scholarly journals APOE Genotype and Functional Outcome Following Aneurysmal Subarachnoid Hemorrhage

2008 ◽  
Vol 10 (3) ◽  
pp. 205-212 ◽  
Author(s):  
Matthew J. Gallek ◽  
Yvette P. Conley ◽  
Paula R. Sherwood ◽  
Michael B. Horowitz ◽  
Amin Kassam ◽  
...  

Apolipoprotein E (apoE), the major apolipoprotein in the central nervous system, has been shown to influence neurologic disease progression and response to neurologic injury in a gene-specific manner. Presence of the APOE4 allele is associated with poorer response to traumatic brain injury and ischemic stroke, but the association between APOE genotype and outcome following aneurysmal subarachnoid hemorrhage (SAH) remains unclear. The purpose of this project was to investigate the association between APOE genotype and outcome after SAH. We also explored the association of APOE4 genotype and cerebral vasospasm (CV) presence in a subsample of our population with available angiographic data. A sample of 206 aneurysmal SAH participants had APOE genotyping performed, Glasgow outcome scores (GOS) and modified Rankin scores (MRS) collected at 3 and 6 months after aneurysm rupture. No significant association was found between the presence of the APOE4 genotype and functional outcomes controlling for age, race, size of hemorrhage (Fisher grade), and severity of injury (Hunt & Hess grade). However when controlling for CV and the covariates listed above, individuals with the APOE4 allele had worse functional outcomes at both time points. The presence of the APOE2 allele was not associated with functional outcomes even when considering presence of CV. There was no difference in mortality associated with APOE4 presence, APOE2 presence, or presence of CV. These findings suggest APOE4 allele is associated with poor outcome after aneurysmal SAH.

2006 ◽  
Vol 105 (5) ◽  
pp. 723-729 ◽  
Author(s):  
Martina Stippler ◽  
Elizabeth Crago ◽  
Elad I. Levy ◽  
Mary E. Kerr ◽  
Howard Yonas ◽  
...  

Object Despite the application of current standard therapies, vasospasm continues to result in death or major disability in patients treated for ruptured aneurysms. The authors investigated the effectiveness of continous MgSO4 infusion for vasospasm prophylaxis. Methods Seventy-six adults (mean age 54.6 years; 71% women; 92% Caucasian) were included in this comparative matched-cohort study of patients with aneurysmal subarachnoid hemorrhage on the basis of computed tomography (CT) findings. Thirty-eight patients who received continuous MgSO4 infusion were matched for age, race, sex, treatment option, Fisher grade, and Hunt and Hess grade to 38 historical control individuals who did not receive MgSO4 infusion. Twelve grams of MgSO4 in 500 ml normal saline was given intravenously daily for 12 days if the patient presented within 48 hours of aneurysm rupture. Vasospasm was diagnosed on the basis of digital substraction angiography, CT angiography, and transcranial Doppler ultrasonography, and evidence of neurological deterioration. Symptomatic vasospasm was present at a significantly lower frequency in patients who received MgSO4 infusion (18%) compared with patients who did not receive MgSO4 (42%) (p = 0.025). There was no significant difference in mortality rate at discharge (p = 0.328). A trend toward improved outcome as measured by the modifed Rankin Scale (p = 0.084), but not the Glasgow Outcome Scale (p = 1.0), was seen in the MgSO4-treated group. Conclusions Analysis of the results suggests that MgSO4 infusion may have a role in cerebral vasospasm prophylaxis if therapy is initiated within 48 hours of aneurysm rupture.


2017 ◽  
Vol 20 (2) ◽  
pp. 177-182 ◽  
Author(s):  
Lacey Wright Heinsberg ◽  
Eleanor Turi ◽  
Dianxu Ren ◽  
Elizabeth Crago ◽  
Sheila Alexander ◽  
...  

Survivors of aneurysmal subarachnoid hemorrhage (aSAH) often experience unfavorable functional outcomes that result in a reduced ability to independently perform activities of daily living. The apolipoprotein E gene ( APOE) encodes for a protein known to facilitate lipid transport and aid in neuronal repair within the central nervous system and to moderate the inflammatory response, making functional variations in this gene likely candidate biomarkers to predict outcomes following aSAH. In the present work, we examined the relationship between APOE genotype and the ability to perform activities of daily living as measured by the Barthel Index (BI) score at 3 months ( n = 298) and 12 months ( n = 288) following aSAH. APOE genotypes were determined using polymerase chain reaction followed by restriction digestion and gel electrophoresis and treated as binary variables depending on the presence or absence of alleles E4 and E2. Multiple logistic regression was used to determine whether APOE genotype accounted for variability in BI score after controlling for age, sex, and severity of clinical condition as measured by the Hunt and Hess classification. No significant association was found between the presence of allele E4 and BI score at 3 ( p = .20) or 12 months ( p = .29) or between the presence of allele E2 and BI score at 3 ( p = .23) or 12 months ( p = .86) after controlling for covariates. The results of this study do not support a relationship between APOE genotype and the ability to perform activities of daily living after aSAH.


