Mediation of Successful Reperfusion Effect through Infarct Growth and Cerebral Edema: A Pooled, Patient-Level Analysis of EXTEND-IA Trials and SELECT Prospective Cohort.

OBJECTIVE: Reperfusion therapy is highly beneficial for ischemic stroke. Reduction in both infarct growth and edema are plausible mediators of clinical benefit with reperfusion. We aimed to quantify these mediators and their interrelationship. METHODS: In a pooled, patient-level analysis of the EXTEND-IA trials and SELECT study, we used a mediation analysis framework to quantify infarct growth and cerebral edema (midline shift) mediation effect on successful reperfusion (modified Treatment in Cerebral Ischemia ≥ 2b) association with functional outcome (modified Rankin Scale distribution). Furthermore, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift. RESULTS: A total 542 of 665 (81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful versus unsuccessful reperfusion. Median infarct growth was 12.3ml (interquartile range [IQR] = 1.8-48.4), and median midline shift was 0mm (IQR = 0-2.2). Of 249 (37%) demonstrating a midline shift of ≥1mm, median shift was 2.75mm (IQR = 1.89-4.21). Successful reperfusion was associated with reductions in both predefined mediators, infarct growth (ß = -1.19, 95% confidence interval [CI] = -1.51 to -0.88, p < 0.001) and midline shift (adjusted odds ratio = 0.36, 95% CI = 0.23-0.57, p < 0.001). Successful reperfusion association with improved functional outcome (adjusted common odds ratio [acOR] = 2.68, 95% CI = 1.86-3.88, p < 0.001) became insignificant (acOR = 1.39, 95% CI = 0.95-2.04, p = 0.094) when infarct growth and midline shift were added to the regression model. Infarct growth and midline shift explained 45% and 34% of successful reperfusion effect, respectively. Analysis considering an alternative hypothesis demonstrated consistent results. INTERPRETATION: In this mediation analysis from a pooled, patient-level cohort, a significant proportion (~80%) of successful reperfusion effect on functional outcome was mediated through reduction in infarct growth and cerebral edema. Further studies are required to confirm our findings, detect additional mediators to explain successful reperfusion residual effect, and identify novel therapeutic targets to further enhance reperfusion benefits. ANN NEUROL 2023;93:793-804.

Thrombectomy for Stroke With Large Infarct on Noncontrast CT: The TESLA Randomized Clinical Trial.

Importance: Recent large infarct thrombectomy trials used heterogeneous imaging modalities and time windows for patient selection. Noncontrast computed tomographic (CT) scan is the most common stroke imaging approach. It remains uncertain whether thrombectomy is effective for patients with large infarcts identified using noncontrast CT alone within 24 hours of stroke onset. Objective: To evaluate the effect of thrombectomy in patients with a large infarct on a noncontrast CT scan within 24 hours of onset. Design, Setting, and Participants: Open-label, blinded-end point, bayesian-adaptive randomized trial with interim analyses for early stopping (futility or success) or population enrichment, which was conducted at 47 US academic and community-based stroke thrombectomy centers. Three hundred patients presenting within 24 hours with anterior-circulation, large-vessel occlusion and large infarct on noncontrast CT scan, with Alberta Stroke Program Early CT Scores of 2 to 5, were randomized to undergo thrombectomy or usual care. Enrollment occurred July 16, 2019 to October 17, 2022; final follow-up, January 25, 2023. Intervention: The intervention patients (n = 152) underwent endovascular treatment using standard thrombectomy devices and usual medical care. Control patients (n = 148) underwent usual medical care alone. Main Outcomes and Measures: The primary efficacy end point was improvement in 90-day functional outcome measured using mean utility-weighted modified Rankin Scale (UW-mRS) scores (range, 0 [death or severe disability] to 10 [no symptoms]; minimum clinically important difference, 0.3). A bayesian model determined the posterior probability that the intervention would be superior to usual care; statistical significance was a 1-sided posterior probability of .975 or more. The primary adverse event end point was 90-day mortality; secondary adverse event end points included symptomatic intracranial hemorrhage and radiographic intracranial hemorrhage. Results: The trial enrolled 300 patients (152 intervention, 148 control; 138 females [46%]; median age, 67 years), without early stopping or enrichment; 297 patients completed the 90-day follow-up. The mean (SD) 90-day UW-mRS score was 2.93 (3.39) for the intervention group vs 2.27 (2.98) for the control group with an adjusted difference of 0.63 (95% credible interval [CrI], -0.09 to 1.34; posterior probability for superiority of thrombectomy, .96). The 90-day mortality was similar between groups: 35.3% (53 of 150) for the intervention group vs 33.3% (49 of 147) for the control group. Six of 151 patients (4.0%) in the intervention group and 2 of 149 (1.3%) in the control group experienced 24-hour symptomatic intracranial hemorrhage. Fourteen patients of 148 (9.5%) in the intervention group vs 4 of 146 (2.7%) in the control group experienced parenchymal hematoma type 1 hemorrhages; 14 (9.5%) in the intervention group vs 5 (3.4%) in the control group experienced parenchymal hematoma type 2 hemorrhages; and 24 (16.2%) in the intervention group vs 9 (6.2%) in the control group experienced subarachnoid hemorrhages. Conclusions and Relevance: Among patients with a large infarct on noncontrast CT within 24 hours, thrombectomy did not demonstrate improvement in functional outcomes. But the width of the credible interval around the effect estimate includes the possibility of both no important effect and a clinically relevant benefit, so the potential role of thrombectomy with this imaging approach and time window will likely require additional study. Trial Registration: ClinicalTrials.gov Identifier: NCT03805308.

