Results: A total of 62 (39%) patients had AAA, mostly located prenidal (75.8%). AVMs with ruptured aneurysms often resulted in ICH with SAH component (p < 0.001). Eighty-two patients (51%) presented a SAH component, and CVS occurred in 6 patients (7.3%), mostly due to a ruptured infratentorial AVM (p < 0.03). Infratentorial location and the amount of SAH component (p < 0.001) predicted the incidence of CVS significantly. Cerebral infarction was significantly associated with CVS (p < 0.02). Conclusion: SAH component and infratentorial location of ruptured AVMs may harbor a higher risk for CVS. Follow-up with angiographic imaging should be considered in patients with infratentorial AVM hemorrhage and delayed neurologic deterioration to rule out CVS.
... On the contrary, a retrospective Cuban case-control study found female gender to be a risk factor for poor outcome [51]. A recently suggested scoring system to predict poor clinical outcome at discharge and 6 months, known as the BEHAVIOR score, takes into consideration parameters such as Fisher grade >3 (1 point), elderly patients (age>55 years, 1 point), Hunt and Hess grade >4 (1 point), acute hydrocephalus requiring external drainage (1 point), vasospasm on initial angiogram (3 points), intracranial pressure elevation >20 mmHg (3 points), and treatment of multiple aneurysms (1 point), but does not take sex into account [52]. Although it is known that mortality is higher in women compared to men, conflicting results exist on the effect of female gender on functional outcome among survivors, with most studies suggesting that sex difference has no effect on functional outcome. ...
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Intracranial aneurysms are defined as pathological dilatations of cerebral arteries and rupture of intracranial aneurysms leads to subarachnoid hemorrhage (SAH). The goal of this review was to outline the sex differences in the formation and progression of intracranial aneurysms as well as sex-related differences in incidence and outcome of SAH. The literature review was performed using PubMed with a combination of these search terms: "subarachnoid hemorrhage," "incidence," "outcome," "sex," "gender," "male," "female," "experimental," "mice," and "rats." Studies written in English were used. Female sex is thought to be a risk factor for aneurysm formation, especially in postmenopausal age populations, suggesting the potential protective involvement of sex steroids. Female sex is also considered a risk factor for SAH occurrence. Although incidence and mortality are confirmed to be higher in females in most studies, they elucidated no clear differences in the functional outcome among SAH survivors. The effect of gender on the pathophysiology of SAH is not very well understood; nevertheless, the majority of pre-clinical studies suggest a beneficial effect of sex steroids in experimental SAH. Moreover, conflicting results exist on the role and effect of hormone replacement therapies and oral contraceptive pills on the incidence and outcome of human SAH. Sex differences exist in the formation of aneurysms as well as the incidence and mortality of SAH. Potential therapeutic effects of sex steroids have been replicated in many animal studies, but their potential use in the treatment of acute SAH in human populations needs more future study.
Article
Subarachnoid hemorrhage (SAH) is a devastating form of stroke. Approximately one in four patients develop progressive neurological deterioration and silent infarction referred to as delayed cerebral ischemia (DCI). DCI is a complex, multifactorial secondary brain injury pattern and its pathogenesis is not fully understood. We aimed to study the relationship between cerebral blood flow (CBF) and neuronal activity at both the cortex and in scalp using electroencephalography (EEG) in poor-grade SAH patients undergoing multimodality intracranial neuromonitoring. Twenty patients were included, of whom half had DCI median 4.7 days (interquartile range (IQR): 4.0-5.6) from SAH bleed. The rate of decline in regional cerebral blood flow (rCBF) was significant in both those with and without DCI and occurred between days 4 and 7 post-SAH. The scalp EEG alpha-delta ratio declined early in those with DCI. In the group without DCI, CBF and cortical EEG alpha-delta ratio were correlated (r = 0.53; p < 0.01) and in the group without DCI, inverse neurovascular coupling was observed at CPP < 80 mmHg. We found preliminary evidence that as patients enter the period of highest risk for the development of DCI, the absence of neurovascular coupling may act as a possible pathomechanism in the development of ischemia following SAH.
Article
Delayed Cerebral Infarction (DCI) due to Cerebral Vasospasm (CVS) is an important contributor to poor outcome after aneurysmal subarachnoid haemorrhage (aSAH). Despite established risk factors CVS and DCI are unpredictable at the individual patient level. Efficient treatments are lacking. We report a novel rescue therapy for DCI: Access to the basal cisterns by stereotactic catheter ventriculocisternostomy (STX-VCS) and direct cisternal application of the spasmolytic agent Nimodipine. On the basis of individual treatment decisions three aSAH patients who developed CVS underwent STX-VCS. Continuous lavage with Nimodipine was performed. CVS was assessed by daily transcranial doppler ultrasonography. Neurological outcome at 3 months was assessed by modified Rankin scale. STX-VCS was performed without complications in all patients. CVS rapidly resolved upon cisternal application of Nimodipine. CVS recurred in two patients upon interruption of Nimodpine application and resolved upon restart of Nimodipine. DCI did not occur in all three cases. STX-VCS and cisternal Nimodipine application is a novel rescue therapy for CVS treatment and DCI-prevention in patients with aSAH.
Article
Objectives: Our aim was to develop and validate a procedure-related neurological complications (PNC) risk score for individual elderly patients with rupture intracranial aneurysms (RIAs) undergoing endovascular treatment (EVT). Methods: Preoperatively collected data, including clinical, lesion, and procedure characteristics of consecutive elderly patients (≥ 60 years), were used to develop a PNC risk predictive score based on the coefficients (β) of a multivariable logistic regression analysis. The PNC included intraprocedural rupture, thromboembolic events, and rebleeding within 30 days after EVT. Results: Overall, 520 elderly patients who underwent EVT were enrolled. At 30 days, the PNC rate was 13.08%. Six risk factors were independently associated with PNC and comprised the PNC score (PNC score, 0-16 points): hypertension (2 point), Hunt-Hess grade ≥ 4 (3 points), Fisher grade ≥ 3 (2 points), wide-necked aneurysm (2 points), with a bleb on the aneurysm sac (3 points), and aneurysm size (3-10 mm, 1 point; < 3 mm, 4 points). The PNC score model predicted the risk of PNC at a sensitivity of 63.22% and specificity of 84.79%. Moreover, the PNC score demonstrated significant discrimination (area under curve, 0.799; p <0.001) and calibration (Hosmer-Lemeshow test, p=0.319). Excellent prediction, discrimination, and calibration properties were reproduced by the internal validation group with bootstrapping techniques. Conclusions: The PNC score can be an easily applicable tool for predicting the risk of PNC for individual elderly patients with RIAs undergoing EVT. Our study provides large cases based evidence supporting the integration of individual clinical, lesion, and procedure characteristics to predict PNC risk.
