A Transcriptomic Comparative Study of Cranial Vasculature.

In genetic studies of cerebrovascular diseases, the optimal vessels to use as controls remain unclear. Our goal is to compare the transcriptomic profiles among 3 different types of control vessels: superficial temporal artery (STA), middle cerebral arteries (MCA), and arteries from the circle of Willis obtained from autopsies (AU). We examined the transcriptomic profiles of STA, MCA, and AU using RNAseq. We also investigated the effects of using these control groups on the results of the comparisons between aneurysms and the control arteries. Our study showed that when comparing pathological cerebral arteries to control groups, all control groups presented similar responses in the activation of immunological processes, the regulation of intracellular signaling pathways, and extracellular matrix productions, despite their intrinsic biological differences. When compared to STA, AU exhibited upregulation of stress and apoptosis genes, whereas MCA showed upregulation of genes associated with tRNA/rRNA processing. Moreover, our results suggest that the matched case-control study design, which involves control STA samples collected from the same subjects of matched aneurysm samples in our study, can improve the identification of non-inherited disease-associated genes. Given the challenges associated with obtaining fresh intracranial arteries from healthy individuals, our study suggests that using MCA, AU, or paired STA samples as controls are feasible strategies for future large-scale studies investigating cerebral vasculopathies. However, the intrinsic differences of each type of control should be taken into consideration when interpreting the results. With the limitations of each control type, it may be most optimal to use multiple tissues as controls.

Asymptomatic Moyamoya Disease in a North American Adult Cohort.

OBJECTIVE: The natural history of asymptomatic adult moyamoya disease (MMD) is unclear, and the benefit of treatment remains controversial. This study aimed to investigate the natural history of asymptomatic MMD in a North American cohort and to evaluate risk factors associated with and the effects of treatment on disease progression. METHODS: Medical records from 3 institutions of consecutive adult patients with MMD diagnosed between 1984 and 2018 were retrospectively reviewed. Patients with unilateral or bilateral asymptomatic MMD were evaluated for subsequent development of infarction or hemorrhage. Multivariate Cox proportional hazards regression assessed risk factors associated with infarction or hemorrhage, adjusting for age, sex, race, initial Suzuki grade, hypertension, hyperlipidemia, diabetes, obesity, presence of aneurysms, smoking status, aspirin, and statin use at diagnosis. RESULTS: We identified 106 hemispheres with asymptomatic MMD in 97 patients with mean 5.1 years (interquartile range, 1.0-7.9 years) of follow-up. Of 106 hemispheres, 59 were treated medically, and 47 were treated with revascularization with direct or indirect bypasses. The medical and surgical cohorts had a 1.9% and 1.3% annual rate of radiographic infarction or hemorrhage per hemisphere, respectively. Cox regression for radiographic events, including early postoperative events, showed no significant difference between the treatment groups (adjusted hazard ratio 0.34 [95% confidence interval 0.05-2.5]). CONCLUSIONS: We found an overall 1.7% annual rate of radiographic infarction or hemorrhage in asymptomatic MMD hemispheres. Although we did not find a benefit to surgical treatment within the study period, asymptomatic patients with expected long-term survival may benefit from surgery given the sustained long-term benefits after surgery despite an initial postoperative risk.

Incidence and Outcomes of Registry-Based Acute Myocardial Infarction After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Acute myocardial infarction (AMI) is the rarest and least studied cardiac complication of aneurysmal subarachnoid hemorrhage (aSAH). Precise estimates of the incidence of AMI after aSAH are unavailable. Our goal was to estimate the incidence of registry-based AMI (rb-AMI) after aSAH and determine its association with clinical outcomes. METHODS: Adult patients with aSAH in the National Inpatient Samples from 2002 to 2014 were included in the study. We evaluated risk factors for rb-AMI using univariate and multivariate regression models. Clinical outcomes that were assessed included functional status at discharge, in-patient mortality, length of stay, and total hospitalization cost, adjusting for patient demographics and cardiovascular risk factors through an inverse probability weighted analysis. Subgroup analyses were further performed stratified by rb-AMI type (ST-segment elevation myocardial infarction [STEMI] vs. non-STEMI [NSTEMI]). RESULTS: A total of 139,734 patients with aSAH were identified, 3.6% of whom had rb-AMI. NSTEMI was the most common type of rb-AMI occurring after aSAH (71% vs. 29% for NSTEMI vs. STEMI, respectively). Patient characteristics associated with higher odds of rb-AMI included age, female sex, poor aSAH grade, and various cardiovascular risk factors. Rb-AMI was also associated with poor functional status at discharge, higher in-hospital mortality, and a longer and more costly hospital stay. CONCLUSIONS: Rb-AMI occurs in 3.6% of patients with aSAH and is associated with poor functional status at discharge, higher in-patient mortality, and a longer and more costly hospitalization. Differentiating between different types of rb-AMI would be important in optimizing the management of patients with aSAH. Our definition of rb-AMI likely includes patients with neurogenic stress cardiomyopathy, which may confound the results.