Air pollution and stroke hospitalization in the Beibu Gulf Region of China: A case-crossover analysis.

BACKGROUND: The relationship between air pollution and stroke has been extensively studied, however, the evidence regarding the association between air pollution and hospitalization due to stroke and its subtypes in coastal areas of China is limited. OBJECTIVE: To estimate the associations between air pollution and hospitalizations of stroke and its subtypes in the Beibu Gulf Region of China. METHODS: We conducted a time-stratified case-crossover study in 15 cities in Beibu Gulf Region in China from 2013 to 2016. Exposures to PM1, PM2.5, PM10, SO2, NO2, O3, and CO on the case and control days were assessed at residential addresses using bilinear interpolation. Conditional logistic regressions were constructed to estimate city-specific associations adjusting for meteorological factors and public holidays. Meta-analysis was further conducted to pool all city-level estimates. RESULTS: There were 271,394 case days and 922,305 control days. The odds ratios (ORs) for stroke hospitalizations associated with each interquartile range (IQR) increase in 2-day averages of SO2 (IQR: 10.8 µg/m3), NO2 (IQR: 11.2 µg/m3), and PM10 (IQR: 37 µg/m3) were 1.047 (95 % CI [confidence interval]: 1.015-1.080), 1.040 (95 % CI: 1.027-1.053), and 1.018 (95 % CI: 1.004-1.033), respectively. The associations with hospitalizations of ischemic stroke were significant for all seven pollutants, while the association with hemorrhagic stroke was significant only for CO. The associations of SO2, NO2, and O3 with stroke hospitalization were significantly stronger in the cool season. CONCLUSIONS: Short-term increase in SO2, NO2, and PM10 might be important triggers of stroke hospitalization. All seven air pollutants were associated with ischemic stroke hospitalization, while only CO was associated with hemorrhagic stroke hospitalization. These results should be considered in public health policy.

Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT): A Prospective, Multicenter Cohort Study of Imaging Selection.

OBJECTIVE: The primary imaging modalities used to select patients for endovascular thrombectomy (EVT) are noncontrast computed tomography (CT) and CT perfusion (CTP). However, their relative utility is uncertain. We prospectively assessed CT and CTP concordance/discordance and correlated the imaging profiles on both with EVT treatment decisions and clinical outcomes. METHODS: A phase 2, multicenter, prospective cohort study of large-vessel occlusions presented up to 24 hours from last known well was conducted. Patients received a unified prespecified imaging evaluation (CT, CT angiography, and CTP with Rapid Processing of Perfusion and Diffusion software mismatch determination). The treatment decision, EVT versus medical management, was nonrandomized and at the treating physicians' discretion. An independent, blinded, neuroimaging core laboratory adjudicated favorable profiles based on predefined criteria (CT:Alberta Stroke Program Early CT Score ≥ 6, CTP:regional cerebral blood flow (<30%) < 70ml with mismatch ratio ≥ 1.2 and mismatch volume ≥ 10ml). RESULTS: Of 4,722 patients screened from January 2016 to February 2018, 361 patients were included. Two hundred eighty-five (79%) received EVT, of whom 87.0% had favorable CTs, 91% favorable CTPs, 81% both favorable profiles, 16% discordant, and 3% both unfavorable. Favorable profiles on the 2 modalities correlated similarly with 90-day functional independence rates (favorable CT = 56% vs favorable CTP = 57%, adjusted odds ratio [aOR] = 1.91, 95% confidence interval [CI] = 0.40-9.01, p = 0.41). Having a favorable profile on both modalities significantly increased the odds of receiving thrombectomy as compared to discordant profiles (aOR = 3.97, 95% CI = 1.97-8.01, p < 0.001). Fifty-eight percent of the patients with favorable profiles on both modalities achieved functional independence as compared to 38% in discordant profiles and 0% when both were unfavorable (p < 0.001 for trend). In favorable CT/unfavorable CTP profiles, EVT was associated with high symptomatic intracranial hemorrhage (sICH) (24%) and mortality (53%) rates. INTERPRETATION: Patients with favorable imaging profiles on both modalities had higher odds of receiving EVT and high functional independence rates. Patients with discordant profiles achieved reasonable functional independence rates, but those with an unfavorable CTP had higher adverse outcomes. Ann Neurol 2020;87:419-433.