Article
Objective: To study the influence of butyphthalide combined with urinary kallikrein in acute cerebral infarction (ACI) treatment on neuro-cytokines and indicators of vascular endothelial function, observe the curative effect and adverse effects, and discuss its safety and feasibility. Method: 110 ACI patients were chosen as the objects, and classified into observation group (55 cases) and control group (55 cases) according to the method of random number table. Butyphthalide injection combined with urinary kallikrein was adopted for the observation group based on conventional treatment, while cinepazide maleate injection combined with alprostadil injection was applied for the control group based on conventional treatment. The following indicators of both groups were compared before and after treatment: neurotrophic factor (NTF), nerve growth factor (NGF), neuron specific enolase (NSE); content of CXC chemotactic factor ligand 16 (CXCL16), soluble CD ligand (CD40L), Fibulin-5 and high mobility group box B1 (HMGB1); the content of indicators of vascular endothelial function including plasma endothelin -1 (ET-1) and no therapeutic effects and adverse effects were recorded. Results: NSE of both groups after treatment decreased obviously, and the content of NTF and NGF increased obviously. NSE content of observation group was lower than that of control group. NTF content and NGF content of observation group were higher than those of control group. The differences had statistical significance (P < 0.05). The levels of CXCL16, CD40L, Fibulin-5 and HMGB1 declined obviously, compared with pre-treatment, and the levels of observation groups were significantly lower than those of control grip. The differences had statistical significance (P < 0.05). ET-1 level rose significantly after treatment, and NO level declined obviously after treatment. ET-1 level of observation group was significantly higher than that of control group, and NO level of observation group was significantly lower than that of control group. The difference had statistical significance (P < 0.05). Clinical effect of observation group was significantly higher than that of control group. The difference had statistical significance (P < 0.05). The comparison difference of both groups in the occurrence rate of adverse effects had no statistical significance (P > 0.05). Conclusion: The application of butyphthalide combined with urinary kallikrein in ACI treatment can effectively inhibit secretion and release of neuro-cytokines, and improve patients’ vascular endothelial function, with significant treatment effect and high safety. Therefore, it deserves to be promoted clinically.
Article
Objective: Decompressive craniectomy (DC) may become a life-saving measure for patients with subarachnoid hemorrhage (SAH). However, the benefit of early DC has not been shown yet. We aimed at identifying the clinical value of DC timing. Methods: We retrospectively analyzed 245 SAH patients who underwent DC between January 2003 and December 2015. The cohort was stratified into primary (at admission, n=171) and secondary DC (n=74). Moreover, primary DC was also subdivided into early (≤24 hours after ictus, n=120) and delayed (n=51) primary DC. Results: There was no difference between primary and secondary DC (65.5% and 74.3% respectively, p=0.1828) with regard to unfavorable outcome at 6 months post-SAH (defined as modified Rankin scale>3). However, individuals with early primary DC presented with significantly better functional outcome than the remaining cohort (p=0.014, OR=2.02) and even compared to the subgroup with delayed primary DC (p=0.023, OR=2.42). Among individuals with World Federation of Neurosurgical Societies Grade <5 at admission, the benefits of early DC were more impressive: lower rates of unfavorable outcome (p=0.003, OR=0.28), in-hospital mortality (p=0.031, OR=0.37) and cerebral infarctions (p=0.028, OR=0.38) on the follow-up computed tomography scans. Conclusion: Not the timing of DC indication (primary/secondary), but rather the actual time left between the ictus and DC is crucial for the functional improvement of SAH patients requiring DC. Especially, individuals without the signs of severe early brain injury strongly benefit from early DC.
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The impact of age on the incidence of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is a matter of ongoing discussion. The aim of this study was to identify age groups with a higher risk for developing vasospasm, delayed ischemic neurological deficit (DIND), or delayed infarction (DI) and to identify a cut-off age for a better risk stratification. We defined six age groups (<30, 30-39, 40-49, 50-59, 60-69, and >70 years). ROC analysis was performed to determine a cutoff age with the highest positive predictive value (PPV) for developing vasospasm, defined as a blood-flow-velocity-increase >120 cm/s in transcranial-Doppler-sonography (TCD). Multivariate binary-logistic-regression-analysis was then performed to evaluate differences in the incidence of cerebral vasospasm, DIND, and DI among the different age groups. A total of 753 patients were included in the study. The highest incidence (70 %) of TCD-vasospasm was found in patients between 30 and 39 years of age. The cutoff age with the highest PPV (65 %) for developing TCD-vasospasm was 38 years. Multivariate analysis revealed that age <38 years (OR 3.6; CI 95 % 2.1-6.1; p < 0.001) best predicted vasospasm, followed by the need for cerebrospinal fluid drainage (OR 1.5; CI 95 % 1.0-2.3; p = 0.04). However, lower age did not correlate with higher rates of DIND or infarcts. The overall vasospasm-incidence after aSAH is age-dependent and highest in the age group <38 years. Surprisingly, the higher incidence in the younger age group does not translate into a higher rate of DIND/DI. This finding may hint towards age-related biological factors influencing the association between arterial narrowing and cerebral ischemia.
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The elderly patients with aneurysmal subarachnoid hemorrhage (aSAH) have a greater risk of poor clinical outcome after endovascular treatment (EVT) than younger patients do. Hence, it is necessary to explore which factors are associated with poor outcome and develop a predictive score specifically for elderly patients with aSAH receiving EVT. The aim of this study was to develop and validate a predictive score for 1-year outcomes in individual elderly patients with aSAH underwent EVT. In this 10-year prospective study, 520 consecutive aSAH elderly (age ≥ 60 years) patients underwent EVT in a single center were included. The risk factors, periprocedural, and 1-year follow-up data of all patients were entered in a specific prospective database. The modified Rankin scale was used for evaluating clinical outcome. To optimize the model's predictive capacity, the original matrix was randomly divided in 2 submatrices (learning and testing). The predictive score was developed using Arabic numerals for all variables based on the variable coefficients (β) of multivariable logistic regression analysis in the learning set and the predictive performance evaluation was assessed in the testing set. The risk classes were constructed using classification criteria based on sensitivity and specificity. The poor outcome rate at 1 year was 26.15%. Six risk factors, including age, hypertension, Hunt–Hess scale, Fisher scale, aneurysm location, and periprocedural complications, were independently associated with poor outcome and assembled the Changhai score. The discriminative power analysis with the area under the receiver operating characteristic curve (AUC) of the Changhai score was statistically significant (0.864, 0.824–0.904, P < 0.001). The sensitivity and specificity of the Changhai score were 82.07% and 78.06%, respectively. Our study indicated that age, hypertension, Hunt–Hess scale, Fisher scale, aneurysm location, and periprocedural complications were independent risk factors of poor outcome for elderly aSAH patients underwent EVT. In combination with these risk factors, the Changhai score can be a useful tool in the prediction of clinical outcome but needs to be validated in various centers before it can be recommended for application.
