Hypothermia is Associated with Improved Neurological Outcomes After Mechanical Thrombectomy.

BACKGROUND: Acute ischemic stroke (AIS) is the second leading cause of death globally. Mechanical thrombectomy (MT) has improved patient prognosis but expedient treatment is still necessary to minimize anoxic injury. Lower intraoperative body temperature decreases cerebral oxygen demand, but the role of hypothermia in treatment of AIS with MT is unclear. METHODS: We retrospectively reviewed patients undergoing MT for AIS from 2014 to 2020 at our institution. Patient demographics, comorbidities, intraoperative parameters, and outcomes were collected. Maximum body temperature was extracted from minute-by-minute anesthesia readings, and patients with maximal temperature below 36°C were considered hypothermic. Risk factors were assessed by χ2 and multivariate ordinal regression. RESULTS: Of 68 patients, 27 (40%) were hypothermic. There was no significant association of hypothermia with patient age, comorbidities, time since last known well, number of passes intraoperatively, favorable revascularization, tissue plasminogen activator use, and immediate postoperative complications. Hypothermic patients exhibited better neurologic outcome at 3-month follow-up (P = 0.02). On multivariate ordinal regression, lower maximum intraoperative body temperature was associated with improved 3-month outcomes (P < 0.001), when adjusting for other factors influencing neurological outcomes. Other significant protective factors included younger age (P = 0.03), better revascularization (P = 0.03), and conscious sedation (P = 0.02). CONCLUSIONS: Lower intraoperative body temperature during MT was independently associated with improved neurological outcome in this single center retrospective series. These results may help guide clinicians in employing therapeutic hypothermia during MT to improve long-term neurologic outcomes from AIS, although larger studies are needed.

No Delayed Ruptures on Long-Term Follow-Up of a Case Series of Persistently Filling Saccular Internal Carotid Artery Aneurysms After Flow Diversion With the Pipeline Embolization Device.

BACKGROUND AND OBJECTIVES: Flow diversion of intracranial aneurysms results in high occlusion rates. However, 10% to 20% remain persistently filling at 1 year. Often, these are retreated, but benefits of retreatment are not well established. A better understanding of the long-term rupture risk of persistently filling aneurysms after flow diversion is needed. METHODS: Our institutional database of 974 flow diversion cases was queried for persistently filling saccular aneurysms of the clinoidal, ophthalmic, and communicating segments of the internal carotid artery treated with the pipeline embolization device (PED, Medtronic). Persistent filling was defined as continued flow into the aneurysm on 1 year catheter angiogram. The clinical record was queried for retreatments and delayed ruptures. Clinical follow-up was required for at least 2 years. RESULTS: Ninety-four persistent aneurysms were identified. The average untreated aneurysm size was 5.6 mm. A branch vessel originated separately in 55% of cases from the body of the aneurysm in 10.6% of cases and from the neck in 34% of cases. Eighteen percent of aneurysms demonstrated >95% filling at 1 year, and 61% were filling 5% to 95% of their original size. The mean follow-up time was 4.9 years, including 41 cases with >5 years. No retreatment was undertaken in 91.5% of aneurysms. There were no cases of delayed subarachnoid hemorrhage. CONCLUSION: Among saccular internal carotid artery aneurysms treated with PED that demonstrated persistent aneurysm filling at 1 year, there were no instances of delayed rupture on long-term follow-up. These data suggest that observation may be appropriate for continued aneurysm filling at least in the first several years after PED placement.

Vertebral-Venous fistulas: Single center experience and practical treatment approach.

