Trial of Endovascular Thrombectomy for Large Ischemic Strokes.

BACKGROUND: Trials of the efficacy and safety of endovascular thrombectomy in patients with large ischemic strokes have been carried out in limited populations. METHODS: We performed a prospective, randomized, open-label, adaptive, international trial involving patients with stroke due to occlusion of the internal carotid artery or the first segment of the middle cerebral artery to assess endovascular thrombectomy within 24 hours after onset. Patients had a large ischemic-core volume, defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower scores indicating larger infarction) or a core volume of at least 50 ml on computed tomography perfusion or diffusion-weighted magnetic resonance imaging. Patients were assigned in a 1:1 ratio to endovascular thrombectomy plus medical care or to medical care alone. The primary outcome was the modified Rankin scale score at 90 days (range, 0 to 6, with higher scores indicating greater disability). Functional independence was a secondary outcome. RESULTS: The trial was stopped early for efficacy; 178 patients had been assigned to the thrombectomy group and 174 to the medical-care group. The generalized odds ratio for a shift in the distribution of modified Rankin scale scores toward better outcomes in favor of thrombectomy was 1.51 (95% confidence interval [CI], 1.20 to 1.89; P<0.001). A total of 20% of the patients in the thrombectomy group and 7% in the medical-care group had functional independence (relative risk, 2.97; 95% CI, 1.60 to 5.51). Mortality was similar in the two groups. In the thrombectomy group, arterial access-site complications occurred in 5 patients, dissection in 10, cerebral-vessel perforation in 7, and transient vasospasm in 11. Symptomatic intracranial hemorrhage occurred in 1 patient in the thrombectomy group and in 2 in the medical-care group. CONCLUSIONS: Among patients with large ischemic strokes, endovascular thrombectomy resulted in better functional outcomes than medical care but was associated with vascular complications. Cerebral hemorrhages were infrequent in both groups. (Funded by Stryker Neurovascular; SELECT2 ClinicalTrials.gov number, NCT03876457.).

Endovascular thrombectomy plus medical care versus medical care alone for large ischaemic stroke: 1-year outcomes of the SELECT2 trial.

BACKGROUND: Multiple randomised trials have shown efficacy and safety of endovascular thrombectomy in patients with large ischaemic stroke. The aim of this study was to evaluate long-term (ie, at 1 year) evidence of benefit of thrombectomy for these patients. METHODS: SELECT2 was a phase 3, open-label, international, randomised controlled trial with blinded endpoint assessment, conducted at 31 hospitals in the USA, Canada, Spain, Switzerland, Australia, and New Zealand. Patients aged 18-85 years with ischaemic stroke due to proximal occlusion of the internal carotid artery or of the first segment of the middle cerebral artery, showing large ischaemic core on non-contrast CT (Alberta Stroke Program Early Computed Tomographic Score of 3-5 [range 0-10, with lower values indicating larger infarctions]) or measuring 50 mL or more on CT perfusion and MRI, were randomly assigned, within 24 h of ischaemic stroke onset, to thrombectomy plus medical care or to medical care alone. The primary outcome for this analysis was the ordinal modified Rankin Scale (range 0-6, with higher scores indicating greater disability) at 1-year follow-up in an intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT03876457) and is completed. FINDINGS: The trial was terminated early for efficacy at the 90-day follow-up after 352 patients had been randomly assigned (178 to thrombectomy and 174 to medical care only) between Oct 11, 2019, and Sept 9, 2022. Thrombectomy significantly improved the 1-year modified Rankin Scale score distribution versus medical care alone (Wilcoxon-Mann-Whitney probability of superiority 0·59 [95% CI 0·53-0·64]; p=0·0019; generalised odds ratio 1·43 [95% CI 1·14-1·78]). At the 1-year follow-up, 77 (45%) of 170 patients receiving thrombectomy had died, compared with 83 (52%) of 159 patients receiving medical care only (1-year mortality relative risk 0·89 [95% CI 0·71-1·11]). INTERPRETATION: In patients with ischaemic stroke due to a proximal occlusion and large core, thrombectomy plus medical care provided a significant functional outcome benefit compared with medical care alone at 1-year follow-up. FUNDING: Stryker Neurovascular.

Anticoagulation Use and Endovascular Thrombectomy in Patients with Large Core Stroke: A Secondary Analysis of the SELECT2 Trial.