Cannabis Use and Increased Nonaneurysmal Subarachnoid Hemorrhage in the Past Decade.

OBJECTIVE: Spontaneous subarachnoid hemorrhage is often due to rupture of an intracranial aneurysm, but some patients present with no identifiable source. Increased incidence of nonaneurysmal subarachnoid hemorrhage (naSAH) has been reported over time. METHODS: We performed a retrospective analysis of naSAH from 2008-2017 to determine the rate of naSAH change over time and its association with cannabis use. Univariable and multivariable regression analyses were performed to study the trend over time, radiographic patterns of hemorrhage, and clinical outcome at the time of discharge. In addition, we compared the rate of naSAH with the rate of aneurysmal SAH (aSAH) to adjust for changes in hospital volume and prevalence/reporting of cannabis use in the population over time. RESULTS: A total of 86 naSAH and 328 aSAH patients were identified, with an increase in naSAH over time compared with aSAH (P = 0.0034). Increased cannabis use was associated with naSAH (odds ratio [OR] 2.1, 95% confidence interval 1.1, 4.1, P = 0.035) but not aSAH over time. Cannabis use was also associated with different subarachnoid hemorrhage patterns (P = 0.0065) in naSAH. Multivariable analysis demonstrated good neurologic outcome after naSAH to be inversely associated with cocaine use (OR 0.008 [0.002-0.4]), ventriculostomy placement (OR 0.004 [0.03-0.50]), and anticoagulant use (OR 0.016 [0.003-0.54]) but not with cannabis use. CONCLUSIONS: As cannabis use becomes more prevalent with legalization, it is important to further investigate this association with spontaneous SAH.

Direct vs Indirect Revascularization in a North American Cohort of Moyamoya Disease.

BACKGROUND: In adults with ischemic moyamoya disease (MMD), the efficacy of direct vs indirect revascularization procedures remains a matter of debate. OBJECTIVE: To investigate the outcomes of ischemic MMD in a North American cohort treated by direct and indirect revascularizations. METHODS: We retrospectively reviewed medical records of adult patients with MMD with ischemic presentation from 1984 to 2018 at the Brigham and Women's Hospital and Massachusetts General Hospital who underwent either direct or indirect bypasses. Early postoperative events and outcome at more than 6 mo postoperatively were evaluated using multivariable logistic regression analyses. Multivariable Cox proportional hazards regression analyses were used to evaluate delayed ischemic and hemorrhagic events. Analyses were performed per hemisphere. RESULTS: A total of 95 patients with MMD and 127 hemispheres were included in this study. A total of 3.5% and 8.6% of patients had early surgical complications in the direct and indirect bypass cohorts, respectively (P = .24). Hemispheres with direct bypasses had fewer long-term ischemic and hemorrhagic events at latest follow-up (adjusted hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.058-0.63, P = .007; median follow-up 4.5 [interquartile range, IQR 1-8] yr). There was no difference between the direct and indirect bypass groups when the endpoint was limited to infarction and hemorrhage only (P = .12). There was no difference in outcome (modified Rankin Scale [mRS] ≥ 3) between the 2 cohorts (P = .92). CONCLUSION: There was no difference in early postoperative events, long-term infarction or hemorrhage, or clinical outcome between direct and indirect revascularization. However, there was a significant decrease in all ischemic and hemorrhagic events combined in direct revascularizations compared to indirect revascularizations.

Familial Predisposition and Differences in Radiographic Patterns in Spontaneous Nonaneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) from an intracranial aneurysmal rupture is the most common nontraumatic etiology for SAH, but up to 15% of patients with SAH have no identifiable source. OBJECTIVE: To assess familial predisposition to spontaneous nonaneurysmal SAH (naSAH) and to evaluate whether family history affects the severity of presentation and prognosis of this condition. METHODS: We conducted a retrospective analysis of all spontaneous SAH with negative digital subtraction angiography from 2004 to 2018. Patients were divided into 2 groups: patients with first- or second-degree relatives with intracranial aneurysms and patients with no family history. Univariate and multivariate regression analyses were used to study patient presentation, radiographic patterns of hemorrhage, and clinical outcome. RESULTS: A total of 100 patients met the inclusion criteria. There were no individuals with family history of naSAH. A total of 15 patients (15%) had at least one family member with an intracranial aneurysm, of which 12 (12%) presented as SAH. Patients without family history had a higher percentage of perimesencephalic presentation, whereas those with family history had a higher percentage of nonperimesencephalic SAH presentation (47% vs 13%, odds ratio [OR] 0.17 [95% CI 0.04, 0.81]). CONCLUSION: We found a high rate of family history of intracranial aneurysms in patients who presented with naSAH. Although there was no difference in clinical outcome in patients with and without family history, there appears to be a higher percentage of nonperimesencephalic radiographic patterns of SAH in those with family history, suggesting possible different etiologies of these hemorrhages.