BACKGROUND: Vertebral-venous fistulas (VVFs) are rare. Scarce literature exists to guide our understanding and management. We report our experience and propose a classification based on flow, feeder number, and involvement of accessible veins. Additionally, we include a practical treatment approach. METHODS: Retrospective chart and imaging review of cerebrovascular arteriovenous fistulas treated in our center between July 2013 and April 2022. We reviewed patient demographics, presentation, imaging, treatment strategies, and outcomes. RESULTS: Nine patients with VVFs were identified, six were females. Ages ranged between 38-83 years. There were six high-flow and three low-flow. Most VVFs originated at the level of V3. Additional feeders from the internal carotid artery, external carotid artery, and/or subclavian artery were present in four cases (two were high-flow). Four cases had multiple arterial feeders. All cases were symptomatic. Origin was spontaneous in eight and iatrogenic in one case. Most common presenting symptoms were pain (7) and pulsatile tinnitus (4). Neurological deficits were present in two cases (1 high- and 1 low-flow). Four cases were treated with vertebral artery segmental sacrifice alone, three required multiple transarterial embolizations with or without VA sacrifice, one case had single transvenous approach, and one was treated with single targeted transarterial embolization. One patient had a minor transient neurological complication. No treatment-related mortality was seen. CONCLUSION: Treatment of high-flow and symptomatic low-flow VVFs is feasible and safe. Our classification and treatment approach might help guide patient selection and choice of endovascular approach. However, our approach warrants further validation with a larger number of patients.

Safety and efficacy results of the Flow Redirection Endoluminal Device (FRED) stent system in the treatment of intracranial aneurysms: US pivotal trial.

OBJECTIVE: To evaluate the safety and effectiveness of the Flow Redirection Endoluminal Device (FRED) flow diverter in support of an application for Food and Drug Administration approval in the USA. METHODS: 145 patients were enrolled in a prospective, single-arm multicenter trial. Patients with aneurysms of unfavorable morphology for traditional endovascular therapies (large, wide-necked, fusiform, etc) were included. The trial was designed to demonstrate non-inferiority in both safety and effectiveness, comparing trial results with performance goals (PGs) established from peer-reviewed published literature. The primary safety endpoint was death or major stroke (National Institutes of Health Stroke Scale score ≥4 points) within 30 days of the procedure, or any major ipsilateral stroke or neurological death within the first year. The primary effectiveness endpoint was complete occlusion of the target aneurysm with ≤50% stenosis of the parent artery at 12 months after treatment, and in which an alternative treatment of the target intracranial aneurysm had not been performed. RESULTS: 145 patients underwent attempted placement of a FRED device, and one or more devices were placed in all 145 patients. 135/145 (93%) had a single device placed. Core laboratory adjudication deemed 106 (73.1%) of the aneurysms large or giant. A safety endpoint was experienced by 9/145 (6.2%) patients, successfully achieving the safety PG of <15%. The effectiveness PG of >46% aneurysm occlusion was also achieved, with the effectiveness endpoint being met in 80/139 (57.6%) CONCLUSION: As compared with historically derived performance benchmarks, the FRED flow diverter is both safe and effective for the treatment of appropriately selected intracranial aneurysms. CLINICAL REGISTRATION NUMBER: NCT01801007.

Combined Pipeline Embolization Device with Endoscopic Endonasal Fascia Lata/Muscle Graft Repair as a Salvage Technique for Treatment of Iatrogenic Carotid Artery Pseudoaneurysm.

The incidence of internal carotid artery (ICA) injury associated with endoscopic endonasal approaches to the pituitary is less than 1%. While parent vessel sacrifice has historically been the choice of treatment, vessel-preserving endovascular techniques have been reported. Although flow diversion offers endoluminal reconstruction, its major limitation is the delay in obtaining complete occlusion. We describe the use of a combined Pipeline embolization device (PED) with endoscopic endonasal repair using a fascia lata/muscle graft to treat an iatrogenic ICA pseudoaneurysm and report long-term radiographic follow-up. Further investigation into the utility of directed endoscopic endonasal repair of iatrogenic pseudoaneurysms initially treated with PED is necessary, especially given the need of post-PED anticoagulation and the rate of permanent neurological deficit after ICA sacrifice.

Neuroprotective Role of Acidosis in Ischemia: Review of the Preclinical Evidence.