2021 ◽  
pp. 1-9
Author(s):  
Badih J. Daou ◽  
Siri Sahib S. Khalsa ◽  
Sharath Kumar Anand ◽  
Craig A. Williamson ◽  
Noah S. Cutler ◽  
...  

OBJECTIVEHydrocephalus and seizures greatly impact outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH); however, reliable tools to predict these outcomes are lacking. The authors used a volumetric quantitative analysis tool to evaluate the association of total aSAH volume with the outcomes of shunt-dependent hydrocephalus and seizures.METHODSTotal hemorrhage volume following aneurysm rupture was retrospectively analyzed on presentation CT imaging using a custom semiautomated computer program developed in MATLAB that employs intensity-based k-means clustering to automatically separate blood voxels from other tissues. Volume data were added to a prospectively maintained aSAH database. The association of hemorrhage volume with shunted hydrocephalus and seizures was evaluated through logistic regression analysis and the diagnostic accuracy through analysis of the area under the receiver operating characteristic curve (AUC).RESULTSThe study population comprised 288 consecutive patients with aSAH. The mean total hemorrhage volume was 74.9 ml. Thirty-eight patients (13.2%) developed seizures. The mean hemorrhage volume in patients who developed seizures was significantly higher than that in patients with no seizures (mean difference 17.3 ml, p = 0.01). In multivariate analysis, larger hemorrhage volume on initial CT scan and hemorrhage volume > 50 ml (OR 2.81, p = 0.047, 95% CI 1.03–7.80) were predictive of seizures. Forty-eight patients (17%) developed shunt-dependent hydrocephalus. The mean hemorrhage volume in patients who developed shunt-dependent hydrocephalus was significantly higher than that in patients who did not (mean difference 17.2 ml, p = 0.006). Larger hemorrhage volume and hemorrhage volume > 50 ml (OR 2.45, p = 0.03, 95% CI 1.08–5.54) were predictive of shunt-dependent hydrocephalus. Hemorrhage volume had adequate discrimination for the development of seizures (AUC 0.635) and shunted hydrocephalus (AUC 0.629).CONCLUSIONSHemorrhage volume is an independent predictor of seizures and shunt-dependent hydrocephalus in patients with aSAH. Further evaluation of aSAH quantitative volumetric analysis may complement existing scales used in clinical practice and assist in patient prognostication and management.


2011 ◽  
Vol 114 (4) ◽  
pp. 1045-1053 ◽  
Author(s):  
Kelly B. Mahaney ◽  
Michael M. Todd ◽  
James C. Torner

ObjectThe past 30 years have seen a shift in the timing of surgery for aneurysmal subarachnoid hemorrhage (SAH). Earlier practices of delayed surgery that were intended to avoid less favorable surgical conditions have been replaced by a trend toward early surgery to minimize the risks associated with rebleeding and vasospasm. Yet, a consensus as to the optimal timing of surgery has not been reached. The authors hypothesized that earlier surgery, performed using contemporary neurosurgical and neuroanesthesia techniques, would be associated with better outcomes when using contemporary management practices, and sought to define the optimal time interval between SAH and surgery.MethodsData collected as part of the Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) were analyzed to investigate the relationship between timing of surgery and outcome at 3 months post-SAH. The IHAST enrolled 1001 patients in 30 neurosurgical centers between February 2000 and April 2003. All patients had a radiographically confirmed SAH, were World Federation of Neurosurgical Societies Grades I–III at the time of surgery, and underwent surgical clipping of the presumed culprit aneurysm within 14 days of the date of hemorrhage. Patients were seen at 90-day follow-up visits. The primary outcome variable was a Glasgow Outcome Scale score of 1 (good outcome). Intergroup differences in baseline, intraoperative, and postoperative variables were compared using the Fisher exact tests. Variables reported as means were compared with ANOVA. Multiple logistic regression was used for multivariate analysis, adjusting for covariates. A p value of less than 0.05 was considered to be significant.ResultsPatients who underwent surgery on Days 1 or 2 (early) or Days 7–14 (late) (Day 0 = date of SAH) fared better than patients who underwent surgery on Days 3–6 (intermediate). Specifically, the worst outcomes were observed in patients who underwent surgery on Days 3 and 4. Patients who had hydrocephalus or Fisher Grade 3 or 4 on admission head CT scans had better outcomes with early surgery than with intermediate or late surgery.ConclusionsEarly surgery, in good-grade patients within 48 hours of SAH, is associated with better outcomes than surgery performed in the 3- to 6-day posthemorrhage interval. Surgical treatment for aneurysmal SAH may be more hazardous during the 3- to 6-day interval, but this should be weighed against the risk of rebleeding.