Addressing Stroke Literacy in Nigeria Through Music: A Qualitative Study of Community Perspectives.

BACKGROUND: The incidence of stroke in Nigeria is unknown, but stroke literacy, defined here as awareness of stroke warning symptoms and risk factors may be poor in high-risk communities. Although there is growing recognition of the use of music as a conduit to promote health literacy, African music is often overlooked as a source of health information. We sought to understand community-level perspectives on using African music to promote acute stroke literacy. METHODS: A purposive sample of education, health and music professionals, high school and university students were recruited to participate in the qualitative study. Study participants completed a brainstorming exercise that elicited their perceptions of potential barriers and facilitators to the use of music to promote acute stroke literacy in Nigeria. Content analysis was used to identify key themes emerging from the brainstorming exercise. RESULTS: A total of 44 individuals, comprising of 25 students with a mean age of 15.9 ± 1.6 years (52% females) and 19 professionals with a mean age of 39 ± 7.7 years (57.9% males) participated in the brainstorming exercise. Facilitators to the use of music to promote acute stroke literacy in Nigeria include the cultural relevance of music, the ubiquity of music, and government involvement. Key barriers include religious beliefs that discourage the use of "secular" music, cost-related barriers, and limited government support. CONCLUSIONS: Findings from this study provide guidance aimed at improving acute stroke literacy in Nigeria, particularly the importance of government involvement in the development and implementation of stroke literacy interventions guided by African music. Future work should consider implementing interventions that leverage the cultural elements of African music and further assess the extent to which these identified facilitators and/or barriers may influence stroke literacy.

Call to Action: SARS-CoV-2 and CerebrovAscular DisordErs (CASCADE).

BACKGROUND AND PURPOSE: The novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), now named coronavirus disease 2019 (COVID-19), may change the risk of stroke through an enhanced systemic inflammatory response, hypercoagulable state, and endothelial damage in the cerebrovascular system. Moreover, due to the current pandemic, some countries have prioritized health resources towards COVID-19 management, making it more challenging to appropriately care for other potentially disabling and fatal diseases such as stroke. The aim of this study is to identify and describe changes in stroke epidemiological trends before, during, and after the COVID-19 pandemic. METHODS: This is an international, multicenter, hospital-based study on stroke incidence and outcomes during the COVID-19 pandemic. We will describe patterns in stroke management, stroke hospitalization rate, and stroke severity, subtype (ischemic/hemorrhagic), and outcomes (including in-hospital mortality) in 2020 during COVID-19 pandemic, comparing them with the corresponding data from 2018 and 2019, and subsequently 2021. We will also use an interrupted time series (ITS) analysis to assess the change in stroke hospitalization rates before, during, and after COVID-19, in each participating center. CONCLUSION: The proposed study will potentially enable us to better understand the changes in stroke care protocols, differential hospitalization rate, and severity of stroke, as it pertains to the COVID-19 pandemic. Ultimately, this will help guide clinical-based policies surrounding COVID-19 and other similar global pandemics to ensure that management of cerebrovascular comorbidity is appropriately prioritized during the global crisis. It will also guide public health guidelines for at-risk populations to reduce risks of complications from such comorbidities.

Site Experience and Outcomes in the Trevo Acute Ischemic Stroke (TRACK) Multicenter Registry.