Efforts to develop effective neuroprotective therapies for ischemic stroke have had little success to date. One promising approach to neuroprotection is ischemic postconditioning, which utilizes brief bouts of ischemia after acute ischemic stroke to elicit neuroprotection, although the mechanism is largely unknown. As the primary components of transient ischemia are local hypoxia and acidosis, and hypoxic postconditioning has had little success, it is possible that the acidosis component may be the primary driver. To address the evidence behind this, we performed a systematic review of preclinical studies focused on the neuroprotective role of transient acidosis after ischemia. Animal studies demonstrated that mild-to-moderate acidosis after ischemic events led to better functional neurologic outcomes with reduced infarct volumes, while severe acidosis often led to cerebral edema and worse functional outcomes. In vitro studies demonstrated that mild-to-moderate acidosis improves neuronal survival largely through two means: (1) inhibition of harmful superoxide formation in the excitotoxic pathway and (2) remodeling neuronal mitochondria to allow for efficient ATP production (i.e., oxidative phosphorylation), even in the absence of oxygen. Similar to the animal studies, acidotic postconditioning in humans would entail short cycles of carbon dioxide inhalation, which has already been demonstrated to be safe as part of a hypercapnic challenge when measuring cerebrovascular reactivity. Due to the preclinical efficacy of acidotic postconditioning, its relatively straightforward translation into humans, and the growing need for neuroprotective therapies, future preclinical studies should focus on filling the current knowledge gaps that are currently restricting the development of phase I/II clinical trials.

Application of unruptured aneurysm scoring systems to a cohort of ruptured aneurysms: are we underestimating rupture risk?

The predictive values of current risk stratification scales such as the Unruptured Intracranial Aneurysm Treatment Score (UIATS) and the PHASES score are debatable. We evaluated these scores using a cohort of ruptured intracranial aneurysms to simulate their management recommendations had the exact same patients presented prior to rupture. A prospectively maintained database of ruptured saccular aneurysm patients presenting to our institution was used. The PHASES score was calculated for 992 consecutive patients presenting between January 2002 and December 2018, and the UIATS was calculated for 266 consecutive patients presenting between January 2013 and December 2018. A shorter period was selected for the UIATS cohort given the larger number of variables required for calculation. Clinical outcomes were compared between UIATS-recommended "observation" aneurysms and all other aneurysms. Out of 992 ruptured aneurysms, 54% had a low PHASES score (≤5). Out of the 266 ruptured aneurysms, UIATS recommendations were as follows: 68 (26%) "observation," 97 (36%) "treatment," and 101 (38%) "non-definitive." The UIATS conservative group of patients developed more SAH-related complications (78% vs. 65%, p=0.043), had a higher rate of non-home discharge (74% vs. 46%, p<0.001), and had a greater incidence of poor functional status (modified Rankin scale >2) after 12-18 months (68% vs. 51%, p=0.014). Current predictive scoring systems for unruptured aneurysms may underestimate future rupture risk and lead to more conservative management strategies in some patients. Patients that would have been recommended for conservative therapy were more likely to have a worse outcome after rupture.

Monocyte-based inflammatory indices predict outcomes following aneurysmal subarachnoid hemorrhage.

The contribution of specific immune cell populations to the post-hemorrhagic inflammatory response in aneurysmal subarachnoid hemorrhage (aSAH) and correlations with clinical outcomes, such as vasospasm and functional status, remains unclear. We aimed to compare the predictive value of leukocyte ratios that include monocytes as compared to the neutrophil-to-lymphocyte ratio (NLR) in aSAH. A prospectively accrued database of consecutive patients presenting to our institution with aSAH between January 2013 and December 2018 was used. Patients with signs and symptoms of infection (day 1-3) were excluded. Admission values of the NLR, monocyte-neutrophil-to-lymphocyte ratio (M-NLR), and lymphocyte-to-monocyte ratio (LMR) were calculated. Associations with functional status, the primary outcome, and vasospasm were evaluated using univariable and multivariable logistic regression analyses. In the cohort of 234 patients with aSAH, the M-NLR and LMR, but not the NLR, were significantly associated with poor functional status (modified Rankin scale > 2) at 12-18 months following discharge (p = 0.001, p = 0.023, p = 0.161, respectively). The area under the curve for predicting poor functional status was significantly lower for the NLR (0.543) compared with the M-NLR (0.603, p = 0.024) and LMR (0.608, p = 0.040). The M-NLR (OR = 1.01 [1.01-1.02]) and LMR (OR = 0.88 [0.78-0.99]) were independently associated with poor functional status while controlling for age, hypertension, Fisher grade, and baseline clinical status. The LMR was significantly associated with vasospasm (OR = 0.84 [0.70-0.99]) while adjusting for age, hypertension, Fisher grade, aneurysm size, and current smoking. Inflammatory indices that incorporate monocytes (e.g., M-NLR and LMR), but not those that include only neutrophils, predict outcomes after aSAH.