Neurosurgery ◽  
2015 ◽  
Vol 77 (5) ◽  
pp. 786-793 ◽  
Author(s):  
◽  
Carole L. Turner ◽  
Karol Budohoski ◽  
Christopher Smith ◽  
Peter J. Hutchinson ◽  
...  

Abstract BACKGROUND: There remains a proportion of patients with unfavorable outcomes after aneurysmal subarachnoid hemorrhage, of particular relevance in those who present with a good clinical grade. A forewarning of those at risk provides an opportunity towards more intensive monitoring, investigation, and prophylactic treatment prior to the clinical manifestation of advancing cerebral injury. OBJECTIVE: To assess whether biochemical markers sampled in the first days after the initial hemorrhage can predict poor outcome. METHODS: All patients recruited to the multicenter Simvastatin in Aneurysmal Hemorrhage Trial (STASH) were included. Baseline biochemical profiles were taken between time of ictus and day 4 post ictus. The t-test compared outcomes, and a backwards stepwise binary logistic regression was used to determine the factors providing independent prediction of an unfavorable outcome. RESULTS: Baseline biochemical data were obtained in approximately 91% of cases from 803 patients. On admission, 73% of patients were good grade (World Federation of Neurological Surgeons grades 1 or 2); however, 84% had a Fisher grade 3 or 4 on computed tomographic scan. For patients presenting with good grade on admission, higher levels of C-reactive protein, glucose, and white blood cells and lower levels of hematocrit, albumin, and hemoglobin were associated with poor outcome at discharge. C-reactive protein was found to be an independent predictor of outcome for patients presenting in good grade. CONCLUSION: Early recording of C-reactive protein may prove useful in detecting those good grade patients who are at greater risk of clinical deterioration and poor outcome.


2004 ◽  
Vol 101 (2) ◽  
pp. 255-261 ◽  
Author(s):  
Christopher Reilly ◽  
Chris Amidei ◽  
Jocelyn Tolentino ◽  
Babak S. Jahromi ◽  
R. Loch Macdonald

Object. This study was conducted for two purposes. The first was to determine whether a combination of measurements of subarachnoid clot volume, clearance rate, and density could improve prediction of which patients experience vasospasm. The second was to determine if each of these three measures could be used independently to predict vasospasm. Methods. Digital files of the cranial computerized tomography (CT) scans obtained in 75 consecutive patients admitted within 24 hours of subarachnoid hemorrhage (SAH) were analyzed in a blinded fashion by an observer who used quantitative imaging software to measure the volume of SAH and its density. Clot clearance rates were measured by quantifying SAH volume on subsequent CT scans. Vasospasm was defined as new onset of a focal neurological deficit or altered consciousness 5 to 12 days after SAH in the absence of other causes of deterioration, diagnosed with the aid of or exclusively by confirmatory transcranial Doppler ultrasonography and/or cerebral angiography. Univariate analysis showed that vasospasm was significantly associated with the SAH grade as classified on the Fisher scale, the initial clot volume, initial clot density, and percentage of clot cleared per day (p < 0.05). In multivariate analysis, initial clot volume and percentage of clot cleared per day were significant predictors of vasospasm (p < 0.05), whereas Fisher grade and initial clot density were not. Conclusions. Quantitative analysis of subarachnoid clot shows that vasospasm is best predicted by initial subarachnoid clot volume and the percentage of clot cleared per day.


2021 ◽  
pp. neurintsurg-2021-017424
Author(s):  
Joshua S Catapano ◽  
Visish M Srinivasan ◽  
Kavelin Rumalla ◽  
Mohamed A Labib ◽  
Candice L Nguyen ◽  
...  

