Subarachnoid hemorrhage (SAH) carries a 50% mortality rate. The extravasated erythrocytes that surround the brain contain heme, which, when released from damaged red blood cells, functions as a ...potent danger molecule that induces sterile tissue injury and organ dysfunction. Free heme is metabolized by heme oxygenase (HO), resulting in the generation of carbon monoxide (CO), a bioactive gas with potent immunomodulatory capabilities. Here, using a murine model of SAH, we demonstrated that expression of the inducible HO isoform (HO-1, encoded by Hmox1) in microglia is necessary to attenuate neuronal cell death, vasospasm, impaired cognitive function, and clearance of cerebral blood burden. Initiation of CO inhalation after SAH rescued the absence of microglial HO-1 and reduced injury by enhancing erythrophagocytosis. Evaluation of correlative human data revealed that patients with SAH have markedly higher HO-1 activity in cerebrospinal fluid (CSF) compared with that in patients with unruptured cerebral aneurysms. Furthermore, cisternal hematoma volume correlated with HO-1 activity and cytokine expression in the CSF of these patients. Collectively, we found that microglial HO-1 and the generation of CO are essential for effective elimination of blood and heme after SAH that otherwise leads to neuronal injury and cognitive dysfunction. Administration of CO may have potential as a therapeutic modality in patients with ruptured cerebral aneurysms.
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
Flow diversion for posterior circulation aneurysms performed using the Pipeline embolization device (PED) constitutes an increasingly common off-label use for otherwise untreatable aneurysms. The ...safety and efficacy of this treatment modality has not been assessed in a multicenter study.
A retrospective review of prospectively maintained databases at 8 academic institutions was performed for the years 2009 to 2016 to identify patients with posterior circulation aneurysms treated with PED placement.
A total of 129 consecutive patients underwent 129 procedures to treat 131 aneurysms; 29 dissecting, 53 fusiform, and 49 saccular lesions were included. At a median follow-up of 11 months, complete and near-complete occlusion was recorded in 78.1%. Dissecting aneurysms had the highest occlusion rate and fusiform the lowest. Major complications were most frequent in fusiform aneurysms, whereas minor complications occurred most commonly in saccular aneurysms. In patients with saccular aneurysms, clopidogrel responders had a lower complication rate than did clopidogrel nonresponders. The majority of dissecting aneurysms were treated in the immediate or acute phase following subarachnoid hemorrhage, a circumstance that contributed to the highest mortality rate in those aneurysms.
In the largest series to date, fusiform aneurysms were found to have the lowest occlusion rate and the highest frequency of major complications. Dissecting aneurysms, frequently treated in the setting of subarachnoid hemorrhage, occluded most often and had a low complication rate. Saccular aneurysms were associated with predominantly minor complications, particularly in clopidogrel nonresponders.
Abstract
BACKGROUND
Middle meningeal artery (MMA) embolization is an emerging minimally invasive endovascular technique for chronic subdural hematoma (cSDH). Currently, limited literature exists on ...its safety and efficacy compared with conventional treatment (open-surgical-evacuation-only).
OBJECTIVE
To compare MMA embolization to conventional treatment.
METHODS
Retrospective analysis of patients with cSDHs treated with MMA embolization in a single center from 2018 to 2019 was performed. Comparisons were made with a historical conventional treatment cohort from 2006 to 2016. Propensity score matching analysis was used to assemble a balanced group of subjects.
RESULTS
A total of 357 conventionally treated cSDH and 45 with MMA embolization were included. After balancing with propensity score matching, a total of 25 pairs of cSDH were analyzed. Comparing the embolization with the conventional treatment group yielded no significant differences in complications (4% vs 4%; P > .99), clinical improvement (82.6% vs 83.3%; P = .95), cSDH recurrence (4.3% vs 21.7%; P = .08), overall re-intervention rates (12% vs 24%; P = .26), modified Rankin scale >2 on last follow-up (17.4% vs 32%; P = .24), as well as mortality (0% vs 12%; P = .09). Radiographic improvement at last follow-up was significantly higher in the open surgery cohort (73.9% vs 95.6%; P = .04). However, there was a trend for lengthier last follow-up for the historical cohort (72 vs 104 d; P = .07).