Aging Patient Population With Ruptured Aneurysms: Trend Over 28 Years.

BACKGROUND: Given increasing life expectancy in the United States and worldwide, the proportion of elderly patients affected by aneurysmal subarachnoid hemorrhage (aSAH) would be expected to increase. OBJECTIVE: To determine whether an aging trend exists in the population of aSAH patients presenting to our institution over a 28-yr period. METHODS: A prospectively maintained database of consecutive patients presenting to our institution with subarachnoid hemorrhage between January 1991 and December 2018 was utilized. The 28-yr period was categorized into 4 successive 7-yr quarter intervals. The age of patients was compared among these intervals, and yearly trends were derived using linear regression. RESULTS: The cohort consisted of 1671 ruptured aneurysm patients with a mean age of 52.8 yr (standard deviation = 15.0 yr). Over the progressive 7-yr time intervals during the 28-yr period, there was an approximately 4-fold increase in the proportion of patients aged 80 yr or above (P < .001) and an increase in mean patient age from 51.2 to 54.6 yr (P = .002). Independent of this trend but along the same lines, there was a 29% decrease in the proportion of younger patients (<50 yr) from 49% to 35%. On linear regression, there was 1-yr increase in mean patient age per 5 calendar years (P < .001). CONCLUSION: Analyses of aSAH patients demonstrate an increase in patient age over time with a considerable rise in the proportion of octogenarian patients and a decrease in patients younger than 50 yr. This aging phenomenon presents a challenge to the continued improvement in outcomes of aSAH patients.

PD-1+ Monocytes Mediate Cerebral Vasospasm Following Subarachnoid Hemorrhage.

BACKGROUND: Cerebral vasospasm is a major source of morbidity and mortality following aneurysm rupture and has limited treatment options. OBJECTIVE: To evaluate the role of programmed death-1 (PD-1) in cerebral vasospasm. METHODS: Endovascular internal carotid artery perforation (ICAp) was used to induce cerebral vasospasm in mice. To evaluate the therapeutic potential of targeting PD-1, programmed death ligand-1 (PD-L1) was administered 1 h after ICAp and vasospasm was measured histologically at the level of the ICA bifurcation bilaterally. PD-1 expressing immune cell populations were evaluated by flow cytometry. To correlate these findings to patients and evaluate the potential of PD-1 as a biomarker, monocytes were isolated from the peripheral blood and analyzed by flow cytometry in a cohort of patients with ruptured cerebral aneurysms. The daily frequency of PD-1+ monocytes in the peripheral blood was correlated to transcranial Doppler velocities as well as clinical and radiographic vasospasm. RESULTS: We found that PD-L1 administration prevented cerebral vasospasm by inhibiting ingress of activated Ly6c+ and CCR2+ monocytes into the brain. Human correlative studies confirmed the presence of PD-1+ monocytes in the peripheral blood of patients with ruptured aneurysms and the frequency of these cells corresponded with cerebral blood flow velocities and clinical vasospasm. CONCLUSION: Our results identify PD-1+ monocytes as mediators of cerebral vasospasm and support PD-1 agonism as a novel therapeutic strategy.

Five-year results of randomized bioactive versus bare metal coils in the treatment of intracranial aneurysms: the Matrix and Platinum Science (MAPS) Trial.