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Cerebral vasospasm (CVS) is a frequent and serious neurosurgical complication, without sufficient therapy. This retrospective study was performed to analyze if nimodipine can improve prognosis and reduces ischemia secondary to delayed CVS after intracranial tumor surgery. A retrospective review was performed over the years 2011 to 2012 for patients with an anterior cranial fossa tumor and underwent intracranial tumor surgery. And the surgical field was soaked with nimodipine solution or normal saline. Transcranial Doppler ultrasonography was used to measure velocity in the middle cerebral artery (MCA) and the distal extracranial internal carotid artery (eICA). Follow-up was performed using the Glasgow Outcome Scale (GOS) after discharge. 94 patients that met the inclusion criteria. They included 50 males and 44 females, with a mean age of 49.6 yr. In the nimodipine group, CVS occurred in 13 patients; 9 patients had CVS between 4 and 7 days, and 4 had CVS between 8 and 14 days. In the normal saline group, 19 patients had CVS, 3 presented with CVS within 3 days, 11 between 4-7 days and 5 between 8-14 days. A significant difference in the occurrence of CVS was observed between the two groups. Preoperative and postoperative the MCA velocities were compared, revealing a significant change in the normal saline group but not in the nimodipine group. Nimodipine markedly improves prognosis and significantly reduces ischemia secondary to delayed CVS after intracranial tumor surgery, as well as the risks of mortality and morbidity.
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The intracerebral hemorrhage (ICH) score is a simple grading scale that can be used to stratify risk of 30 day mortality in ICH patients. A similar risk stratification scale for subarachnoid hemorrhage (SAH) is lacking. We sought to develop a risk stratification mortality score for SAH. With approval from the Institutional Review Board, we retrospectively reviewed 400 consecutive SAH patients admitted to our institution from August 1, 2006 to March 1, 2011. The SAH score was developed from a multivariable logistic regression model which was validated with bootstrap method. A separate cohort of 302 SAH patients was used for evaluation of the score. Among 400 patients with SAH, the mean age was 56.9 ± 13.9 years (range, 21.5-96.2). Among the 366 patients with known causes of SAH, 292 (79.8 %) of patients had aneurysmal SAH, 65 (17.8 %) were angiogram negative, and 9 (2 %) were other vascular causes. The overall in-hospital mortality rate was 20 %. In multivariable analysis, the variables independently associated with the in-hospital mortality were Hunt and Hess score (HH) (p < 0.0001), age (p < 0.0001), intraventricular hemorrhage (IVH) (p = 0.049), and re-bleed (p = 0.01). The SAH score (0-8) was made by adding the following points: HH (HH1-3 = 0, HH4 = 1, HH5 = 4), age (<60 = 0, 60-80 = 1, ≥80 = 2), IVH (no = 0, yes = 1), and re-bleed within 24 h (no = 0, yes = 1). Using our model, the in-hospital mortality rates for patients with score of 0, 1, 2, 3, 4, 5, 6, and 7 were 0.9, 4.5, 9.1, 34.5, 52.9, 60, 82.1, and 83.3 % respectively. Validation analysis indicates good predictive performance of this model. The SAH score allows a practical method of risk stratification of the in-hospital mortality. The in-hospital mortality increases with increasing SAH mortality score. Further investigation is warranted to validate these findings.
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Background and purpose: Although multiple intracranial aneurysms are frequent, determining treatment strategy and methods for them is often complicated. The aim of this study was to evaluate the safety and effectiveness of 1-stage coiling for multiple intracranial aneurysms. Materials and methods: All patients who underwent 1-stage coiling for ≥2 aneurysms were identified from a prospectively registered neurointerventional data base during 10 years. The patient characteristics and clinical and angiographic outcomes at discharge and follow-up were retrospectively evaluated. Results: One hundred sixty-seven patients (male/female ratio, 30:137; mean age, 58 years) with multiple aneurysms (418 aneurysms; mean, 2.5 aneurysms/patient) underwent attempted 1-stage coiling for ≥2 aneurysms (359 aneurysms; mean, 2.1 aneurysms/patient). In 131 patients (78.4%), all detected aneurysms were treated with coiling only. Treatment-related morbidity and mortality at discharge were 1.8% and 0.6% per patient, respectively. Of the 132 patients without subarachnoid hemorrhage, 129 (97.7%) had favorable outcomes (mRS 0-2) at discharge; of the 35 patients with SAH, 27 (77.1%) had favorable outcomes at discharge. Of the 162 patients (97%) for whom clinical follow-up was available (mean, 35.8 months), 154 patients (95.1%) had favorable outcomes. Immediate posttreatment angiography showed complete occlusion in 186 (51.8%) aneurysms, neck remnants in 134 (37.3%), sac remnants in 33 (9.2%), and failure in 6 (1.7%). Of the 262 (73.9%) aneurysms that underwent follow-up imaging (mean, 24.8 months), 244 (93.1%) showed a stable or improved state, with 12 (4.6%) minor and 6 (2.3%) major recurrences. Conclusions: One-stage coiling of multiple aneurysms seems to be safe and effective, with low morbidity and mortality.
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Recovery is common after subarachnoid hemorrhage (SAH), even in patients who are severely disabled at hospital discharge. Little is known about predictors of late recovery in such patients, even though such knowledge may influence treatment decisions. We hypothesized that cerebral infarction volume would be associated with 3 months outcomes in patients who are severely disabled at 14 days. We prospectively identified consecutive aneurysmal SAH patients, documented the development of cerebral infarction, and ascertained the modified Rankin Scale (mRS) at 14 days and 3 months. We included patients with mRS 4 or 5 and NIH Stroke Scale (NIHSS) at least 8 on hospital day 14 (i.e., severe neurologic impairment) and calculated infarct volume in a semi-automated fashion using CT imaging. We explored outcome determinants with ordinal regression. At 14 days, 66 patients were severely disabled, 65 (98.5 %) of whom had mRS of 5; the median NIHSS was 21 [14-24]. At 3 months, 20 (32.8 %) of the 61 patients with known outcomes were independent. Larger infarction volumes were associated with death (20.4 vs. 0.85 mL, P = 0.02). In ordinal regression, increased infarct volume was associated with the worse mRS after correction for WFNS grade, age, and withdrawal of life support (OR 1.01 per mL of infarct, 95 % CI 1.01-1.03, P = 0.01). After SAH, even with severe neurological injury at 14 days, good recovery is frequent and is associated with lower infarction volume. These data may help clinicians inform surrogate decision makers as they plan the future care of such severely disabled patients.