Background and Purpose- It remains unclear how experience influences outcomes after the advent of stent retriever technology. We studied the relationship between site experience and outcomes in the Trevo Acute Ischemic Stroke multicenter registry. Methods- The 24 sites that enrolled patients in the Trevo Acute Ischemic Stroke registry were trichotomized into low-volume (<2 cases/month), medium-volume (2-4 cases/month), and high-volume centers (>4 cases/month). Baseline features, imaging, and clinical outcomes were compared across the 3 volume strata. A multivariable analysis was performed to assess whether outcomes were influenced by site volumes. Results- A total of 624 patients were included and distributed as low- (n=188 patients, 30.1%), medium- (n=175, 28.1%), and high-volume (n=261, 41.8%) centers. There were no significant differences in terms of age (mean, 66±16 versus 67±14 versus 65±15; P=0.2), baseline National Institutes of Health Stroke Scale (mean, 17.6±6.5 versus 16.8±6.5 versus 17.6±6.9; P=0.43), or occlusion site across the 3 groups. Median (interquartile range) times from stroke onset to groin puncture were 266 (181.8-442.5), 239 (175-389), and 336.5 (221.3-466.5) minutes in low-, medium-, and high-volume centers, respectively (P=0.004). Higher efficiency and better outcomes were seen in higher volume sites as demonstrated by shorter procedural times (median, 97 versus 67 versus 69 minutes; P<0.001), higher balloon guide catheter use (40% versus 36% versus 59%; P≤0.0001), and higher rates of good outcome (90-day modified Rankin Scale [mRS], ≤2; 39% versus 50% versus 53.4%; P=0.02). There were no appreciable differences in symptomatic intracranial hemorrhage or 90-day mortality. After adjustments in the multivariable analysis, there were significantly higher chances of achieving a good outcome in high- versus low-volume (odds ratio, 1.67; 95% CI, 1.03-2.7; P=0.04) and medium- versus low-volume (odds ratio, 1.75; 95% CI, 1.1-2.9; P=0.03) centers, but there were no significant differences between high- and medium-volume centers (P=0.86). Conclusions- Stroke center volumes significantly influence efficiency and outcomes in mechanical thrombectomy.

Stroke mimics under the drip-and-ship paradigm.

BACKGROUND: Recent reports suggested better outcomes associated with the drip-and-ship paradigm for acute ischemic stroke (AIS) treated with thrombolysis. We hypothesized that a higher rate of stroke mimics (SM) among AIS treated in nonspecialized stroke centers that are transferred to comprehensive centers is responsible for such outcomes. METHODS: Consecutive patients treated with thrombolysis according to the admission criteria were reviewed in a single comprehensive stroke center over 1 academic year (July 1, 2011 to June 30, 2012). Information on the basic demographic, hospital complications, psychiatric diagnoses, and discharge disposition was collected. We identified those patients who were treated at a facility and then transferred to the tertiary center (ie, drip-and-ship paradigm). In addition to comparative and adjusted analysis to identify predictors for SM, a stratified analysis by the drip-and-ship status was performed. RESULTS: One hundred twenty patients were treated with thrombolysis for AIS included in this analysis; 20 (16.7%) were discharged with the final diagnosis of SM; 14 of those had conversion syndrome and 6 patients had other syndromes (seizures, migraine, and hypoglycemia). Patients with SM were younger (55.6 ± 15.0 versus 69.4 ± 14.9, P = .0003) and more likely to harbor psychiatric diagnoses (45% versus 9%; P ≤ .0001). Eighteen of 20 SM patients (90%) had the drip-and-ship treatment paradigm compared with 65% of those with AIS (P = .02). None of the SM had hemorrhagic complications, and all were discharged to home. Predictors of SM on adjusted analysis included the drip-and-ship paradigm (odds ratio [OR] 12.8, 95% confidence interval [CI] 1.78, 92.1) and history of any psychiatric illness (OR 12.08; 95% CI 3.14, 46.4). Eighteen of 83 drip-and-ship patients (21.7%) were diagnosed with SM compared with 2 of 37 patients (5.4%) presented directly to the hub hospital (P = .02). CONCLUSION: The drip-and-ship paradigm and any psychiatric history predict the diagnosis of SM. None of the SM had thrombolysis-related complications, and all were discharged to home. These findings may explain the superior outcomes associated with the drip-and-ship paradigm in the treatment for AIS.

When Blood Cell Counts Matter: Hypereosinophilic Syndrome as a Rare Cause of Ischemic Strokes.