BACKGROUND: No randomized trial of intracranial aneurysm coiling has compared long-term efficacy of polymer-modified coils to bare metal coils (BMCs). We report 5-year results comparing Matrix2 coils to BMCs. The primary objective was to compare the rates of target aneurysm recurrence (TAR) at 12 months. Secondary objectives included angiographic outcomes at TAR or 12 months and TAR at 5 years. METHODS: A total of 626 patients were randomized to BMCs or Matrix2 coils. Detailed methods and 1-year results have been published previously. RESULTS: Of 580 patients eligible for 5-year follow-up, 431 (74.3%) completed follow-up or reached TAR. Matrix2 coils were non-inferior to BMCs (P=0.8) but did not confer any benefit. Core lab reported post-treatment residual aneurysm filling (Raymond III) correlated with TAR (P<0.0001) and with aneurysm hemorrhage after treatment (P<0.008). Repeat aneurysmal hemorrhage after treatment, but before hospital discharge, occurred in three patients treated for acutely ruptured aneurysms. Additionally, two patients treated for unruptured aneurysms experienced a first hemorrhage during follow-up. All five hemorrhages resulted from aneurysms with Raymond III residual aneurysm filling persisting after initial treatment. After 5 years follow-up, 2/626 (0.3%) patients are known to have had target aneurysm rupture following hospital discharge. The annualized rate of delayed hemorrhage after coiling was 2/398/5=0.001 (0.1%) per year for unruptured aneurysms and 0 for ruptured aneurysms. CONCLUSIONS: After 5 years Matrix2 coils were non-inferior to BMCs but no benefit was demonstrated. Post-treatment residual angiographic aneurysm filling (Raymond III) is strongly associated with TAR (P<0.0001) and post-treatment aneurysmal hemorrhage (P=0.008).

Management of unruptured intracranial aneurysms: correlation of UIATS, ELAPSS, and PHASES with referral center practice.

Concordance between the Unruptured Intracranial Aneurysm Treatment Score (UIATS), Earlier Subarachnoid Hemorrhage, Location, Age, Population, Size, Shape (ELAPSS) score, and Population, Hypertension, Age, Size, Earlier Subarachnoid Hemorrhage, Site (PHASES) score with real-world management decisions in unruptured intracranial aneurysms (UIAs) remains unclear, especially in current practice. This study aimed to investigate this concordance, while developing an optimal model predictive of recent decision practices at a quaternary referral center. A prospective database of patients presenting with UIAs to our institution from January 1 to December 31, 2018, was used. Concordance between the scores and real-world management decisions on every UIA was assessed. Complications and length of stay (LOS) were compared between aneurysms in the UIATS-recommended treatment and observation groups. A subgroup analysis of concordance was also conducted among junior and senior surgeons. An optimal logistic regression model predictive of real-world decisions was also derived. The cohort consisted of 198 patients with 271 UIAs, of which 42% were treated. The UIATS demonstrated good concordance with an AUC of 0.765. Of the aneurysms in the UIATS-recommended "observation" group, 22% were discordantly treated. The ELAPSS score demonstrated good discrimination (AUC = 0.793), unlike the PHASES score (AUC = 0.579). Endovascular treatment rates, complications, and LOS were similar between aneurysms in the UIATS-recommended treatment and observation groups. Similar concordance was obtained among junior and senior surgeons. The optimal predictive model consisted of several significantly associated variables and had an AUC of 0.942. Cerebrovascular specialists may be treating aneurysms slightly more than these scores would recommend, independently of years in practice. Wide variation still exists in management practices of UIAs.

Mechanical Thrombectomy for Acute Ischemic Stroke: Considerations in Children.

The use of mechanical thrombectomy for the treatment of acute childhood arterial ischemic stroke with large vessel occlusion is increasing, with mounting evidence for its feasibility and safety. Despite this emerging evidence, clear guidelines for patient selection, thrombectomy technique, and postprocedure care do not exist for the pediatric population. Due to unique features of stroke in children, neurologists and interventionalists must consider differences in patient size, anatomy, collateral vessels, imaging parameters, and expected outcomes that may impact appropriate patient selection and timing criteria. In addition, different causes of stroke and comorbidities in children must be considered and may alter the safety and efficacy of thrombectomy. To optimize the success of endovascular intervention in children, a multidisciplinary team should take into account these nuanced considerations when determining patient eligibility, developing a procedural approach, and formulating a postprocedure neurological monitoring and therapeutic plan.