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Background: Cerebral vasospasm is one of the leading causes of poor outcome after aneurysmal subarachnoid hemorrhage. The risk factors for the development of vasospasm have been evaluated in many clinical studies. However, it remains unclear if vasospasm severity can be predicted. The purpose of this study was to determine if different demographic and clinical factors that appear to be predictors of vasospasm can also prognosticate the severity of cerebral vasospasm. Methods: We retrospectively analyzed consecutive patients with subarachnoid hemorrhage who underwent endovascular vasospasm treatment in a single center. In order to define predictors of vasospasm severity, we studied the demographic and clinical characteristics of these patients. Vasospasm severity was defined by cerebral angiography, transcranial Doppler ultrasound, and therapeutic response on endovascular treatment. Statistical analyses were performed to determine significant predictors. Results: A total of 70 patients with vasospasm were included. Early onset of mean flow velocities>160 cm/second on transcranial Doppler ultrasound correlated with severity of angiographic vasospasm (P=.0469) and resistance against intra-arterial papaverine (P=.0277). Younger age (<51 years of age) was significantly associated with severity of vasospasm regarding extension on angiography (P=.0422), the need for repetitive endovascular treatment (P=.0084), persistence of transcranial Doppler ultrasound vasospasm after endovascular treatment (P=.0004), and resistance against intra-arterial papaverine (P=.0341). Conclusions: Younger age and early onset of vasospasm on transcranial Doppler ultrasound are important predictors for vasospasm severity. We recommend early and aggressive therapy in this subgroup.
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Despite improvements in the clinical management of aneurysmal subarachnoid haemorrhage over the last decade, delayed cerebral ischaemia (DCI) remains the single most important cause of morbidity and mortality in those patients who survive the initial bleed. The pathological mechanisms underlying DCI are still unclear and the calcium channel blocker nimodipine remains the only therapeutic intervention proven to improve functional outcomes after SAH. The recent failure of the drug clazosentan to improve functional outcomes despite reducing vasoconstriction has moved the focus of research into DCI away from cerebral artery constriction towards a more multifactorial aetiology. Novel pathological mechanisms have been suggested, including damage to cerebral tissue in the first 72 h after aneurysm rupture ('early brain injury'), cortical spreading depression, and microthrombosis. A greater understanding of the significance of these pathophysiological mechanisms and potential genetic risk factors is required, if new approaches to the prophylaxis, diagnosis, and treatment of DCI are to be developed. Furthermore, objective and reliable biomarkers are needed for the diagnosis of DCI in poor grade SAH patients requiring sedation and to assess the efficacy of new therapeutic interventions. The purpose of this article is to appraise these recent advances in research into DCI, relate them to current clinical practice, and suggest potential novel avenues for future research.
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Aneurysmal subarachnoid haemorrhage (SAH) is a severe disease with high case-fatality and morbidity rates. After SAH, the value of C-reactive protein (CRP)-an acute phase sensitive inflammatory marker-as a prognostic factor has been poorly studied, with conflicting results. In this prospective study, we tested whether increased CRP levels increase independently the risk for cerebral infarct and poor outcome. Previous diseases as well as clinical, laboratory and radiological variables were recorded for 178 patients with SAH admitted within 48 h and with aneurysms occluded within 60 h after bleeding. Plasma CRP was measured, as well as computed tomography (CT) scans routinely obtained on admission, in the morning after aneurysm occlusion, and at discharge during second week after SAH. Factors predicting occurrence of cerebral infarct and poor outcome at 3 months after SAH were tested with multiple logistic regression. CRP levels increased significantly (p < 0.001) between hospital admission (mean ± SD, 11.4 ± 21.3 mg/l) and the postoperative morning (27.0 ± 31.0 mg/l) and then decreased (p < 0.001) during the the second week (19.8 ± 25.0 mg/l). Admission (18.0 ± 35.7 vs 8.5 ± 8.4 mg/l) and postoperative (41.0 ± 40.2 vs 21.1 ± 24.1 mg/l) CRP levels were higher (p < 0.001) in those with a poor outcome than in those with a favourable outcome, but CRP values did not predict delayed cerebral ischaemia or cerebral infarction. CRP levels did not independently predict outcome, since these correlated with admission clinical grade and occurrence of intraventricular haemorrhage. Higher increase in CRP level between admission and postoperative morning, however, independently predicted poor outcome (p = 0.004). Part of this increased risk was likely due to an appearance of early postoperative cerebral infarction. CRP levels correlate with outcome but do not seem to predict delayed cerebral ischaemia or infarction after SAH.
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After aneurysmal subarachnoid haemorrhage, severity of bleeding, and occurrence of rebleeding and cerebral infarcts are the main factors predicting outcome. We investigated predictive risk factors for both early and late cerebral infarcts, and whether time of appearance of infarct is associated with outcome. Previous diseases as well as clinical, laboratory and radiological variables including serial CT scans were recorded for 173 patients admitted within 48 h after bleeding and with ruptured aneurysm occlusion by open surgery within 60 h. Factors predicting occurrence of cerebral infarct and poor outcome at 3 months according to the Glasgow Outcome Scale were tested using multiple logistic regression. Of several potential predictors, poor outcome was independently predicted by patient age, rebleeding, intraventricular haemorrhage, intracerebral haematoma, delayed cerebral ischaemia with fixed symptoms and early new ischaemic lesion on CT scan appearing on the 1st post-operative morning (P<0.01 for each factor). After adjustment for confounding factors, occurrence of early infarct (odds ratio 12.5; 95% confidence interval 3.2-48.7; P<0.01), both early and late infarct (6.6; 1.1-40.4; P<0.05), and late infarct only (2.4; 0.6-9.1) increased risk for poor outcome. Adjusted independent significant risk factors for early infarction were duration of artery occlusion during surgery (1.4/min; 1.1-1.7, P<0.01) and admission plasma glucose level (1.3 per mM; 1.0-1.6, P<0.05) and for late infarction amount of subarachnoid blood (4.5; 1.3-14.9, P<0.05). Early infarction after surgical aneurysm occlusion seems to have different risk factors and worse prognosis than late infarct which is mostly associated with delayed cerebral ischaemia.
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Despite an undisputed association between vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH), there is debate if this association implies causality. It has been suggested that cerebral infarction is a better outcome measure than vasospasm in clinical trials and observational studies. To further investigate the relationship between infarction and outcome, we performed a systematic review and meta-analysis of all randomized, double-blind, placebo-controlled trials that studied the efficacy of pharmaceutical preventive strategies in SAH patients, and had both cerebral infarction and clinical outcome as outcome events. Effect sizes were expressed in (pooled) risk ratio (RR) estimates with corresponding 95% confidence intervals (CIs). Sensitivity analyses were performed for studies with a low risk of bias and for those who reported outcome at 3 months after SAH. Twenty-four studies including 8,552 patients were included. Pharmaceutical treatments decreased the incidence of both cerebral infarction (RR: 0.83; 95% CI: 0.74 to 0.93) and of poor functional outcome (RR: 0.92; 95% CI: 0.86 to 0.98). The sensitivity analyses did not change the results essentially. These data suggest that the previously observed association between cerebral infarction and functional outcome implies causality, and that cerebral infarction is a better outcome measure than vasospasm in clinical trials and observational studies.