CONCLUSION
There was a trend for lower recurrence and mortality rates in the embolization era cohort. There were significantly higher radiological improvement rates on last follow-up in the surgical only cohort era. There were no significant differences in complications and clinical improvement.
Graphical Abstract
Graphical Abstract
Abstract
BACKGROUND:
The supplementary grading system for brain arteriovenous malformations (AVMs) was introduced in 2010 as a tool for improving preoperative risk prediction and selecting surgical ...patients.
OBJECTIVE:
To demonstrate in this multicenter validation study that supplemented Spetzler-Martin (SM-Supp) grades have greater predictive accuracy than Spetzler-Martin (SM) grades alone.
METHODS:
Data collected from 1009 AVM patients who underwent AVM resection were used to compare the predictive powers of SM and SM-Supp grades. Patients included the original 300 University of California, San Francisco patients plus those treated thereafter (n = 117) and an additional 592 patients from 3 other centers.
RESULTS:
In the combined cohort, the SM-Supp system performed better than SM system alone: area under the receiver-operating characteristics curve (AUROC) = 0.75 (95% confidence interval, 0.71–0.78) for SM-Supp and AUROC = 0.69 (95% confidence interval, 0.65-0.73) for SM (P < .001). Stratified analysis fitting models within 3 different follow-up groupings (<6 months, 6 months-2 years, and >2 years) demonstrated that the SM-Supp system performed better than SM system for both medium (AUROC = 0.71 vs 0.62; P = .003) and long (AUROC = 0.69 vs 0.58; P = .001) follow-up. Patients with SM-Supp grades ⩽6 had acceptably low surgical risks (0%-24%), with a significant increase in risk for grades >6 (39%-63%).
CONCLUSION:
This study validates the predictive accuracy of the SM-Supp system in a multicenter cohort. An SM-Supp grade of 6 is a cutoff or boundary for AVM operability. Supplemented grading is currently the best method of estimating neurological outcomes after AVM surgery, and we recommend it as a starting point in the evaluation of AVM operability.
Abstract
BACKGROUND
Thromboembolic and hemorrhagic complications are among the most feared adverse events in the endovascular treatment of aneurysms, and this is particularly the case for flow ...diverter devices. Dual antiplatelet therapy has become standard of care; however, the safety, efficacy, and cost profiles of newer antiplatelet agents are not well characterized in the neurovascular context.
OBJECTIVE
To compare the safety, efficacy, and cost of one of these newer agents, ticagrelor, to the most frequently used agent, clopidogrel.
METHODS
A multicenter, retrospective, cohort comparison study design of consecutively treated aneurysms with flow diverter embolization device and treated with either ticagrelor or clopidogrel was performed. Data were collected on patient demographics and risk factors, procedural details, antiplatelet treatment regime, complications, and angiographic and functional outcomes.
RESULTS
Fifty patients undergoing flow diverter device deployment and treatment with ticagrelor were compared to 53 patients undergoing flow diversion and treatment with clopidogrel. The patients’ age, sex, smoking status, aneurismal morphology and size, and procedural details did not differ between the 2 groups; neither did the rate of thromboembolic and hemorrhagic complications, angiographical, and functional outcomes. Ticagrelor was more expensive when compared to clopidogrel.
CONCLUSION
Ticagrelor is a safe and effective agent for prevention of thromboembolic complications following flow diverter deployment when compared to clopidogrel. However, ticagrelor remains significantly more expensive than clopidogrel, and, thus, we would advise ticagrelor be reserved for patients who are hyporesponsive to clopidogrel.
The prevalence of intracranial aneurysms among female cigarette smokers was shown to be high in previous studies, yet the cost-effectiveness of screening them has never been explored.
To explore the ...most cost-effective screening strategy for female smokers.