Predictors of an academic career among fellowship-trained open vascular and endovascular neurosurgeons.

OBJECTIVE: Although previous studies have explored factors that predict an academic career among neurosurgery residents in general, such predictors have yet to be determined within specific neurosurgical subspecialties. The authors report on predictors they identified as correlating with academic placement among fellowship-trained vascular neurosurgeons. METHODS: A database was created that included all physicians who graduated from ACGME (Accreditation Council for Graduate Medical Education)-accredited neurosurgery residency programs between 1960 and 2018 using publicly available online data. Neurosurgeons who completed either open vascular or endovascular fellowships were identified. Subsequent employment of vascular or endovascular neurosurgeons in academic centers was determined. A position was considered academic if the hospital of employment was affiliated with a neurosurgery residency program; all other positions were considered non-academic. Bivariate analyses were conducted using Fisher's exact test or the Mann-Whitney U-test, and multivariate analysis was performed using a logistic regression model. RESULTS: A total of 83 open vascular neurosurgeons and 115 endovascular neurosurgeons were identified. In both cohorts, the majority of neurosurgeons were employed in academic positions after training. In bivariate analysis, only 2 factors were significantly associated with a career in academic neurosurgery for open vascular neurosurgeons: 1) an h-index of ≥ 2 during residency (OR 3.71, p = 0.016), and 2) attending a top 10 residency program based on U.S. News and World Report rankings (OR 4.35, p = 0.030). In bivariate analysis, among endovascular neurosurgeons, having an h-index of ≥ 2 during residency (OR 4.35, p = 0.0085) and attending a residency program affiliated with a top 10 U.S. News and World Report medical school (OR 2.97, p = 0.029) were significantly associated with an academic career. In multivariate analysis, for both open vascular and endovascular neurosurgeons, an h-index of ≥ 2 during residency was independently predictive of an academic career. Attending a residency program affiliated with a top 10 U.S. News and World Report medical school independently predicted an academic career among endovascular neurosurgeons only. CONCLUSIONS: The authors report that an h-index of ≥ 2 during residency predicts pursuit of an academic career among vascular and endovascular neurosurgeons. Additionally, attendance of a residency program affiliated with a top research medical school independently predicts an academic career trajectory among endovascular neurosurgeons. This result may be useful to identify and mentor residents interested in academic vascular neurosurgery.

Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke. METHODS: For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018. FINDINGS: Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups. INTERPRETATION: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo. FUNDING: Canadian Institutes for Health Research, Alberta Innovates, and NoNO.

External Validation of the Subarachnoid Hemorrhage International Trialists (SAHIT) Predictive Model Using the Barrow Ruptured Aneurysm Trial (BRAT) Cohort.

BACKGROUND: The Subarachnoid Hemorrhage International Trialists (SAHIT) repository is a collection of randomized clinical trials, prospective observational studies, and hospital registries that was used to create a predictive model of unfavorable outcome/mortality following aneurysmal SAH. OBJECTIVE: To externally validate the SAHIT model using Barrow Ruptured Aneurysm Trial (BRAT) data, which was not included in the SAHIT repository. METHODS: This is a post hoc analysis of the prospective, randomized BRAT. Three models were created: (1) Core (age, hypertension, World Federation of Neurosurgical Societies grade), (2) neuroimaging (aneurysm size/location, Fisher score), and (3) full model (model 1 and 2 plus treatment type). The performance of the models was evaluated by measures of model discrimination (area under the curve [AUC]) and model calibration (goodness of fit test, calibration in-the-large, calibration slope). RESULTS: A total of 338 patients (average age 54 years; 67.7% good clinical grade; average aneurysm size 6.7 mm; 84.1% anterior circulation) were included. Due to a large number of crossovers, more aneurysms were clipped than coiled (67.5% vs 32.5%, respectively). A total of 10.1% of the patients died and 29.6% experienced an unfavorable outcome. For unfavorable outcome, the AUCs for the three models were: 0.728, 0.732, and 0.734, respectively. For mortality, the AUCs for the three models were: 0.721, 0.739, and 0.744, respectively. Overall, all models showed good calibration, and the measures of calibration fell within 95% CI of those produced in the SAHIT study. CONCLUSION: Using the BRAT data, we have externally validated the SAHIT model for predicting unfavorable outcome and mortality after SAH. The model may be used to counsel patients and families on prognosis following aneurysmal SAH.