Hypereosinophilic syndrome (HES) is a rare condition characterized by elevated eosinophil counts (>1.5 x 109 on two consecutive measurements), which are of myeloid clonal in origin or are driven by excess cytokines. One subtype of HES exhibits the Fip1-like 1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRA) fusion gene, a gain-of-function mutation resulting in a hyperactive tyrosine kinase. HES, especially the FIP1L1-PDGFRA variant, exhibits an excellent response to chemotherapy with imatinib. In this report, we present a 38-year-old patient with no contributory past medical history who experienced sudden-onset fatigue, ataxia, visual changes, and headaches. He was found to have multiple small acute infarcts in his cerebrum and cerebellum. A stroke work-up, including transthoracic echocardiogram (TTE), transesophageal echocardiogram (TEE), and computed tomography angiography (CTA), did not yield insight into the origin of his infarcts. On CBC, he was consistently hypereosinophilic, and a bone marrow biopsy revealed hypercellularity and the FIP1L1-PDGFRA fusion gene, confirming the diagnosis of HES. The patient was treated first with methylprednisolone and then imatinib with excellent response. It appears that, in our patient, strokes were not of a thromboembolic nature but rather due to hypercoagulability. In this report, we advocate for considering HES and emphasize the importance of revisiting basic laboratory studies such as a CBC if the standard stroke workup fails to elucidate the mechanism behind ischemic strokes with an embolic pattern.

Optimizing prediction scores for poor outcome after intra-arterial therapy in anterior circulation acute ischemic stroke.

BACKGROUND AND PURPOSE: Intra-arterial therapy (IAT) promotes recanalization of large artery occlusions in acute ischemic stroke. Despite high recanalization rates, poor clinical outcomes are common. We attempted to optimize a score that combines clinical and imaging variables to more accurately predict poor outcome after IAT in anterior circulation occlusions. METHODS: Patients with acute ischemic stroke undergoing IAT at University of Texas (UT) Houston for large artery occlusions (middle cerebral artery or internal carotid artery) were reviewed. Independent predictors of poor outcome (modified Rankin Scale, 4-6) were studied. External validation was performed on IAT-treated patients at Emory University. RESULTS: A total of 163 patients were identified at UT Houston. Independent predictors of poor outcome (P≤0.2) were identified as score variables using sensitivity analysis and logistic regression. Houston Intra-Arterial Therapy 2 (HIAT2) score ranges 0 to 10: age (≤59=0, 60-79=2, ≥80 years=4), glucose (<150=0, ≥150=1), National Institute Health Stroke Scale (≤10=0, 11-20=1, ≥21=2), the Alberta Stroke Program Early CT Score (8-10=0, ≤7=3). Patients with HIAT2≥5 were more likely to have poor outcomes at discharge (odds ratio, 6.43; 95% confidence interval, 2.75-15.02; P<0.001). After adjusting for reperfusion (Thrombolysis in Cerebral Infarction score≥2b) and time from symptom onset to recanalization, HIAT2≥5 remained an independent predictor of poor outcome (odds ratio, 5.88; 95% confidence interval, 1.96-17.64; P=0.02). Results from the cohort of Emory (198 patients) were consistent; patients with HIAT2 score≥5 had 6× greater odds of poor outcome at discharge and at 90 days. HIAT2 outperformed other previously published predictive scores. CONCLUSIONS: The HIAT2 score, which combines clinical and imaging variables, performed better than all previous scores in predicting poor outcome after IAT for anterior circulation large artery occlusions.

Age-associated vasospasm in aneurysmal subarachnoid hemorrhage.

The relationship between age and vasospasm caused by subarachnoid hemorrhage (SAH) is controversial. We evaluated this relationship in a contemporary sample from a single institution. In a retrospective study design, we included patients with SAH caused by ruptured intracranial aneurysms. All patients underwent an evaluation that included head imaging, cerebral angiography, and treatment for the underlying aneurysm. Vasospasm was classified as absent, any vasospasm, or symptomatic vasospasm. Age was classified into 2 categories with a cutoff of 50 years, and also was stratified by decade. All patients had received preventative and therapeutic measures for vasospasm. Logistic regression analysis was used to assess the association between age and the occurrence of vasospasm. A total of 108 patients were included in this analysis, 67 of whom were age ≥50 years. The older patients had a higher incidence of vascular risk factors, and the younger patients had a higher incidence of smoking and illicit substance abuse. The mean age of the patients with any vasospasm (n = 41) was 48.51 ± 11.23 years, compared with 59.67 ± 13.30 years in those without vasospasm (P < .0001). Adjusted analysis found a greater risk of vasospasm in the younger patients compared with the older patients (odds ratio, 5.83; 95% confidence interval, 2.41-14.12 for any vasospasm; odds ratio, 2.66; 95% confidence interval, 1.008-7.052 for symptomatic vasospasm). This risk of vasospasm decreased with advanced age (P < .0001). Our findings suggest that patients age <50 years are at 5-fold greater risk of any vasospasm compared with older patients, and that age-adjusted prevention protocols may need to be considered.