Insulin in the Management of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

OBJECTIVE: The role of tight glycemic control in the management of acute ischemic stroke remains uncertain. Our goal is to evaluate the effects of tight glucose control with insulin therapy after acute ischemic stroke. METHODS: We searched PubMed, CENTRAL, and Embase for randomized controlled trials (RCTs) that evaluated the effects of tight glycemic control (70-135 mg/dL) in acute ischemic stroke. Analysis was performed using fixed-effects and random-effects models. Outcomes were death, independence, and modified Rankin Scale (mRS) score at ≥90 days follow-up, and symptomatic or severe hypoglycemia during treatment. RESULTS: Twelve RCTs including 2734 patients were included. Compared with conventional therapy or placebo, tight glycemic control was associated with similar rates of mortality at ≥90 days follow-up (pooled odds ratio [pOR], 0.99; 95% confidence interval [CI], 0.79-1.22]; I2 = 0%), independence at ≥90 days follow-up (pOR, 0.95; 95% CI, 0.79-1.14; I2 = 0%) and mRS scores at ≥90 days follow-up (standardized mean difference, 0.014; 95% CI, -0.15 to 0.17; I2 = 0%). In contrast, tight glycemic control was associated with increased rates of symptomatic or severe hypoglycemia during treatment (pOR, 5.2; 95% CI, 1.7-15.9; I2 = 28%). CONCLUSIONS: Tight glucose control after acute ischemic stroke is not associated with improvements in mortality, independence, or mRS score and leads to higher rates of symptomatic or severe hypoglycemia.

Predictive Score of Adverse Events After Carotid Endarterectomy: The NSQIP Registry Carotid Endarterectomy Scale.

Background The goal of this study was to create a comprehensive, integer-weighted predictive scale of adverse events after carotid endarterectomy (CEA), which may augment risk stratification and patient counseling. Methods and Results The targeted carotid files from the prospective NSQIP (National Surgical Quality Improvement Program) registry (2011-2013) comprised the derivation population. Multivariable logistic regression evaluated predictors of a 30-day adverse event (stroke, myocardial infarction, or death), the effect estimates of which were used to build a weighted predictive scale that was validated using the 2014 to 2015 NSQIP registry release. A total of 10 766 and 8002 patients were included in the derivation and the validation populations, in whom 4.0% and 3.7% developed an adverse event, respectively. The NSQIP registry CEA scale included 14 variables; the highest points were allocated for insulin-dependent diabetes mellitus, high-risk cardiac physiological characteristics, admission source other than home, an emergent operation, American Society of Anesthesiologists' classification IV to V, modified Rankin Scale score ≥2, and presentation with a stroke. NSQIP registry CEA score was predictive of an adverse event (concordance=0.67), stroke or death (concordance=0.69), mortality (concordance=0.76), an extended hospitalization (concordance=0.73), and a nonroutine discharge (concordance=0.83) in the validation population, as well as among symptomatic and asymptomatic subgroups (P<0.001). In the validation population, patients with an NSQIP registry CEA scale score >8 and 17 had 30-day stroke or death rates >3% and 6%, the recommended thresholds for asymptomatic and symptomatic patients, respectively. Conclusions The NSQIP registry CEA scale predicts adverse outcomes after CEA and can risk stratify patients with both symptomatic and asymptomatic carotid stenosis using different thresholds for each population.

Periprocedural intracranial hemorrhage after embolization of cerebral arteriovenous malformations: a meta-analysis.