R2eD AVM Score.

Background and Purpose- The management of unruptured brain arteriovenous malformations remains unclear. Using a large cohort to determine risk factors predictive of hemorrhagic presentation of arteriovenous malformations, this study aims to develop a predictive tool that could guide hemorrhage risk stratification. Methods- A database of 789 arteriovenous malformation patients presenting to our institution between 1990 and 2017 was used. A hold-out method of model validation was used, whereby the data was randomly split in half into training and validation data sets. Factors significant at the univariable level in the training data set were used to construct a model based on multivariable logistic regression. Model performance was assessed using receiver operating curves on the training, validation, and complete data sets. The predictors and the complete data set were then used to derive a risk prediction formula and a practical scoring system, where every risk factor was worth 1 point except race, which was worth 2 points (total score varies from 0 to 6). The factors are summarized by R2eD arteriovenous malformation (acronym: R2eD AVM). Results- In 755 patients with complete data, 272 (36%) presented with hemorrhage. From the training data set, a model was derived containing the following risk factors: nonwhite race (odds ratio [OR]=1.8; P=0.02), small nidus size (OR=1.47; P=0.14), deep location (OR=2.3; P<0.01), single arterial feeder (OR=2.24; P<0.01), and exclusive deep venous drainage (OR=2.07; P=0.02). Area under the curve from receiver operating curve analysis was 0.702, 0.698, and 0.685 for the training, validation, and complete data sets, respectively. In the entire study population, the predicted probability of hemorrhagic presentation increased in a stepwise manner from 16% for patients with no risk factors (score of 0) to 78% for patients having all the risk factors (score of 6). Conclusions- The final model derived from this study can be used as a predictive tool that supplements clinical judgment and aids in patient counseling.

Ten-year analysis of saccular aneurysms in the Barrow Ruptured Aneurysm Trial.

OBJECTIVE: The authors present the 10-year results of the Barrow Ruptured Aneurysm Trial (BRAT) for saccular aneurysms. The 1-, 3-, and 6-year results of the trial have been previously reported, as have the 6-year results with respect to saccular aneurysms. This final report comparing the safety and efficacy of clipping versus coiling is limited to an analysis of those patients presenting with subarachnoid hemorrhage (SAH) from a ruptured saccular aneurysm. METHODS: In the study, 362 patients had saccular aneurysms and were randomized equally to the clipping and the coiling cohorts (181 each). The primary outcome analysis was based on the assigned treatment group; poor outcome was defined as a modified Rankin Scale (mRS) score > 2 and was independently adjudicated. The extent of aneurysm obliteration was adjudicated by a nontreating neuroradiologist. RESULTS: There was no statistically significant difference in poor outcome (mRS score > 2) or deaths between these 2 treatment arms during the 10 years of follow-up. Of 178 clip-assigned patients with saccular aneurysms, 1 (< 1%) was crossed over to coiling, and 64 (36%) of the 178 coil-assigned patients were crossed over to clipping. After the initial hospitalization, 2 of 241 (0.8%) clipped saccular aneurysms and 23 of 115 (20%) coiled saccular aneurysms required retreatment (p < 0.001). At the 10-year follow-up, 93% (50/54) of the clipped aneurysms were completely obliterated, compared with only 22% (5/23) of the coiled aneurysms (p < 0.001). Two patients had documented rebleeding, both died, and both were in the assigned and treated coiled cohort (2/83); no patient in the clipped cohort (0/175) died (p = 0.04). In 1 of these 2 patients, the hemorrhage was not from the target aneurysm but from an incidental basilar artery aneurysm, which was coiled at the same time. CONCLUSIONS: There was no significant difference in clinical outcomes between the 2 assigned treatment groups as measured by mRS outcomes or deaths. Clinical outcomes in the patients with posterior circulation aneurysms were better in the coiling group at 1 year, but after 1 year this difference was no longer statistically significant. Rates of complete aneurysm obliteration and rates of retreatment favored patients who actually underwent clipping compared with those who underwent coiling.Clinical trial registration no.: NCT01593267 (clinicaltrials.gov).