Thrombectomy Outcomes With General vs Nongeneral Anesthesia: A Pooled Patient-Level Analysis From the EXTEND-IA Trials and SELECT Study.

BACKGROUND AND OBJECTIVES: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice. METHODS: In a pooled patient-level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II, and SELECT, EVT functional outcomes (modified Rankin Scale score distribution) were compared between general anesthesia (GA) vs non-GA in a propensity-matched sample. Furthermore, we evaluated the association of collateral flow on perfusion imaging, assessed by hypoperfusion intensity ratio (HIR) - Tmax > 10 seconds/Tmax > 6 seconds (good collaterals - HIR < 0.4, poor collaterals - HIR ≥ 0.4) on the association between anesthesia type and EVT outcomes. RESULTS: Of 725 treated with EVT, 299 (41%) received GA and 426 (59%) non-GA. The baseline characteristics differed in presentation National Institutes of Health Stroke Scale score (median [interquartile range] GA: 18 [13-22], non-GA: 16 [11-20], p < 0.001) and ischemic core volume (GA: 15.0 mL [3.2-38.0] vs non-GA: 9.0 mL [0.0-31.0], p < 0.001). In addition, GA was associated with longer last known well to arterial access (203 minutes [157-267] vs 186 minutes [138-252], p = 0.002), but similar procedural time (35.5 minutes [23-59] vs 34 minutes [22-54], p = 0.51). Of 182 matched pairs using propensity scores, baseline characteristics were similar. In the propensity score-matched pairs, GA was independently associated with worse functional outcomes (adjusted common odds ratio [adj. cOR]: 0.64, 95% CI: 0.44-0.93, p = 0.021) and higher neurologic worsening (GA: 14.9% vs non-GA: 8.9%, aOR: 2.10, 95% CI: 1.02-4.33, p = 0.045). Patients with poor collaterals had worse functional outcomes with GA (adj. cOR: 0.47, 95% CI: 0.29-0.76, p = 0.002), whereas no difference was observed in those with good collaterals (adj. cOR: 0.93, 95% CI: 0.50-1.74, p = 0.82), p interaction: 0.07. No difference was observed in infarct growth overall and in patients with good collaterals, whereas patients with poor collaterals demonstrated larger infarct growth with GA with a significant interaction between collaterals and anesthesia type on infarct growth rate (p interaction: 0.020). DISCUSSION: GA was associated with worse functional outcomes after EVT, particularly in patients with poor collaterals in a propensity score-matched analysis from a pooled patient-level cohort from 3 randomized trials and 1 prospective cohort study. The confounding by indication may persist despite the doubly robust nature of the analysis. These findings have implications for randomized trials of GA vs non-GA and may be of utility for clinicians when making anesthesia type choice. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that use of GA is associated with worse functional outcome in patients undergoing EVT. TRIAL REGISTRATION INFORMATION: EXTEND-IA: ClinicalTrials.gov (NCT01492725); EXTEND-IA TNK: ClinicalTrials.gov (NCT02388061); EXTEND-IA TNK part II: ClinicalTrials.gov (NCT03340493); and SELECT: ClinicalTrials.gov (NCT02446587).

Mortality of cerebral venous-sinus thrombosis in a large national sample.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the mortality rates associated with cerebral venous-sinus thrombosis in a large national sample. METHODS: A cohort of patients with cerebral venous-sinus thrombosis was identified from the National Inpatient Sample database for the years 2000 to 2007. According to the International Classification of Diseases, 9th Revision, Clinical Modification codes, cerebral venous-sinus thrombosis is categorized into pyogenic and nonpyogenic groups. Multivariate logistic regression analysis was used to assess covariates associated with hospital mortality. RESULTS: Among 3488 patients, the overall mortality rate was 4.39%, which was nonsignificantly higher among the pyogenic group (4.55% versus 3.52%; OR, 0.76; 95% CI, 0.47-1.23). In the pyogenic cerebral venous-sinus thrombosis group, hematologic disorders were the most frequent predisposing condition (16.2%); whereas systemic malignancy followed by hematologic disorders were most common in the nonpyogenic group (14.08% and 10.04%, respectively). Predictors of mortality included age, intracerebral hemorrhage as well as the predisposing conditions of hematologic disorders, systemic malignancy, and central nervous system infection. CONCLUSIONS: Compared with arterial stroke, CVST harbors a relatively low mortality rate. Death is determined by age, the presence of intracerebral hemorrhage, and certain predisposing conditions.