BackgroundPatients with aneurysmal subarachnoid hemorrhage (aSAH) frequently suffer from vasospasm. We analyzed the association between absence of early angiographic vasospasm and early discharge.MethodsAll aSAH patients treated from August 1, 2007, to July 31, 2019, at a single tertiary center were reviewed. Patients undergoing diagnostic digital subtraction angiography (DSA) on post-aSAH days 5 to 7 were analyzed; cohorts with and without angiographic vasospasm (angiographic reports by attending neurovascular surgeons) were compared. Primary outcome was hospital length of stay; secondary outcomes were intensive care unit length of stay, 30 day return to the emergency department (ED), and poor neurologic outcome, defined as a modified Rankin Scale (mRS) score >2.ResultsA total of 298 patients underwent DSA on post-aSAH day 5, 6, or 7. Most patients (n=188, 63%) had angiographic vasospasm; 110 patients (37%) did not. Patients without vasospasm had a significantly lower mean length of hospital stay than vasospasm patients (18.0±7.1 days vs 22.4±8.6 days; p<0.001). The two cohorts did not differ significantly in the proportion of patients with mRS scores >2 at last follow-up or those returning to the ED before 30 days. After adjustment for Hunt and Hess scores, Fisher grade, admission Glasgow Coma Scale score, and age, logistic regression analysis showed that the absence of vasospasm on post-aSAH days 5–7 predicted discharge on or before hospital day 14 (OR 3.4, 95% CI 1.8 to 6.4, p<0.001).ConclusionLack of angiographic vasospasm 5 to 7 days after aSAH is associated with shorter hospitalization, with no increase in 30 day ED visits or poor neurologic outcome.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Sean Neifert ◽  
Alexander Schupper ◽  
Michael Martini ◽  
Emily Chapman ◽  
William Shuman ◽  
...  

Introduction: Despite their high prevalence, prospective data on medical complications after aneurysmal subarachnoid hemorrhage (aSAH) and their contribution to functional outcome are sparse. We review rates of such events and correlate them to functional outcomes in three prospective datasets of patients with aSAH. Methods: Patients from two clinical trials (NEWTON-2, CONSCIOUS-1) and one clinical registry (Subarachnoid Hemorrhage Outcomes Project) were included. A good functional outcome was defined as a Glasgow Outcomes Scale (GOS) score of 4 or 5. Seventeen medical complications were assessed and their association with functional outcomes was determined with multivariable logistic regression. The variance in outcome explained by medical complications was calculated using difference in Nagelkerke’s R-squared. Results: Among the 1,430 patients, the most common complications were fever (564, 39%), anemia (410, 29%), and pneumonia (341, 24%). Patients who suffered any complication (OR: 0.45; 95% CI: 0.36 to 0.57; p<0.001) were less likely to have a good functional outcome in unadjusted analyses. In multivariable analysis, complications independently associated with lower rates of good functional outcome were anemia (OR: 0.60; 95% CI: 0.44 to 0.80; p<0.001), cardiac arrest (OR: 0.14; 95% CI: 0.05 to 0.37; p<0.001), pneumonia (OR: 0.48; 95% CI: 0.35 to 0.66; p<0.001), pulmonary edema (OR: 0.67; 95% CI: 0.45 to 0.99; p=0.047), and acute kidney injury (OR: 0.34; 95% CI: 0.12 to 0.98; p=0.047). A panel of eleven medical complications explained 8% of the variation in functional outcomes. Conclusions: Medical complications contribute to functional outcomes after aSAH, but their individual contributions to outcomes are relatively small. This should be noted when considering trials directed at preventing or treating any one complication and raises the question of studying comprehensive neurointensive care packages in the future.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Blessing Jaja ◽  
Hester Lingsma ◽  
Ewout Steyerberg ◽  
R. Loch Macdonald ◽  

Background: Aneurysmal subarachnoid hemorrhage (SAH) is a cerebrovascular emergency. Currently, clinicians have limited tools to estimate outcomes early after hospitalization. We aimed to develop novel prognostic scores using large cohorts of patients reflecting experience from different settings. Methods: Logistic regression analysis was used to develop prediction models for mortality and unfavorable outcomes according to 3-month Glasgow outcome score after SAH based on readily obtained parameters at hospital admission. The development cohort was derived from 10 prospective studies involving 10936 patients in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository. Model performance was assessed by bootstrap internal validation and by cross validation by omission of each of the 10 studies, using R2 statistic, Area under the receiver operating characteristics curve (AUC), and calibration plots. Prognostic scores were developed from the regression coefficients. Results: Predictor variable with the strongest prognostic strength was neurologic status (partial R2 = 12.03%), followed by age (1.91%), treatment modality (1.25%), Fisher grade of CT clot burden (0.65%), history of hypertension (0.37%), aneurysm size (0.12%) and aneurysm location (0.06%). These predictors were combined to develop 3 sets of hierarchical scores based on the coefficients of the regression models. The AUC at bootstrap validation was 0.79-0.80, and at cross validation was 0.64-0.85. Calibration plots demonstrated satisfactory agreement between predicted and observed probabilities of the outcomes. Conclusions: The novel prognostic scores have good predictive ability and potential for broad application as they have been developed from prospective cohorts reflecting experience from different centers globally.


Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Andrew Silverman ◽  
Sreeja Kodali ◽  
Sumita Strander ◽  
Emily Gilmore ◽  
Alexandra Kimmel ◽  
...  

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


Sign in / Sign up

Export Citation Format

Share Document