OBJECTIVE: The primary goal of the treatment of cerebral arteriovenous malformations (AVMs) is angiographic occlusion to eliminate future hemorrhage risk. Although multimodal treatment is increasingly used for AVMs, periprocedural hemorrhage after transarterial embolization is a potential endovascular complication that is only partially understood and merits quantification. METHODS: Searching the period between 1990 and 2019, the authors of this meta-analysis queried the PubMed and Embase databases for studies reporting periprocedural hemorrhage (within 30 days) after liquid embolization (using cyanoacrylate or ethylene vinyl alcohol copolymer) of AVMs. Random effects meta-analysis was used to evaluate the pooled rate of flow-related hemorrhage (those attributed to alterations in AVM dynamics), technical hemorrhage (those related to procedural complications), and total hemorrhage. Meta-regression was used to analyze the study-level predictors of hemorrhage, including patient age, Spetzler-Martin grade, hemorrhagic presentation, embolysate used, intent of treatment (adjuvant vs curative), associated aneurysms, endovascular angiographic obliteration, year of study publication, and years the procedures were performed. RESULTS: A total of 98 studies with 8009 patients were included in this analysis, and the mean number of embolization sessions per patient was 1.9. The pooled flow-related and total periprocedural hemorrhage rates were 2.0% (95% CI 1.5%-2.4%) and 2.6% (95% CI 2.1%-3.0%) per procedure and 3.4% (95% CI 2.6%-4.2%) and 4.8% (95% CI 4.0%-5.6%) per patient, respectively. The mortality and morbidity rates associated with hemorrhage were 14.6% and 45.1%, respectively. Subgroup analyses revealed a pooled total hemorrhage rate per procedure of 1.8% (95% CI 1.0%-2.5%) for adjuvant (surgery or radiosurgery) and 4.6% (95% CI 2.8%-6.4%) for curative intent. The treatment of aneurysms (p = 0.04) and larger patient populations (p < 0.001) were significant predictors of a lower hemorrhage rate, whereas curative intent (p = 0.04), angiographic obliteration achieved endovascularly (p = 0.003), and a greater number of embolization sessions (p = 0.03) were significant predictors of a higher hemorrhage rate. There were no significant differences in periprocedural hemorrhage rates according to the years evaluated or the embolysate utilized. CONCLUSIONS: In this study-level meta-analysis, periprocedural hemorrhage was seen after 2.6% of transarterial embolization procedures for cerebral AVMs. The adjuvant use of endovascular embolization, including in the treatment of associated aneurysms and in the presurgical or preradiosurgical setting, was a study-level predictor of significantly lower hemorrhage rates, whereas more aggressive embolization involving curative intent and endovascular angiographic obliteration was a predictor of a significantly higher total hemorrhage rate.

Age-Dependent Radiographic Vasospasm and Delayed Cerebral Ischemia in Women After Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Recent literature suggests there are sex differences in delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Our study serves to compare sex differences in radiographic vasospasm, DCI, and clinical outcome after aSAH, and to determine whether there are age-dependent differences. METHODS: A total of 328 patients with ruptured cerebral aneurysms were evaluated for radiographic vasospasm, clinical deterioration, cerebral infarction, and modified Rankin Scale-determined clinical outcome at 6 months to 1 year after rupture. Multivariate regression analyses were performed to evaluate the associations between these outcome measures and sex, adjusting for age, hypertension, aneurysm location, admission Hunt and Hess grade, and modified Fisher grade. RESULTS: After multivariate adjustment, women had higher rates of radiographic vasospasm (ß = 0.35; 95% confidence interval [CI], 0.068-0.63; P = 0.015), clinical deterioration (odds ratio [OR], 2.8; 95% CI, 1.3-6.0; P = 0.008) and cerebral infarction (OR, 2.4; 95% CI, 1.0-5.5; P = 0.039), but no difference was observed in follow-up modified Rankin Scale (mRS) outcome score at 6 months to 1 year (P = 0.96). Older women (age >55 years) have a higher rate of clinical deterioration than men in the same age group (OR, 3.5; 95% CI, 1.0-12; P = 0.043). In contrast, younger women (age ≤55 years) had increased radiographic vasospasm (ß = 0.55; 95% CI, 0.17-0.93; P = 0.005) and worse mRS outcome score (ß = 0.042; 95% CI, -0.021 to 1.1; P = 0.042) compared with men. CONCLUSIONS: Female sex is associated with a higher risk of radiographic vasospasm, clinical deterioration, and cerebral infarction. Furthermore, this association appears to be age-dependent. This study further supports the unique role of sex, and highlights the need to better understand the possible role of female hormones in the development of complications of subarachnoid hemorrhage.

Adverse events after clipping of unruptured intracranial aneurysms: the NSQIP unruptured aneurysm scale.

OBJECTIVE: The complex decision analysis of unruptured intracranial aneurysms entails weighing the benefits of aneurysm repair against operative risk. The goal of the present analysis was to build and validate a predictive scale that identifies patients with the greatest odds of a postsurgical adverse event. METHODS: Data on patients who underwent surgical clipping of an unruptured aneurysm were extracted from the prospective National Surgical Quality Improvement Program registry (NSQIP; 2007-2014); NSQIP does not systematically collect data on patients undergoing intracranial endovascular intervention. Multivariable logistic regression evaluated predictors of any 30-day adverse event; variables screened included patient demographics, comorbidities, functional status, preoperative laboratory values, aneurysm location/complexity, and operative time. A predictive scale was constructed based on statistically significant independent predictors, which was validated using both NSQIP (2015-2016) and the Nationwide Inpatient Sample (NIS; 2002-2011). RESULTS: The NSQIP unruptured aneurysm scale was proposed: 1 point was assigned for a bleeding disorder; 2 points for age 51-60 years, cardiac disease, diabetes mellitus, morbid obesity, anemia (hematocrit < 36%), operative time 240-330 minutes; 3 points for leukocytosis (white blood cell count > 12,000/µL) and operative time > 330 minutes; and 4 points for age > 60 years. An increased score was predictive of postoperative stroke or coma (NSQIP: p = 0.002, C-statistic = 0.70; NIS: p < 0.001, C-statistic = 0.61), a medical complication (NSQIP: p = 0.01, C-statistic = 0.71; NIS: p < 0.001, C-statistic = 0.64), and a nonroutine discharge (NSQIP: p < 0.001, C-statistic = 0.75; NIS: p < 0.001, C-statistic = 0.66) in both validation populations. Greater score was also predictive of increased odds of any adverse event, a major complication, and an extended hospitalization in both validation populations (p ≤ 0.03). CONCLUSIONS: The NSQIP unruptured aneurysm scale may augment the risk stratification of patients undergoing microsurgical clipping of unruptured cerebral aneurysms.