Proposed angiographic criteria for measurement of vertebral artery origin stenosis: the vertebral origin treatment with endovascular therapy (VOTE) method.

Standard measurement criteria for vertebral artery origin (VAO) stenosis have not yet been established. We propose such criteria and report on interrater agreement using two measurement methods in a series of patients referred for endovascular therapy. Three experienced angiography raters independently reviewed magnified cerebral angiograms. The formula [1 - (Ds/Dn)] × 100 was used, where Ds is the diameter of the most stenotic portion of the lesion and Dn is normal vessel diameter. The first measurement method allows unrestricted use of the V1 segment for measurement of normal diameter. In the second method, normal diameter is measured in the first portion of the V2 segment with exclusion of any region of poststenotic dilatation. Ten consecutive patients with VAO stenosis were reviewed. The mean degree of stenosis was 71.9% (standard deviation, ± 10.7%) with the first method and 66.9% ± 10.6% with the second method. Average interrater agreement was 80% with the first method and 87% with the second method. The intraclass correlation coefficient (ICC) demonstrated greater interrater agreement when the tortuous proximal V1 segment was excluded in normal diameter measurement (ICC = 0.7750) compared with the unrestricted use of the V1 segment for normal diameter (ICC = 0.7256). The kappa statistic was the best among the 3 raters with 10% variance when the tortuous V1 segment was excluded, at 0.73 (overall agreement, 87%). Our findings indicate that excluding the tortuous V1 portion when measuring normal diameter improves interrater agreement and simplifies the measurement of high-grade VAO stenosis.

Heparin-induced thrombocytopenia and cerebral venous sinus thrombosis: case report and literature review.

BACKGROUND: Heparin-induced thrombocytopenia (HIT)-related cerebral venous sinus thrombosis (CVST) has been described in 10 prior case reports in the English language medical literature. We report the first case of low molecular weight HIT-related CVST with detailed clinical course and novel therapeutic approach. METHODS: A 69-year-old woman presented with a focal seizure after total hip replacement. Enoxaparin for venous thromboembolism prophylaxis had been initiated 8 days prior to the seizure. RESULTS: The patient experienced progressive neurologic deterioration, and MRI and CT angiography were consistent with cerebral sinus thrombosis (CVST). The new onset of thrombocytopenia, thrombosis, and positive heparin ELISA (enzyme-linked immunosorbent assay) and SRA (serotonin release assay) assays confirmed HIT. In spite of aggressive management of HIT-related CVST, including argatroban therapy and endovascular mechanical thrombolysis, the patient expired. CONCLUSIONS: A review of the previous 10 case reports in the literature confirms that HIT-related CVST is often a fatal condition, particularly when diagnosed in comatose patients. Because the diagnosis is rare and often delayed relative to initial presentation, prevention is the key to improve patient outcomes. Newer anticoagulants with different mechanism of action than heparin are currently under review by the FDA; they will facilitate prevention of HIT-related CVST and other HIT-related neurological complications.

Vertebral artery origin stenosis and its treatment.

Vertebral artery origin stenosis (VAOS) is a common but underappreciated cause of stroke. It causes as many as 20% of posterior circulation stroke. This article reviews the epidemiology, natural history, and treatment of this condition. We focus on the emerging therapeutic endovascular options and their safety and durability. Finally, we discuss the gaps in the current understanding of VAOS and how best to explore them in the future.

Is thrombolysis safe in the elderly?: analysis of a national database.