Endovascular thrombectomy (EVT) safety and efficacy in patients with large core infarcts receiving oral anticoagulants (OAC) are unknown. In the SELECT2 trial (NCT03876457), 29 of 180 (16%; vitamin K antagonists 15, direct OACs 14) EVT, and 18 of 172 (10%; vitamin K antagonists 3, direct OACs 15) medical management (MM) patients reported OAC use at baseline. EVT was not associated with better clinical outcomes in the OAC group (EVT 6 [4-6] vs MM 5 [4-6], adjusted generalized odds ratio 0.89 [0.53-1.50]), but demonstrated significantly better outcomes in patients without OAC (EVT 4 [3-6] vs MM 5 [4-6], adjusted generalized odds ratio 1.87 [1.45-2.40], p = 0.02). The OAC group had higher comorbidities, including atrial fibrillation (70% vs 17%), congestive heart failure (28% vs 10%), and hypertension (87% vs 72%), suggesting increased frailty. However, the results were consistent after adjustment for these comorbidities, and was similar regardless of the type of OACs used. Whereas any hemorrhage rates were higher in the OAC group receiving EVT (86% in OAC vs 70% in no OAC), no parenchymal hemorrhage or symptomatic intracranial hemorrhage were observed with OAC use in both the EVT and MM arms. Although we did not find evidence that the effect was due to excess hemorrhage or confounded by underlying cardiac disease or older age, OAC use alone should not exclude patients from receiving EVT. Baseline comorbidities and ischemic injury extent should be considered while making individualized treatment decisions. ANN NEUROL 2024.

Cervical Dissection in Patients With Tandem Lesions Is Associated With Distal Embolism and Lower Recanalization Success.

BACKGROUND: Tandem lesions consist of cervical internal carotid artery (ICA) stenosis or occlusion, most commonly of atherosclerosis or dissection etiology, plus a large vessel occlusion. In this study, we compare outcomes in patients with atherosclerosis versus dissection of the cervical ICA. METHODS: This multicenter retrospective cohort study includes data from tandem lesion patients who underwent endovascular treatment from 2015 to 2020. Atherosclerosis was defined as ICA stenosis/occlusion associated with a calcified lesion and dissection by the presence of a tapered or flame-shaped lesion and intramural hematoma. Primary outcome: 90-day functional independence (modified Rankin Scale score, 0-2); secondary outcomes: 90-day favorable shift in the modified Rankin Scale score, modified Thrombolysis in Cerebral Infarction score 2b-3, modified Thrombolysis in Cerebral Infarction score 2c-3, symptomatic intracranial hemorrhage, parenchymal hematoma type 2, petechial hemorrhage, distal embolization, early neurological improvement, and mortality. Analysis was performed with matching by inverse probability of treatment weighting. RESULTS: We included 526 patients (68 [59-76] years; 31% females); 11.2% presented dissection and 88.8%, atherosclerosis. Patients with dissection were younger, had lower rates of hypertension, hyperlipidemia, diabetes, and smoking history. They also exhibited higher rates of ICA occlusion, multiple stents (>1), and lower rates of carotid self-expanding stents. After matching and adjusting for covariates, there were no differences in 90-day functional independence. The rate of successful recanalization was significantly lower in the dissection group (adjusted odds ratio, 0.38 [95% CI, 0.16-0.91]; P=0.031), which also had significantly higher rates of distal emboli (adjusted odds ratio, 2.53 [95% CI, 1.15-5.55]; P=0.021). There were no differences in other outcomes. Acute ICA stenting seemed to increase the effect of atherosclerosis in successful recanalization. CONCLUSIONS: This study reveals that among patients with acute stroke with tandem lesions, cervical ICA dissection is associated with higher rates of distal embolism and lower rates of successful recanalization than atherosclerotic lesions. Using techniques to minimize the risk of distal embolism may mitigate this contrast. Further prospective randomized trials are warranted to fully understand these associations.

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.

A Systematic Review and Meta-Analysis of Drug Eluting Stents for Safety and Efficacy in Intracranial Atherosclerotic Disease.

BACKGROUND: Advancements in arterial stenting technology have challenged prior notions favoring medical management for intracranial atherosclerotic disease (ICAD). Where previous conclusions were drawn from bare metal stent (BMS) technology, recent studies suggest drug-eluting stents (DES) are favorable due to their anti-proliferative effect, which reduces vascular remodeling. METHODS: We conducted a systematic review and meta-analysis of the literature prior to August 2023 reviewing all reports of ICAD treated with DES. Our target outcomes were incidence of any stroke, transient ischemic attack (TIA), or death within 30 days (postprocedural complications), ischemic stroke in the territory of the qualifying artery beyond 30 days (long-term complications), radiographically detected in-stent restenosis rate (ISR), and symptomatic ISR during follow-up. A subgroup analysis further stratified preprocedural mean stenosis above and below 70% into severe and moderate cohorts, respectively. RESULTS: PubMed, Web of Science, Cochrane and EMBASE query identified 527 candidate articles, from which 14 studies met inclusion criteria for a total of 607 patients and 640 ICAD lesions. Incidence of postprocedural complications was 7.3% (95% CI 3.9-11.7%) with subgroup analysis demonstrating significantly higher incidence in the severely stenotic group [9.0% (95% CI 4.7-14.5%)] than the moderately stenotic group [3.0% (95% CI 0.7-6.8%)]. Long-term complications were 1.2% (95% CI 0.4-2.3%). Radiographic ISR was 3.5% (95% CI 1.4-6.3%) and symptomatic ISR was 0.3% (95% CI 0.0-1.5%). CONCLUSIONS: Our systematic review and meta-analysis suggest that DES can effectively reduce the risk of ISR and may be a viable treatment modality to reduce long-term complications in refractory ICAD patients.