Frameless Stereotactic Navigation during Insular Glioma Resection using Fusion of Three-Dimensional Rotational Angiography and Magnetic Resonance Imaging.

BACKGROUND: Perioperative cerebral infarction is a potential complication of glioma resection, of which insular tumors are at higher risk because of the proximity of middle cerebral artery branches, including the lateral lenticulostriates and long insular arteries. In this study, 3 patients received three-dimensional rotational angiography, which was fused with magnetic resonance imaging (MRI) for frameless stereotactic navigation during dominant-hemisphere insular glioma resection. METHODS: All patients obtained a preoperative catheter angiogram with a three-dimensional rotational acquisition of the ipsilateral internal carotid artery. The pixel-based axial three-dimensional angiography data, thin-cut structural MRI, tractography from diffusion tensor imaging, and expressive language activation from functional MRI were uploaded into the iPlan software (Brainlab, Heimstetten, Germany) and fused. The target tumor, regional blood vessels, adjacent functional areas, and their associated fiber tracts were segmented and overlaid on the appropriate MRI sequence. This image fusion was used preoperatively to visualize the relationship of the mass with the adjacent vasculature and intraoperatively for frameless stereotactic navigation to optimize preservation of arterial structures. RESULTS: Three patients aged 27-60 years with excellent baseline functional status presented with seizures and were found to have a large dominant-hemisphere T2 hyperintense nonenhancing insular mass. Surgical resection was performed using multimodality neuronavigation. None sustained a postoperative arterial infarction or a perioperative neurologic deficit. CONCLUSIONS: Neuronavigation using a fusion of three-dimensional rotational angiography with MRI is a technique that can be used for preoperative planning and during resection of insular gliomas to optimize preservation of adjacent arteries.

Noninfectious Fever in Aneurysmal Subarachnoid Hemorrhage: Association with Cerebral Vasospasm and Clinical Outcome.

OBJECTIVE: The purpose of this study was to evaluate the association between noninfectious fever onset and radiographic vasospasm, delayed ischemic neurologic deficit (DIND), delayed cerebral infarction (DCI), and clinical outcome in patients with aneurysmal subarachnoid hemorrhage. METHODS: We evaluated 44 patients for the association between noninfectious fever (greater than 101.5°F) and the development of radiographic vasospasm by digital subtraction angiography (DSA) and transcranial Doppler (TCD), DIND, DCI, and modified Rankin scale outcome score at 6 months to 2 years. Multivariate logistic regression analyses were performed to account for patient age, sex, admission Hunt and Hess grade, and Fisher grade. TCD was additionally used for temporal analysis. RESULTS: Noninfectious fever was significantly associated with radiographic vasospasm using both DSA (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.2-4.5; P = 0.02) and TCD (OR, 2.4; 95% CI, 1.2-5.6; P = 0.02), but it was not associated with DIND, DCI, or outcome. The maximum cross correlation between TCD velocity and temperature occurred for temperatures taken 1 day prior to TCD velocity measurement. A quadratic mixed-effects model demonstrated that TCD velocity was significantly associated with temperature from 1 day prior to TCD velocity measurement (ß = 13.5; 95% CI, 0.83-8.79, P = 0.01), posthemorrhage day (ß = 20.1; 95% CI, 2.14-7.52; P < 0.001), and (posthemorrhage day)2 (ß = -0.72; 95% CI, -0.26 to -0.11; P < 0.001). CONCLUSIONS: Noninfectious fever was associated with the development of radiographic vasospasm but not with DIND, DCI, or clinical outcome. Furthermore, there is a temporal association between the onset of noninfectious fever and radiographic vasospasm by 1 day. Fever independent of patient's infectious profile may be an early marker for the development of radiographic vasospasm.

The Timing of Tracheostomy and Outcomes After Aneurysmal Subarachnoid Hemorrhage: A Nationwide Inpatient Sample Analysis.