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The goals of this study were to identify predictors of delayed cerebral infarction in aneurysmal SAH after intra-arterial (IA) vasodilator infusion and to select proper parameters for treatment success. Forty-three patients qualified for review. Cerebral infarction was determined by DWI within 1 week of angiographic vasospasm. Infarction developed in 18 of the 43 patients (41.9%) after IA vasodilator infusion and was associated with a high degree of proximal vessel residual narrowing and angiographic cerebral circulation time (CCT) prolongation at the end of IA vasodilator infusion (p < 0.001). A high degree of proximal residual narrowing (p = 0.018; odds ratio = 1.071; 95% confidence interval [CI] 1.012-1.123) and CCT prolongation at the end of the procedure (p = 0.007; odds ratio = 2.203; 95% CI 1.254-4.232) were found to be predictors of infarction by multivariate analysis. Furthermore, receiver operating characteristic (ROC) curves showed that both variables predicted the development of infarction (proximal vessel residual narrowing, area under the ROC curve [AUC], 0.828; CCT, AUC, 0.866). When proximal vessel narrowing of >30% or a CCT of >7 s by final angiography during IA vasodilator infusion were used as a threshold, the negative predictive value for infarction was 88.9% (95% CI 65.3-98.6%), and when narrowing was >30% and CCT was >7 s, the probability of subsequent cerebral infarction was 100% (95% CI 71.7-100%). Angiographic CCT and residual narrowing at the end of IA vasodilator infusion were found to predict the subsequent occurrence of cerebral infarction. The authors suggest that residual narrowing of 30% and a CCT of 7 s could be used as a minimum indicator of IA vasodilator infusion endpoints.
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The aim of this study was to test whether enoxaparin treatment (40 mg subcutaneously once daily) reduces the risk of cerebral infarction after subarachnoid hemorrhage (SAH) and to investigate predictive risk factors for permanent ischemic lesions visible on follow-up computerized tomography (CT) scans obtained 3 months after SAH. After undergoing surgery for a ruptured aneurysm, 170 patients were randomized in a prospective, double-blind, placebo-controlled trial to test the effect of enoxaparin on the occurrence of ischemic lesions, which were demonstrated on follow-up CT scans available for 156 patients. The presence of lesions correlated highly with an impaired outcome, as assessed using both the Glasgow Outcome and modified Rankin Scales (p < 0.01). Lesions occurred in 101 (65%) of the 156 patients. In half of the patients (51 patients) no lesion was visible on the CT scan obtained on the 1st postoperative day in 51 patients. On univariate analysis, the presence of lesions at 3 months post-SAH was not associated with enoxaparin treatment but did correlate with several clinical, radiological, and prehemorrhage variables. Significant independent risk factors for lesions consisted of an impaired initial clinical condition (odds ratio [OR] 2.63, 95% confidence interval [CI] 1.03-6.73), amount of subarachnoid blood (OR 6.51, 95% CI 2.27-18.65), nocturnal occurrence of SAH (that is, between 12:01 a.m. and 8:00 a.m.; OR 4.32, 95% CI 1.28-14.52), fixed symptoms of delayed ischemia (OR 5.21, 95% CI 1.02-26.49), duration of temporary artery occlusion during surgery (OR 1.66 per minute, 95% CI 1.20-2.31), and body mass index (OR 1.13/kg/m2, 95% CI 1.01-1.28). The presence of ischemic lesions can be predicted by the severity of bleeding, delayed cerebral ischemia, excess weight, duration of temporary artery occlusion, and occurrence of nocturnal aneurysm rupture.
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Cerebral infarction after aneurysmal subarachnoid haemorrhage (SAH) is presumed to be due to cerebral vasospasm, defined as arterial lumen narrowing from days 3 to 14. We reviewed the computed tomography scans of 103 patients with aneurysmal SAH for radiographic cerebral infarction and controlled for other predictors of outcome. A blinded neuroradiologist reviewed the angiograms. Cerebral infarction from vasospasm was judged to be unlikely if it was visible on computed tomography within 2 calendar days of SAH or if angiography showed no vasospasm in a referable vessel, or both. Cerebral infarction occurred in 29 (28%) of 103 patients with SAH. 18 patients had cerebral infarction that was unlikely to be due to vasospasm because it was visible on computed tomography by day 2 (6 (33%)) or because angiography showed no vasospasm in a referable artery (7 (39%)), or both (5 (28%)). In a multivariate model, cerebral infarction was significantly related to World Federation of Neurologic Surgeons grade (odds ratio (OR) 1.5/grade, 95% confidence interval (CI) 1.1 to 2.01, p = 0.006) and SAH-Physiologic Derangement Score (PDS) >2 (OR 3.7, 95% CI 1.4 to 9.8, p = 0.01) on admission. Global cerebral oedema (OR 4.3, 95% CI 1.5 to 12.5, p = 0.007) predicted cerebral infarction. Patients with cerebral infarction detectable by day 2 had a higher SAH-PDS than patients with later cerebral infarction (p = 0.025). Many cerebral infarctions after SAH are unlikely to be caused by vasospasm because they occur too soon after SAH or because angiography shows no vasospasm in a referable artery, or both. Physiological derangement and cerebral oedema may be worthwhile targets for intervention to decrease the occurrence and clinical impact of cerebral infarction after SAH.
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Identifying ischemic lesions after subarachnoid hemorrhage (SAH) is important because the appearance of these lesions on follow-up imaging correlates with a poor outcome. The effect of ischemic lesions seen on computed tomography (CT) scans during the first days of treatment remains unknown, however. In 156 patients with SAH, clinical course and outcome, as well as the appearance of ischemic lesions on serial CT scans, were prospectively monitored for 3 months. At 3 months after SAH, magnetic resonance imaging was performed to detect permanent lesions that had not been visible on CT. Of the 53 patients with no lesions on any of the follow-up CT scans, four (8%) had a poor outcome. Of the 52 patients with a new hypodense lesion on the first postoperative day CT, 23 (44%) had a poor outcome. Among the remaining 51 patients with a lesion appearing later than the first postoperative morning, 10 (20%) had a poor outcome (p < 0.001). After adjusting for patient age; clinical condition on admission; amounts of subarachnoid, intracerebral, and intraventricular blood; and plasma glucose and D-dimer levels, a hypodense lesion on CT on the first postoperative morning was an independent predictor of poor outcome after SAH (odds ratio 7.27, 95% confidence interval 1.54-34.37, p < 0.05). A new hypodense lesion on early postoperative CT seems to be an independent risk factor for poor outcome after SAH, and this early lesion development may be more detrimental to clinical outcome than a later lesion occurrence.