BACKGROUND AND PURPOSE: Thrombolysis for acute ischemic stroke in the elderly population is seldom administered. METHODS: In this study, we evaluated the risks of thrombolysis, including the mortality and intracerebral hemorrhage (ICH) rates in this population. A cohort of patients was identified from the National Inpatient Sample database for the years 2000-2006. Age was categorized in 2 groups, including those between 18 and 80 years and those >80 years. Multivariate logistic regression analysis was used to assess covariates associated with hospital mortality and ICH. A total of 524 997 patients were admitted for acute ischemic stroke; 143 093 (27.2%) were >80 years. A total of 7950 patients were treated with thrombolysis, of which 1659 (20.9%) were >80 years. Elderly patients received less frequent thrombolysis compared with the younger population (1.05% versus 1.72%). RESULTS: In the whole cohort, the mortality rate was higher in the older population (12.80% versus 8.99%). For those treated with thrombolysis, the mortality rate and risk of ICH were higher among those >80 years (16.9% versus 11.5%; odds ratio: 1.56 [95% CI: 1.35 to 1.82] and 5.73% versus 4.40%; odds ratio: 1.31 [95% CI: 1.03 to 1.67], respectively). Multivariate logistic regression analysis showed that the presence of ICH (odds ratio: 2.24 [95% CI: 1.89 to 2.65]) was associated with higher mortality rates but not the use of thrombolysis (odds ratio: 1.14 [95% CI: 0.98 to 1.33]). CONCLUSIONS: Despite the higher mortality rate in the older population, the use of thrombolysis does not predict death; however, the use of thrombolysis was associated with high risk of ICH.

Hospital mortality and complications of electively clipped or coiled unruptured intracranial aneurysm.

BACKGROUND AND PURPOSE: To determine the hospital mortality rates associated with elective surgical clipping and endovascular coiling of unruptured intracranial aneurysms. METHODS: We identified a cohort of patients electively admitted to US hospitals with the diagnosis of unruptured intracranial aneurysm from the National Inpatient Sample database for the years 2000 through 2006. Patient demographics, hospital-associated complications, and in-hospital mortality were compared among the treatment groups. A multivariate logistic regression analysis was used to identify independent variables associated with hospital mortality. Cochrane-Armitage test was used to assess the trend of hospital use of these procedures. RESULTS: After data cleansing, 3738 (34.3%) patients had aneurysm clipping and 3498 (32.1%) had endovascular coiling. The basic demographics including age, race, and comorbidity indices were similar between the groups. The length of hospital stay was longer in the clipped population (median 4 versus 1 day; P<0.0001), incurring a higher hospital charge in the coiled population (median $42 070 versus $38 166; P<0.0001). Hospital mortality was higher in the clipped population: 60 (1.6%) versus 20 (0.57%; adjusted odds ratio 3.63; 95% CI, 1.57, 8.42). Perioperative intracerebral hemorrhage and acute ischemic stroke were higher in the clipped population. The rate of hospital use of the endovascular coiling has increased over the years included in this study (<0.0001). CONCLUSIONS: Elective coiling of unruptured intracranial aneurysms is associated with fewer deaths and perioperative complications compared with elective clipping. The trend of hospital use of the coiling procedures has increased during recent years.

Real-World Impact of Retrievable Stents for Acute Ischemic Stroke on Disability Utilizing the National Inpatient Sample.

PURPOSE: We assess the impact of retrievable stent (RS) compared to first-generation devices on in-hospital mortality and disability in patients with acute ischemic stroke (AIS). METHODS: Using the National Inpatient Sample, data were obtained for patients with a primary diagnosis of AIS who underwent mechanical thrombectomy (MT) and were admitted to US hospitals between 2010 and 2014. Two time periods were compared: 2010-2012 (pre-RS Food and Drug Administration [FDA] approval) and 2013-2014 (post-RS FDA approval). Disability level was used to classify outcomes as minimal disability, moderate to severe disability, or in-hospital mortality. Weighted, multivariable logistic regression was used to assess the association between MT device type and disability. RESULTS: A total of 2,443,713 weighted patients admitted with AIS were identified; 148,923 (4.9%) of these received intravenous tissue plasminogen activator; and 23,719 (0.8%) underwent MT. In multivariable logistic regression analysis, the odds of in-hospital mortality decreased (OR 0.69, 95% CI 0.59-0.82) in the post-RS time-period compared with pre-RS time. The odds of moderate-to-severe disability decreased (OR 0.88, 95% CI 0.73-1.06) compared with minimal disability. In-hospital mortality rates decreased successively over the 4 years in the MT-treated patients (p < 0.001). CONCLUSIONS: The FDA approval of RS technology after 2012 was associated with decreased in-hospital mortality when compared with the 3-year interval prior. These findings provide an indication that the RCT data on the efficacy of RS technology are translating into improved real-world outcomes.