Indications for the Performance of Intracranial Endovascular Neurointerventional Procedures: A Scientific Statement From the American Heart Association.

Intracranial endovascular interventions provide effective and minimally invasive treatment of a broad spectrum of diseases. This area of expertise has continued to gain both wider application and greater depth as new and better techniques are developed and as landmark clinical studies are performed to guide their use. Some of the greatest advances since the last American Heart Association scientific statement on this topic have been made in the treatment of ischemic stroke from large intracranial vessel occlusion, with more effective devices and large randomized clinical trials showing striking therapeutic benefit. The treatment of cerebral aneurysms has also seen substantial evolution, increasing the number of aneurysms that can be treated successfully with minimally invasive therapy. Endovascular therapies for such other diseases as arteriovenous malformations, dural arteriovenous fistulas, idiopathic intracranial hypertension, venous thrombosis, and neoplasms continue to improve. The purpose of the present document is to review current information on the efficacy and safety of procedures used for intracranial endovascular interventional treatment of cerebrovascular diseases and to summarize key aspects of best practice.

Analysis of saccular aneurysms in the Barrow Ruptured Aneurysm Trial.

OBJECTIVE The Barrow Ruptured Aneurysm Trial (BRAT) is a prospective, randomized trial in which treatment with clipping was compared to treatment with coil embolization. Patients were randomized to treatment on presentation with any nontraumatic subarachnoid hemorrhage (SAH). Because all other randomized trials comparing these 2 types of treatments have been limited to saccular aneurysms, the authors analyzed the current BRAT data for this subgroup of lesions. METHODS The primary BRAT analysis included all sources of SAH: nonaneurysmal lesions; saccular, blister, fusiform, and dissecting aneurysms; and SAHs from an aneurysm associated with either an arteriovenous malformation or a fistula. In this post hoc review, the outcomes for the subgroup of patients with saccular aneurysms were further analyzed by type of treatment. The extent of aneurysm obliteration was adjudicated by an independent neuroradiologist not involved in treatment. RESULTS Of the 471 patients enrolled in the BRAT, 362 (77%) had an SAH from a saccular aneurysm. Patients with saccular aneurysms were assigned equally to the clipping and the coiling cohorts (181 each). In each cohort, 3 patients died before treatment and 178 were treated. Of the 178 clip-assigned patients with saccular aneurysms, 1 (1%) was crossed over to coiling, and 64 (36%) of the 178 coil-assigned patients were crossed over to clipping. There was no statistically significant difference in poor outcome (modified Rankin Scale score > 2) between these 2 treatment arms at any recorded time point during 6 years of follow-up. After the initial hospitalization, 1 of 241 (0.4%) clipped saccular aneurysms and 21 of 115 (18%) coiled saccular aneurysms required retreatment (p < 0.001). At the 6-year follow-up, 95% (95/100) of the clipped aneurysms were completely obliterated, compared with 40% (16/40) of the coiled aneurysms (p < 0.001). There was no difference in morbidity between the 2 treatment groups (p = 0.10). CONCLUSIONS In the subgroup of patients with saccular aneurysms enrolled in the BRAT, there was no significant difference between modified Rankin Scale outcomes at any follow-up time in patients with saccular aneurysms assigned to clipping compared with those assigned to coiling (intent-to-treat analysis). At the 6-year follow-up evaluation, rates of retreatment and complete aneurysm obliteration significantly favored patients who underwent clipping compared with those who underwent coiling. Clinical trial registration no.: NCT01593267 (clinicaltrials.gov).