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Cerebral infarction is a frequent and serious complication of aneurysmal subarachnoid hemorrhage (SAH). This study aimed to identify independent predictors of the timing of cerebral infarction and clarify its impact on disease course and patients' outcome. All consecutive patients with SAH admitted to our institution from January 2005 to December 2012 were analyzed. Serial computed tomography (CT) scans were evaluated for cerebral infarctions. Demographic, clinical, laboratory and radiological data of patients during hospitalization as well as clinical follow-ups 6 months after SAH were recorded. Of the 632 analyzed patients, 320 (51%) developed cerebral infarction on CT scans. 136 patients (21.5%) with early cerebral infarction (occurring within 3 days after SAH) had a significantly higher risk of unfavorable outcome than patients with late infarction [odds ratio (OR) 2.94; P = 0.008], a higher in-hospital mortality (OR 3.14; P = 0.0002) and poorer clinical outcome after 6 months (OR 0.54; P < 0.0001). The rates of decompressive craniectomy (OR 1.96, P = 0.0265), tracheostomy (OR 1.87, P = 0.0446), the duration of intensive care unit stay and mechanical ventilation were significantly higher in patients with early infarction. In multivariate analysis, Hunt and Hess grades 4 and 5 (OR 2.06, P = 0.008), Fisher grades 3 and 4 (OR 3.99, P = 0.014), sustained elevations of intracranial pressure >20 mmHg (OR 5.95, P < 0.0001) and early vasospasm on diagnostic angiograms (OR 3.01, P = 0.008) were predictors of early cerebral infarction. Early cerebral infarction after SAH is associated with severe clinical course and unfavorable outcome and can be reliably predicted by poor initial clinical condition, thick subarachnoid clot, early angiographic vasospasm and sustained elevations of intracranial pressure. © 2015 EAN.
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Introduction CT-angiography gains an increasing role in the initial diagnosis of patients with nontraumatic subarachnoid hemorrhage (SAH). However, the implementation of CT-angiography does not always exclude the necessity of conventional angiography. Our objective was to determine the practical utility and cost-effectiveness of CT-angiography. Methods All patients with nontraumatic subarachnoid hemorrhage admitted to our university hospital after implementation of CT-angiography between June 1, 2011 and June 30, 2012 were retrospectively analyzed in regard to factors of treatment flow, radiation exposure, harms of contrast medium loading, and diagnostic costs. A control group of the same size was assembled from previously admitted SAH patients, who did not undergo pretreatment CT-angiography. Furthermore, cost-effectiveness analysis was performed. Results The final analysis consisted of 93 patients in each group. Of 93 patients with pretreatment CT-angiography, 74 had to undergo conventional angiography for diagnostic and/or therapeutic purposes. CT-angiography had significant impact on the reduction of collective effective radiation dose by 4.419 mSv per person (p = 0.0002) and was not associated with additional harms. Despite the significantly earlier detection of aneurysms with CT-angiography (p
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Background: Delayed cerebral ischemia is common after aneurysmal subarachnoid hemorrhage (aSAH) and is a major contributor to poor outcome. Yet, although generally attributed to arterial vasospasm, neurological deterioration may also occur in the absence of vasospasm. Objective: To determine the relationship between delayed infarction and angiographic vasospasm and compare the characteristics of infarcts related to vasospasm vs those unrelated. Methods: A retrospective review of patients with aSAH admitted from July 2007 through June 2011. Patients were included if they were admitted within 48 hours of SAH, had a computed tomography scan both 24 to 48 hours following aneurysm treatment and ≥7 days after SAH, and had a catheter angiogram to evaluate for vasospasm. Delayed infarcts seen on late computed tomography but not postprocedurally were attributed to vasospasm if there was moderate or severe vasospasm in the corresponding vascular territory on angiography. Infarct volume was measured by perimeter tracing. Results: Of 276 aSAH survivors, 134 had all imaging requisite for inclusion. Fifty-four (34%) had moderate or severe vasospasm, of whom 17 (31%) had delayed infarcts, compared with only 3 (4%) of 80 patients without vasospasm (P < .001). There were a total of 29 delayed infarcts in these 20 patients; 21 were in a territory with angiographic vasospasm, but 8 (28%) were not. Infarct volume did not differ between vasospasm-related (18 ± 25 mL) and vasospasm-unrelated (11 ± 12 mL) infarcts (P = .54), but infarcts in the absence of vasospasm were more likely watershed (50% vs. 10%, P = .03). Conclusion: Delayed infarcts following aSAH can occur in territories without angiographic vasospasm and are more likely watershed in distribution.
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OBJECTIVE: A small number of patients with aneurysmal subarachnoid hemorrhage have angiographic evidence of cerebral vasospasm within 48 hours of the onset of hemorrhage. The present study analyzes the prognostic value and determinants of this ultraearly angiographic finding. METHODS: We analyzed prospectively collected data from the placebo-treated group in a multicenter clinical trial conducted at 54 neurosurgical centers in North America. The presence and severity of ultraearly angiographic vasospasm (UEAV) was determined by a blinded review of the admission angiograms. Using logistic regression analysis, we identified independent determinants of UEAV from demographic, clinical, laboratory, and neuroimaging characteristics of the patients. The impact of UEAV on the risk of symptomatic vasospasm and 3-month outcome was analyzed after adjusting for potential confounding factors. RESULTS: Of 296 patients in the analysis, 37 (13%) had angiographic evidence of vasospasm at admission. An initial Glasgow Coma Scale score of less than 14 (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.1-6.0), and serum sodium greater than 138 mmol/L (OR, 3.4; 95% CI, 1.5-8.3) were associated with UEAV. UEAV was associated with increased risk of symptomatic vasospasm (OR, 2.5; 95% CI, 1.2-5.4) and poor outcome at 3 months (OR, 2.8; 95% CI, 1.2-6.3), after adjusting for other variables. This risk of symptomatic vasospasm was not influenced by early surgery (within 48 h of hemorrhage onset). Poor outcome was more likely to occur in patients with UEAV who did not undergo early surgery (P = 0.03). CONCLUSION: Our analysis suggests that patients with angiographic evidence of vasospasm at admission are at high risk for both symptomatic vasospasm and poor outcome. We also found that early surgery did not aggravate this risk.
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Prediction models are increasingly used to complement clinical reasoning and decision making in modern medicine in general, and in the cardiovascular domain in particular. Developed models first and foremost need to provide accurate and (internally and externally) validated estimates of probabilities of specific health conditions or outcomes in targeted patients. The adoption of such models must guide physician's decision making and an individual's behaviour, and consequently improve individual outcomes and the cost-effectiveness of care. In a series of two articles we review the consecutive steps generally advocated for risk prediction model research. This first article focuses on the different aspects of model development studies, from design to reporting, how to estimate a model's predictive performance and the potential optimism in these estimates using internal validation techniques, and how to quantify the added or incremental value of new predictors or biomarkers (of whatever type) to existing predictors. Each step is illustrated with empirical examples from the cardiovascular field.
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Despite advances in aneurysm ablation and the initial management of patients presenting with aneurysmal subarachnoid hemorrhage, delayed cerebral ischemia remains a significant source of morbidity. Traditionally, delayed cerebral ischemia was thought to be a result of vasospasm of the proximal intracranial vessels, and clinical trials have relied largely on radiographic evidence of vasospasm as a surrogate for functional outcome. However, a number of trials have demonstrated a dissociation between angiographic vasospasm and outcome, and more recent data suggest that other mechanisms of injury, such as microvascular dysfunction and complex neuronal-glial interactions, may influence the development of delayed ischemic deficit after aneurysmal subarachnoid hemorrhage. Our evolving understanding of the pathophysiology of delayed cerebral ischemia may offer the opportunity to test new therapeutic strategies in this area and improve clinical trial design.