BACKGROUND: The goal of this study was to investigate the association of tracheostomy timing with outcomes after aneurysmal subarachnoid hemorrhage (SAH) in a national population. METHODS: Poor-grade aneurysmal SAH patients were extracted from the Nationwide Inpatient Sample (2002-2011). Multivariable linear regression was used to analyze predictors of tracheostomy timing and multivariable logistic regression was used to evaluate the association of timing of intervention with mortality, complications, and discharge to institutional care. Covariates included patient demographics, comorbidities, severity of subarachnoid hemorrhage (measured using the NIS-SAH severity scale), hospital characteristics, and other complications and length of stay. RESULTS: The median time to tracheostomy among 1380 poor-grade SAH admissions was 11 (interquartile range: 7-15) days after intubation. The mean number of days from intubation to tracheostomy in SAH patients at the hospital (p < 0.001) was the strongest predictor of tracheostomy timing for a patient, while comorbidities and SAH severity were not significant predictors. Mortality, neurologic complications, and discharge disposition did not differ significantly by tracheostomy time. However, later tracheostomy (when evaluated continuously) was associated with greater odds of pulmonary complications (p = 0.004), venous thromboembolism (p = 0.04), and pneumonia (p = 0.02), as well as a longer hospitalization (p < 0.001). Subgroup analysis only found these associations between tracheostomy timing and medical complications in patients with moderately poor grade (NIS-SAH severity scale 7-9), while there were no significant differences by timing of intervention in very poor-grade patients (NIS-SAH severity scale > 9). CONCLUSIONS: In this analysis of a large, national data set, variation in hospital practices was the strongest predictor of tracheostomy timing for an individual. In patients with moderately poor grade, later tracheostomy was independently associated with pulmonary complications, venous thromboembolism, pneumonia, and a longer hospitalization, but not with mortality, neurological complications, or discharge disposition. However, tracheostomy timing was not significantly associated with outcomes in very poor-grade patients.

Coiling Versus Microsurgical Clipping in the Treatment of Unruptured Middle Cerebral Artery Aneurysms: A Meta-Analysis.

BACKGROUND: Open microsurgical clipping of unruptured intracranial aneurysms has long been the gold standard, yet advancements in endovascular coiling techniques have begun to challenge the status quo. OBJECTIVE: To compare endovascular coiling with microsurgical clipping among adults with unruptured middle cerebral artery aneurysms (MCAA) by conducting a meta-analysis. METHODS: A systematic search was conducted from January 2011 to October 2015 to update a previous meta-analysis. All studies that reported unruptured MCAA in adults treated by microsurgical clipping or endovascular coiling were included and cumulatively analyzed. RESULTS: Thirty-seven studies including 3352 patients were included. Using the random-effects model, pooled analysis of 11 studies of microsurgical clipping (626 aneurysms) revealed complete aneurysmal obliteration in 94.2% of cases (95% confidence interval [CI] 87.6%-97.4%). The analysis of 18 studies of endovascular coiling (759 aneurysms) revealed complete obliteration in 53.2% of cases (95% CI: 45.0%-61.1%). Among clipping studies, 22 assessed neurological outcomes (2404 aneurysms), with favorable outcomes in 97.9% (95% CI: 96.8%-98.6%). Among coiling studies, 22 examined neurological outcomes (826 aneurysms), with favorable outcomes in 95.1% (95% CI: 93.1%-96.5%). Results using the fixed-effect models were not materially different. CONCLUSION: This updated meta-analysis demonstrates that surgical clipping for unruptured MCAA remains highly safe and efficacious. Endovascular treatment for unruptured MCAAs continues to improve in efficacy and safety; yet, it results in lower rates of occlusion.

Reoperation and readmission after clipping of an unruptured intracranial aneurysm: a National Surgical Quality Improvement Program analysis.

