The function of melatonin as a protective agent against newborn hypoxic‐ischemic (H‐I) brain injury is not yet well studied, and the mechanisms by which melatonin causes neuroprotection in ...neurological diseases are still evolving. This study was designed to investigate whether expression of MT1 receptors is reduced in newborn H‐I brain injury and whether the protective action of melatonin is by alterations of the MT1 receptors. We demonstrated that there was significant reduction in MT1 receptors in ischemic brain of mouse pups in vivo following H‐I brain injury and that melatonin offers neuroprotection through upregulation of MT1 receptors. The role of MT1 receptors was further supported by observation of increased mortality in MT1 knockout mice following H‐I brain injury and the reversal of the inhibitory role of melatonin on mitochondrial cell death pathways by the melatonin receptor antagonist, luzindole. These data demonstrate that melatonin mediates its neuroprotective effect in mouse models of newborn H‐I brain injury, at least in part, by the restoration of MT1 receptors, the inhibition of mitochondrial cell death pathways and the suppression of astrocytic and microglial activation.
Abstract
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.
Graphical Abstract
Graphical Abstract
Abstract
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.
Graphical Abstract
Graphical Abstract
OBJECTIVE Although aspirin usage may be associated with a decreased risk of rupture of cerebral aneurysms, any potential therapeutic benefit from aspirin must be weighed against the theoretical risk ...of greater hemorrhage volume if subarachnoid hemorrhage (SAH) occurs. However, few studies have evaluated the association between prehemorrhage aspirin use and outcomes. This is the first nationwide analysis to evaluate the impact of long-term aspirin and anticoagulant use on outcomes after SAH. METHODS Data from the Nationwide Inpatient Sample (NIS; 2006-2011) were extracted. Patients with a primary diagnosis of SAH who underwent microsurgical or endovascular aneurysm repair were included; those with a diagnosis of an arteriovenous malformation were excluded. Multivariable logistic regression was performed to calculate the adjusted odds of in-hospital mortality, a nonroutine discharge (any discharge other than to home), or a poor outcome (death, discharge to institutional care, tracheostomy, or gastrostomy) for patients with long-term aspirin or anticoagulant use. Multivariable linear regression was used to evaluate length of hospital stay. Covariates included patient age, sex, comorbidities, primary payer, NIS-SAH severity scale, intracerebral hemorrhage, cerebral edema, herniation, modality of aneurysm repair, hospital bed size, and whether the hospital was a teaching hospital. Subgroup analyses exclusively evaluated patients treated surgically or endovascularly. RESULTS The study examined 11,549 hospital admissions. Both aspirin (2.1%, n = 245) and anticoagulant users (0.9%, n = 108) were significantly older and had a greater burden of comorbid disease (p < 0.001); severity of SAH was slightly lower in those with long-term aspirin use (p = 0.03). Neither in-hospital mortality (13.5% vs 12.6%) nor total complication rates (79.6% vs 80.0%) differed significantly by long-term aspirin use. Additionally, aspirin use was associated with decreased odds of a cardiac complication (OR 0.57, 95% CI 0.36%-0.91%, p = 0.02) or of venous thromboembolic events (OR 0.53, 95% CI 0.30%-0.94%, p = 0.03). Length of stay was significantly shorter (15 days vs 17 days 12.73%, 95% CI 5.22%-20.24%, p = 0.001), and the odds of a nonroutine discharge were lower (OR 0.63, 95% CI 0.48%-0.83%, p = 0.001) for aspirin users. In subgroup analyses, the benefits of aspirin were primarily noted in patients who underwent coil embolization; likewise, among patients treated endovascularly, the adjusted odds of a poor outcome were lower among long-term aspirin users (31.8% vs 37.4%, OR 0.63, 95% CI 0.42%-0.94%, p = 0.03). Although the crude rates of in-hospital mortality (19.4% vs 12.6%) and poor outcome (53.6% vs 37.6%) were higher for long-term anticoagulant users, in multivariable logistic regression models these variations were not significantly different (mortality: OR 1.36, 95% CI 0.89%-2.07%, p = 0.16; poor outcome: OR 1.09, 95% CI 0.69%-1.73%, p = 0.72). CONCLUSIONS In this nationwide study, neither long-term aspirin nor anticoagulant use were associated with differential mortality or complication rates after SAH. Aspirin use was associated with a shorter hospital stay and lower rates of nonroutine discharge, with these benefits primarily observed in patients treated endovascularly.
Abstract
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.
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 (
<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.
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.
CONCLUSIONs—In this nationwide analysis, early decompressive craniectomy was associated with superior outcomes. However, performing decompression before herniation may be the most important temporal consideration.
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.
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.
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%).
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.
OBJECTIVE Although the prevalence of obesity is increasing rapidly both nationally and internationally, few studies have analyzed outcomes among obese patients undergoing cranial neurosurgery. The ...goal of this study, which used a nationwide data set, was to evaluate the association of both obesity and morbid obesity with treatment outcomes among patients with aneurysmal subarachnoid hemorrhage (SAH); in addition, the authors sought to analyze how postoperative complications for obese patients with SAH differ by the treatment modality used for aneurysm repair. METHODS Clinical data for adult patients with SAH who underwent microsurgical or endovascular aneurysm repair were extracted from the Nationwide Inpatient Sample (NIS). The body habitus of patients was classified as nonobese (body mass index BMI < 30 kg/m
), obese (BMI ≥ 30 kg/m
and ≤ 40 kg/m
), or morbidly obese (BMI > 40 kg/m
). Multivariable logistic regression analyzed the association of body habitus with in-hospital mortality rate, complications, discharge disposition, and poor outcome as defined by the composite NIS-SAH outcome measure. Covariates included patient demographics, comorbidities (including hypertension and diabetes), health insurance status, the NIS-SAH severity scale, treatment modality used for aneurysm repair, and hospital characteristics. RESULTS In total, data from 18,281 patients were included in this study; the prevalence of morbid obesity increased from 0.8% in 2002 to 3.5% in 2011. Obese and morbidly obese patients were significantly younger and had a greater number of comorbidities than nonobese patients (p < 0.001). Mortality rates for obese (11.5%) and morbidly obese patients (10.5%) did not significantly differ from those for nonobese patients (13.5%); likewise, no differences in neurological complications or poor outcome were observed among these 3 groups. Morbid obesity was associated with significantly increased odds of several medical complications, including venous thromboembolic (OR 1.52, 95% CI 1.01-2.30, p = 0.046) and renal (OR 1.64, 95% CI: 1.11-2.43, p = 0.01) complications and infections (OR 1.34, 95% CI 1.08-1.67, p = 0.009, attributable to greater odds of urinary tract and surgical site infections). Moreover, morbidly obese patients had higher odds of a nonroutine hospital discharge (OR 1.33, 95% CI 1.03-1.71, p = 0.03). Patients with milder obesity had decreased odds of some medical complications, including cardiac, pulmonary, and infectious complications, primarily among patients who had undergone coil embolization. CONCLUSIONS In this study involving a nationwide administrative database, milder obesity was not significantly associated with increased mortality rates, neurological complications, or poor outcomes after SAH. Morbid obesity, however, was associated with increased odds of venous thromboembolic, renal, and infectious complications, as well as of a nonroutine hospital discharge. Notably, milder obesity was associated with decreased odds of some medical complications, primarily in patients treated with coiling.
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.
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.
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.
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.
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