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The long-standing concept that delayed cerebral infarction after aneurysmal subarachnoid hemorrhage results exclusively from large artery vasospasm recently has been challenged. We used data from the CONSCIOUS-1 trial to determine the relationship between angiographic vasospasm and cerebral infarction after subarachnoid hemorrhage. We performed a post hoc exploratory analysis of the CONSCIOUS-1 data. All patients underwent catheter angiography before treatment and 9±2 days after subarachnoid hemorrhage. CT was performed before and after aneurysm treatment, and 6 weeks after subarachnoid hemorrhage. Angiograms and CT scans were assessed by centralized blinded review. Angiographic vasospasm was classified as none/mild (0%-33% decrease in arterial diameter), moderate (34%-66%), or severe (≥67%). Infarctions were categorized as secondary to angiographic vasospasm, other, or unknown causes. Logistic regression was conducted to determine factors associated with infarction. Complete data were available for 381 of 413 patients (92%). Angiographic vasospasm was none/mild in 209 (55%) patients, moderate in 118 (31%), and severe in 54 (14%). Infarcts developed in 6 (3%) of 209 with no/mild, 12 (10%) of 118 patients with moderate, and 25 (46%) of 54 patients with severe vasospasm. Multivariate analysis found a strong association between angiographic vasospasm and cerebral infarction (OR, 9.3; 95% CI, 3.7-23.4). The significant association persisted after adjusting for admission neurological grade and aneurysm size. Method of aneurysm treatment was not associated with a significant difference in frequency of infarction. A strong association exists between angiographic vasospasm and cerebral infarction. Efforts directed at further reducing angiographic vasospasm are warranted.
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As many as 33% of patients suffering from subarachnoid hemorrhage (SAH) present with multiple intracranial aneurysms (MIAs). It is believed that aneurysm surgery has the potential to increase the risk of cerebral vasospasm due to surgical manipulations of the parent vessels and brain tissue. Consequently, 1-stage surgery of MIAs, which usually takes longer and requires more manipulation, could even further increase the risk of vasospasm. The aim of this study is to define the correlation between vasospasm and the operative treatment of single intracranial aneurysms versus MIAs in a 1-stage operation. The authors analyzed a database including 1016 patients with SAH, identified retrospectively between 1989 and 1996 and prospectively collected between 1997 and 2004. Exclusion criteria were endovascular treatment, surgery after SAH Day 3, and, in patients with MIAs, undergoing more than 1 operation. Cerebral vasospasm was diagnosed by transcranial Doppler (TCD) ultrasonography and was defined as a maximum mean blood flow velocity > 120 cm/second. The diagnosis of symptomatic vasospasm was made if a new neurological deficit occurred that could not be explained by concomitant complications. A total of 643 patients who experienced 810 aneurysms were included. Four hundred twenty-four patients were female (65.9%) and 219 were male (34.1%) with an average age of 53.1 years. One hundred twenty-one patients (18.8%) were diagnosed with MIAs. Maximum mean flow velocities measured by TCD were 131 cm/second in patients with MIAs and 129.5 cm/second in patients with single intracranial aneurysms. The incidence of TCD vasospasm (p = 0.561) as well as of symptomatic vasospasm (p = 0.241) was not significantly different in the 2 groups. Clipping of more than 1 aneurysm in a 1-stage operation within 72 hours after SAH can be performed without increasing the risk of cerebral (TCD) vasospasm and symptomatic vasospasm.
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Vasospasm is a major complication of aneurysmal subarachnoid hemorrhage (SAH) and affects clinical outcome. The ability to predict cerebral vasospasm after SAH would allow the neuro-intensivist to institute preemptive and more aggressive therapy. Social, clinical, and radiological information on adult SAH patients recently admitted to our hospital were reviewed. Univariate and multivariate statistical methods were used to examine the impact of patient demographics, clinical variables, and radiologic characteristics on the development of angiographic vasospasm. One hundred and sixty three patients were identified (102 females, 63%). A total of 34 patients (21%) developed angiographic vasospasm. In univariate analysis, occurrence of cerebral vasospasm was associated with poor World Federation of Neurological Surgeons (WFNS 4-5, P = 0.003) and modified Fisher (MFS 3-4, P = 0.02) grades, elevated Hijdra sum score (HSS > or =23, P = 0.0001), female gender (P = 0.04), development of hydrocephalus (P = 0.01), and a history of tobacco use (P = 0.02). In multivariable analysis, only the HSS > or =23 (P = 0.01) and history of smoking (P = 0.02) predicted cerebral vasospasm. Combined history of smoking and HSS >23 had positive and negative predictive values of 37 and 88%, respectively, for prediction of cerebral vasospasm after aneurysmal hemorrhage. Hijdra sum score and a history of smoking are the strongest predictors of cerebral vasospasm on angiography. HSS is superior to the MFS as a radiologic grading tool to predict occurrence of angiographic vasospasm after aneurysmal subarachnoid hemorrhage.
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Cerebral infarction (CI) after subarachnoid hemorrhage (SAH) is well described, but there is no validated classification. We prospectively enrolled 119 consecutive patients with SAH. We recorded admission World Federation of Neurological Societies grade and Columbia computed tomographic scores. Vasospasm was defined as transcranial Doppler of greater than 120 cm/second or typical clinical symptoms. CI was defined by computed tomographic or magnetic resonance imaging scan, and the date of discovery was recorded. CI was classified by a previously published method (single versus multiple, cortical versus deep versus combined). Outcomes were assessed at 14 days or discharge with the National Institutes of Health Stroke Scale and modified Rankin Scale (mRS), and at 28 days and 3 months with the mRS. Vasospasm was associated with a higher risk of CI (odds ratio, 2.6; 95% confidence interval, 1.3-5.6; P = 0.01). The median time to detection was 4.2 days (interquartile range, 1.6-7.6 days) after SAH onset. CI classification was associated with the National Institutes of Health Stroke Scale score at 14 days (P = 0.002) and intensive care unit length of stay (P = 0.001). CI location (cortical, deep, or combined) was associated with National Institutes of Health Stroke Scale and mRS score at 14 days, and mRS score at 28 days and 3 months (P </= 0.02 for all). In a multiple logistic regression model, CI classification, World Federation of Neurological Societies grade, aneurysm diameter, and age were all associated with mRS score at 28 days and 3 months (P </= 0.05). Combined cortical and deep CI was associated with less improvement and poor outcome. CI classification predicts outcomes after SAH. Future reports of CI after SAH should include this or similar descriptive information.