OBJECTIVE Although reoperation and readmission have been used as quality metrics, there are limited data evaluating the rate of, reasons for, and predictors of reoperation and readmission after microsurgical clipping of unruptured aneurysms. METHODS Adult patients who underwent craniotomy for clipping of an unruptured aneurysm electively were extracted from the prospective National Surgical Quality Improvement Program registry (2011-2014). Multivariable logistic regression and recursive partitioning analysis evaluated the independent predictors of nonroutine hospital discharge, unplanned 30-day reoperation, and readmission. Predictors screened included patient age, sex, comorbidities, American Society of Anesthesiologists (ASA) classification, functional status, aneurysm location, preoperative laboratory values, operative time, and postoperative complications. RESULTS Among the 460 patients evaluated, 4.2% underwent any reoperation at a median of 7 days (interquartile range [IQR] 2-17 days) postoperatively, and 1.1% required a cranial reoperation. The most common reoperation was ventricular shunt placement (23.5%); other reoperations were tracheostomy, craniotomy for hematoma evacuation, and decompressive hemicraniectomy. Independent predictors of any unplanned reoperation were age greater than 51 years and longer operative time (p ≤ 0.04). Readmission occurred in 6.3% of patients at a median of 6 days (IQR 5-13 days) after discharge from the surgical hospitalization; 59.1% of patients were readmitted within 1 week and 86.4% within 2 weeks of discharge. The most common reason for readmission was seizure (26.7%); other causes of readmission included hydrocephalus, cerebrovascular accidents, and headache. Unplanned readmission was independently associated with age greater than 65 years, Class II or III obesity (body mass index > 35 kg/m2), preoperative hyponatremia, and preoperative anemia (p ≤ 0.04). Readmission was not associated with operative time, complications during the surgical hospitalization, length of stay, or discharge disposition. Recursive partitioning analysis identified the same 4 variables, as well as ASA classification, as associated with unplanned readmission. The most potent predictors of nonroutine hospital discharge (16.7%) were postoperative neurological and cardiopulmonary complications; other predictors were age greater than 51 years, preoperative hyponatremia, African American and Asian race, and a complex vertebrobasilar circulation aneurysm. CONCLUSIONS In this national analysis, patient age greater than 65 years, Class II or III obesity, preoperative hyponatremia, and anemia were associated with adverse events, highlighting patients who may be at risk for complications after clipping of unruptured cerebral aneurysms. The preponderance of early readmissions highlights the importance of early surveillance and follow-up after discharge; the frequency of readmission for seizure emphasizes the need for additional data evaluating the utility and duration of postcraniotomy seizure prophylaxis. Moreover, readmission was primarily associated with preoperative characteristics rather than metrics of perioperative care, suggesting that readmission may be a suboptimal indicator of the quality of care received during the surgical hospitalization in this patient population.

Cigarette smoking and outcomes after aneurysmal subarachnoid hemorrhage: a nationwide analysis.

OBJECTIVE Although cigarette smoking is one of the strongest risk factors for cerebral aneurysm development and rupture, there are limited data evaluating the impact of smoking on outcomes after aneurysmal subarachnoid hemorrhage (SAH). Additionally, two recent studies suggested that nicotine replacement therapy was associated with improved neurological outcomes among smokers who had sustained an SAH compared with smokers who did not receive nicotine. METHODS Patients who underwent endovascular or microsurgical repair of a ruptured cerebral aneurysm were extracted from the Nationwide Inpatient Sample (NIS, 2009-2011) and stratified by cigarette smoking. Multivariable logistic regression analyzed in-hospital mortality, complications, tracheostomy or gastrostomy placement, and discharge to institutional care (a nursing or an extended care facility). Additionally, the composite NIS-SAH outcome measure (based on mortality, tracheostomy or gastrostomy, and discharge disposition) was evaluated, which has been shown to have excellent agreement with a modified Rankin Scale score greater than 3. Covariates included in regression constructs were patient age, sex, race/ethnicity, insurance status, socioeconomic status, comorbidities (including hypertension, drug and alcohol abuse), the NIS-SAH severity scale (previously validated against the Hunt and Hess grade), treatment modality used for aneurysm repair, and hospital characteristics. A sensitivity analysis was performed matching smokers to nonsmokers on age, sex, number of comorbidities, and NIS-SAH severity scale score. RESULTS Among the 5784 admissions evaluated, 37.1% (n = 2148) had a diagnosis of tobacco use, of which 31.1% (n = 1800) were current and 6.0% (n = 348) prior tobacco users. Smokers were significantly younger (mean age 51.4 vs 56.2 years) and had more comorbidities compared with nonsmokers (p < 0.001). There were no significant differences in mortality, total complications, or neurological complications by smoking status. However, compared with nonsmokers, smokers had significantly decreased adjusted odds of tracheostomy or gastrostomy placement (11.9% vs 22.7%, odds ratio [OR] 0.63, 95% confidence interval [CI] 0.51-0.78, p < 0.001), discharge to institutional care (OR 0.71, 95% CI 0.57-0.89, p = 0.002), and a poor outcome (OR 0.65, 95% CI 0.55-0.77, p < 0.001). Similar statistical associations were noted in the matched-pairs sensitivity analysis and in a subgroup of poor-grade patients (the upper quartile of the NIS-SAH severity scale). CONCLUSIONS In this nationwide study, smokers experienced SAH at a younger age and had a greater number of comorbidities compared with nonsmokers, highlighting the negative ramifications of cigarette smoking among patients with cerebral aneurysms. However, smoking was also associated with paradoxical superior outcomes on some measures, and future research to confirm and further understand the basis of this relationship is needed.

Pediatric Intracranial Aneurysms: Considerations and Recommendations for Follow-Up Imaging.