A decision analytical study was performed with a Markov model to compare different screening strategies with no screening and to explore the most optimal screening strategy for female smokers. Input data for the model were extracted from literature. A single screening at different ages and multiple screening every 15 years, 10 years, 5 years, and 2 years were performed for female smokers in different age ranges. Deterministic and probabilistic sensitivity analyses were performed to evaluate the robustness of the model. Finally, value of information analysis was performed to investigate the value of collecting additional data.
Screening female smokers for unruptured intracranial aneurysm is cost-effective. All screening strategies yield extra quality-adjusted life years. Screening at younger age brings more health benefit at lower cost. Frequent screening strategies decrease rupture rate of aneurysms more with higher costs per quality-adjusted life year. Screening after age 70 years and frequent screening (every 2 years) after age 60 years is not optimal. Among all the parameters in the model, collecting additional data on utility of the unscreened population would be most valuable.
Screening female smokers for intracranial aneurysms once at younger age is most optimal. However, in clinical practice, the duration and intensity of exposure to cigarettes should be taken into consideration.
Background Acute subdural hematoma (SDH) is a major cause of morbidity after severe traumatic brain injury. Surgical evacuation of the hematoma, either via craniotomy or craniectomy, is the mainstay ...of treatment in patients with progressive neurologic deficits or significant mass effect. However, the decision to perform either procedure remains controversial. Methods A literature search using major online databases and a manual search of references on the topic of craniotomy and craniectomy for evacuation of subdural hematoma until September 2016 was performed. The outcome variables were analyzed which included residual SDH, revision rate, and clinical outcome. Results Six comparison studies, with a total number of 2006 craniotomy and 451 craniectomy patients, fulfilled the inclusion criteria. Patients who underwent craniectomy scored significantly lower on the Glasgow Coma Scale at the time of initial presentation. Postoperatively, the rate of residual SDH was significantly lower in the craniectomy group than the craniotomy group ( P = 0.004), with no difference in the revision rate. The odds of a poor outcome at follow-up was found to be lower in the craniotomy group (50.1% vs. 60.1%, respectively; P = 0.004). Similarly, mortality rates was lower in the craniotomy group than the craniectomy group ( P = 0.004). Conclusions The safety and efficacy of craniotomy versus decompressive craniectomy in treatment of acute SDH remain controversial. In this study, craniectomy was associated with worse clinical presentation and postoperative outcome compared with craniotomy. However, craniectomy was associated with lower rate of residual SDH after treatment.
A recent systematic review indicated that gut–microbiota–brain axis contributes to growth and rupture of intracranial aneurysms. However, gaps were detected in the role of intestinal microbiome in ...cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). This is the first pilot study aiming to test study feasibility and identify differences in gut microbiota between subjects with and without CVS following aSAH. A prospective nested case–control pilot study with 1:1 matching was conducted recruiting subjects with aSAH: cases with CVS; and controls without CVS based on the clinical picture and structured bedside transcranial Doppler (TCD). Fecal samples for microbiota analyses by means of 16S rRNA gene amplicon sequencing were collected within the first 96 h after ictus. Operational taxonomic unit tables were constructed, diversity metrics calculated, phylogenetic trees built, and differential abundance analysis (DAA) performed. At baseline, the groups did not differ significantly in basic demographic and aneurysm-related characteristics (p > 0.05). Alpha-diversity (richness and Shannon Index) was significantly reduced in cases of middle cerebral artery (MCA) vasospasm (p < 0.05). In DAA, relative abundance of genus Acidaminococcus was associated with MCA vasospasm (p = 0.00013). Two butyrate-producing genera, Intestinimonas and Butyricimonas, as well as Clostridium innocuum group had the strongest negative correlation with the mean blood flow velocity in anterior cerebral arteries (p < 0.01; rho = − 0.63; − 0.57, and − 0.57, respectively). In total, 16 gut microbial genera were identified to correlate with TCD parameters, and two intestinal genera correlated with outcome upon discharge. In this pilot study, we prove study feasibility and present the first preliminary evidence of gut microbiome signature associating with CVS as a significant cause of stroke in subjects with aSAH.
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