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Influenza virus infections cause significant morbidity and often result in hospitalization in children. Many children with influenza seek care in emergency settings during seasonal influenza epidemics. We hypothesized that certain features could predict the need for hospitalization in children with influenza. Retrospective cohort study of all children 18 years or younger seen at a children's hospital with laboratory-confirmed influenza infection between July 2001 and June 2004. Medical records of children with confirmed influenza virus infection were reviewed. Predictors of admission were identified using logistic regression models. An influenza risk score system was created and validated based on 4 predictors. We identified 1230 children with laboratory proven influenza virus infection, 541 were hospitalized. Multivariate logistic regression demonstrated that 4 predictors were independently strongly associated with hospitalization. In the clinical prediction rule for children with influenza who were hospitalized, history of a high-risk medical condition (odds ratio [OR], 4.06; 95% confidence interval [CI], 2.91-5.68) was worth 2 points. Respiratory distress on physical examination (OR, 2.33; 95% CI, 1.61-3.38) was worth 1 point. Radiographic evidence of focal pneumonia (OR, 7.82; 95% CI, 3.62-16.92) was worth 3 points and influenza B infection (OR, 3.99; 95% CI, 2.57-6.21) was worth 2 points. High-risk children with influenza with a total risk score of 3 to 8 had an 86% probability of hospitalization. The presence of a high-risk medical condition, respiratory distress on physical examination, radiographic evidence of focal pneumonia, and influenza B infection were the 4 strongest predictors of hospitalization. The risk score assigned to a child with influenza may provide a disposition tool for predicting hospitalization in children in seasonal influenza epidemics.
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The authors sought to determine frequency, risk factors, and impact on outcome of asymptomatic cerebral infarction due to vasospasm after subarachnoid hemorrhage (SAH). The authors prospectively studied 580 patients with SAH admitted to their center between July 1996 and May 2002. Delayed cerebral ischemia (DCI) from vasospasm was defined as 1) a new focal neurological deficit or decrease in level of consciousness, 2) a new infarct revealed by follow-up CT imaging, or both, after excluding causes other than vasospasm. Outcome at 3 months was assessed using the modified Rankin Scale. Delayed cerebral ischemia occurred in 121 (21%) of 580 patients. Of those with DCI, 36% (44 patients) experienced neurological deterioration without a corresponding infarct, 42% (51 patients) developed an infarct in conjunction with neurological deterioration, and 21% (26 patients) had a new infarct on CT without concurrent neurological deterioration. In a multivariate analysis, risk factors for asymptomatic DCI included coma on admission, placement of an external ventricular drain, and smaller volumes of SAH (all p < or = 0.03). Patients with asymptomatic DCI were less likely to be treated with vasopressor agents than those with symptomatic DCI (64 vs 86%, p = 0.01). After adjusting for clinical grade, age, and aneurysm size, the authors found that there was a higher frequency of death or moderate-to-severe disability at 3 months (modified Rankin Scale Score 4-6) in patients with asymptomatic DCI than in patients with symptomatic DCI (73 vs 40%, adjusted odds ratio 3.9, 95% confidence interval 1.3-12.0, p = 0.017). Approximately 20% of episodes of DCI after SAH are characterized by cerebral infarction in the absence of clinical symptoms. Asymptomatic DCI is particularly common in comatose patients and is associated with poor outcome. Strategies directed at diagnosing and preventing asymptomatic infarction from vasospasm in patients with poor-grade SAH are needed.
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Delayed cerebral ischemia is a major cause of morbidity and death following aneurysmal subarachnoid hemorrhage and requires timely intervention for a successful outcome to be achieved. In this study the investigators compared the commonly used Fisher scale with 2 newer radiographic scales for the prediction of vasospasm, delayed infarction, and poor outcome. This was a single-center, retrospective cohort study involving 271 consecutive patients with a ruptured cerebral aneurysm. Without knowledge of subsequent events, admission CT scans were each assigned scores by using 3 different grading schemes: the Fisher, modified Fisher, and Claassen scales. For each of the scales, the relationship between an increasing score and the risk of later complications was assessed in univariate and multiple logistic regression analyses. With the Fisher scale, the risk of complications was relatively high when the score was 3, but not for other scores. In contrast, using the other scales, there was a more linear relationship between a rising score and the frequency of complications. This was particularly true for the modified Fisher scale, in which each stepwise increase was associated with an escalating risk of vasospasm, delayed infarction, and poor prognosis. Kappa scores measuring interobserver variability among 4 CT readers were also slightly better with the newer scales. Although the modified Fisher and Claassen scales have yet to be prospectively validated, the authors' findings suggest that the clinical performance of these systems is superior to that of the Fisher scale.
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Interobserver agreement for the assessment of handicap in stroke patients was investigated in a group of 10 senior neurologists and 24 residents from two centers. One hundred patients were separately interviewed by two physicians in different combinations. The degree of handicap was recorded by each observer on the modified Rankin scale, which has six grades (0-5). The agreement rates were corrected for chance (kappa statistics). Both physicians agreed on the degree of handicap in 65 patients; they differed by one grade in 32 patients and by two grades in 3 patients. Kappa for all pairwise observations was 0.56; the value for weighted kappa (with quadratic disagreement weights) was 0.91. Our results confirm the value of the modified Rankin scale in the assessment of handicap in stroke patients; nevertheless, further improvements are possible.
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Sixty-eight patients with intraventricular hemorrhage (IVH) diagnosed by computed tomography (CT) were reviewed retrospectively to determine the etiology and prognosis, relationship to delayed hydrocephalus, and effect on neurological outcome. The most common causes were a ruptured aneurysm, trauma, and hypertensive hemorrhage. Ruptured aneurysms of the anterior communicating artery can often be predicted from the nonenhanced CT scan. The total mortality rate was 50%; however, 21% of patients returned to normal or had only mild disability. Patients in whom no cause was identified had a better prognosis. Delayed hydrocephalus was related to the effects of subarachnoid hemorrhage rather than obstruction of the ventricular system by blood. IVH per se is seldom a major factor in the neurological outcome.
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In 47 cases of verified ruptured saccular aneurysm, we investigated the relationship of the amount and distribution of subarachnoid blood detected by computerized tomography to the later development of cerebral vasospasm. When the subarachnoid blood was not detected or was distributed diffusely, severe vasospasm was almost never encounters (1 of 18 cases). In the presence of subarachnoid blood clots larger than 5 X 3 mm (measured on the reproduced images) or layers of blood 1 mm or more thick in fissures and vertical cisterns, severe spasm followed almost invariably (23 of 24 cases). There was an almost exact correspondence between the site of the major subarachnoid blood clots and the location of severe vasospasm. Every patient with severe vasospasm manifested delayed symptoms and signs. Excellent correlation existed between the particular artery in vasospasm and the delayed clinical syndrome. Severe vasospasm involved the anterior cerebral artery in 20 cases and the middle cerebral artery in only 14. As the grading system used is partly subjective, the findings should be regarded as preliminary. The results, if confirmed, indicate that blood localized in the subarachnoid space in sufficient amount at specific sites is the only important etiological factor in vasospasm. It should be possible to identify patients in jeopardy from vasospasm and institute early preventive measures. (Neurosurgery, 6: 1--9, 1980)