BACKGROUND: Pediatric intracranial aneurysms (IAs) are rare. Compared with adult IAs, they are more commonly giant, fusiform, or dissecting. Treatment often proves more complex, and recurrence rate and de novo aneurysmogenesis incidence are higher. A consensus regarding the most appropriate algorithm for following pediatric IAs is lacking. METHODS: We sought to generate recommendations based on the reported experience in the literature with pediatric IAs through a thorough review of the PubMed database, discussion with experienced neurointerventionalists, and our own experience. RESULTS: Digital subtraction angiography (DSA) was utilized immediately post-operatively for microsurgically-clipped and endovascularly-treated IAs, at 6-12 months postoperatively for endovascularly-treated IAs, and in cases of aneurysmal recurrence or de novo aneurysmogenesis discovered by non-invasive imaging modalities. Computed tomographic angiography was the preferred imaging modality for long-term follow-up of microsurgically clipped IAs. Magnetic resonance angiography (MRA) was the preferred modality for following IAs that were untreated, endovascularly-treated, or microsurgically-treated in a manner other than clipping. CONCLUSIONS: We propose incidental untreated IAs to be followed by magnetic resonance angiography without contrast enhancement. Follow-up modality and interval for treated pediatric IAs is determined by initial aneurysmal complexity, treatment modality, and degree of posttreatment obliteration. Recurrence or de novo aneurysmogenesis requiring treatment should be followed by digital subtraction angiography and appropriate retreatment. Computed tomography angiography is preferred for clipped IAs, whereas contrast-enhanced magnetic resonance angiography is preferred for lesions treated endovascularly with coil embolization and lesions treated microsurgically in a manner other than clipping.

Readmission After Aneurysmal Subarachnoid Hemorrhage: A Nationwide Readmission Database Analysis.

BACKGROUND AND PURPOSE: The goal of this nationwide study is to evaluate the suitability of readmission as a quality indicator in the aneurysmal subarachnoid hemorrhage (SAH) population. METHODS: Patients with aneurysmal SAH were extracted from the Nationwide Readmission Database (2013). Multivariable Cox proportional hazard regression was used to evaluate predictors of a 30-day readmission, and multivariable linear regression was used to analyze the association of hospital readmission rates with hospital mortality rates. Predictors screened included patient demographics, comorbidities, severity of SAH, complications from the SAH hospitalization, and hospital characteristics. RESULTS: The 30-day readmission rate was 10.2% (n=346) among the 3387 patients evaluated, and the most common reasons for readmission were neurological, hydrocephalus, infectious, and venous thromboembolic complications. Greater number of comorbidities, increased severity of SAH, and discharge disposition other than to home were independent predictors of readmission (P≤0.03). Although hydrocephalus during the SAH hospitalization was associated with readmission for the same diagnosis, other readmissions were not associated with having sustained the same complication during the SAH hospitalization. Hospital mortality rate was inversely associated with hospital SAH volume (P=0.03) but not significantly associated with hospital readmission rate; hospital SAH volume was also not associated with SAH readmissions. CONCLUSIONS: In this national analysis, readmission was primarily attributable to new medical complications in patients with greater comorbidities and severity of SAH rather than exacerbation of complications from the SAH hospitalization. Additionally, hospital readmission rates did not correlate with other established quality metrics. Therefore, readmission may be a suboptimal quality indicator in the SAH population.

Timing of Decompressive Hemicraniectomy for Stroke: A Nationwide Inpatient Sample Analysis.

BACKGROUND AND PURPOSE: Previous clinical trials were not designed to discern the optimal timing of decompressive craniectomy for stroke, and the ideal surgical timing in patients with space-occupying infarction who do not exhibit deterioration within 48 hours is debated. METHODS: Patients undergoing decompressive craniectomy for stroke were extracted from the Nationwide Inpatient Sample (2002-2011). Multivariable logistic regression evaluated the association of surgical timing with mortality, discharge to institutional care, and poor outcome (a composite end point including death, tracheostomy and gastrostomy, or discharge to institutional care). Covariates included patient demographics, comorbidities, year of admission, and hospital characteristics. However, standard stroke severity scales and infarct volume were not available. RESULTS: Among 1301 admissions, 55.8% (n=726) underwent surgery within 48 hours. Teaching hospital admission was associated with earlier surgery (P=0.02). The timing of intervention was not associated with in-hospital mortality. However, when evaluated continuously, later surgery was associated with increased odds of discharge to institutional care (odds ratio, 1.17; 95% confidence interval, 1.05-1.31, P=0.005) and of a poor outcome (odds ratio, 1.12; 95% confidence interval, 1.02-1.23; P=0.02). When evaluated dichotomously, the odds of discharge to institutional care and of a poor outcome did not differ at 48 hours after hospital admission, but increased when surgery was pursued after 72 hours. Subgroup analyses found no association of surgical timing with outcomes among patients who had not sustained herniation. CONCLUSION: s-In this nationwide analysis, early decompressive craniectomy was associated with superior outcomes. However, performing decompression before herniation may be the most important temporal consideration.