Endovascular Thrombectomy for Large Ischemic Stroke Across Ischemic Injury and Penumbra Profiles.

Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain. Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect. Design, Setting, and Participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022. Intervention: EVT vs MM. Main Outcomes and Measures: Primary outcome was functional outcome-90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI. Results: Among 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled. Conclusion and Relevance: In this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.

Endovascular Thrombectomy Versus Medical Management in Isolated M2 Occlusions: Pooled Patient-Level Analysis from the EXTEND-IA Trials, INSPIRE, and SELECT Studies.

OBJECTIVE: The objective of this study was to evaluate functional and safety outcomes of endovascular thrombectomy (EVT) versus medical management (MM) in patients with M2 occlusion and examine their association with perfusion imaging mismatch and stroke severity. METHODS: In a pooled, patient-level analysis of 3 randomized controlled trials (EXTEND-IA, EXTEND-and IA-TNK parts 1 and 2) and 2 prospective nonrandomized studies (INSPIRE and SELECT), we evaluated EVT association with 90-day functional independence (modified Rankin Scale [mRS] = 0-2) in isolated M2 occlusions as compared to medical management overall and in subgroups by mismatch profile status and stroke severity. RESULTS: We included 517 patients (EVT = 195 and MM = 322), baseline median (interquartile range [IQR]) National Institutes of Health Stroke Scale (NIHSS) was 13 (8-19) in EVT versus 10 (6-15) in MM, p < 0.001. Pretreatment ischemic core did not differ (EVT = 10 [0-24] ml vs MM = 9 [3-21] ml, p = 0.59). Compared to MM, EVT was more frequently associated with functional independence (68.3 vs 61.6%, adjusted odds ratio [aOR] = 2.42, 95% confidence interval [CI] = 1.25-4.67, p = 0.008, inverse probability of treatment weights [IPTW]-OR = 1.75, 95% CI = 1.00-3.75, p = 0.05) with a shift toward better mRS outcomes (adjusted cOR = 2.02, 95% CI:1.23-3.29, p = 0.005), and lower mortality (5 vs 10%, aOR = 0.32, 95% CI = 0.12-0.87, p = 0.025). EVT was associated with higher functional independence in patients with a perfusion mismatch profile (EVT = 70.7% vs MM = 61.3%, aOR = 2.29, 95% CI = 1.09-4.79, p = 0.029, IPTW-OR = 2.02, 1.08-3.78, p = 0.029), whereas no difference was found in those without mismatch (EVT = 43.8% vs MM = 62.7%, p = 0.17, IPTW-OR: 0.71, 95% CI = 0.18-2.78, p = 0.62). Functional independence was more frequent with EVT in patients with moderate or severe strokes, as defined by baseline NIHSS above any thresholds from 6 to 10, whereas there was no difference between groups with milder strokes below these thresholds. INTERPRETATION: In patients with M2 occlusion, EVT was associated with improved clinical outcomes when compared to MM. This association was primarily observed in patients with a mismatch profile and those with higher stroke severity. ANN NEUROL 2022;91:629-639.

Thrombectomy versus Medical Management in Mild Strokes due to Large Vessel Occlusion: Exploratory Analysis from the EXTEND-IA Trials and a Pooled International Cohort.

OBJECTIVE: This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch. METHODS: The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial,  Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVTpri ) were compared to those who received primary MM (MMpri ), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)-matched cohorts. Patients were stratified by target mismatch (mismatch ratio ≥ 1.8 and mismatch volume ≥ 15ml). Primary outcome was functional independence (90-day modified Rankin Scale = 0-2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality). RESULTS: Of 540 patients, 286 (53%) received EVTpri and demonstrated larger critically hypoperfused tissue (Tmax > 6 seconds) volumes (median [IQR]: 64 [26-96] ml vs MMpri : 40 [14-76] ml, p < 0.001) and higher presentation NIHSS (median [IQR]: 4 [2-5] vs MMpri : 3 [2-4], p < 0.001). Functional independence was similar (EVTpri : 77.4% vs MMpri : 75.6%, adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 0.82-2.03, p = 0.27). EVT had worse safety regarding sICH (EVTpri : 16.3% vs MMpri : 1.3%, p < 0.001) and neurological worsening (EVTpri : 19.6% vs MMpri : 6.7%, p < 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVTpri : 77.4% vs MMpri : 72.7%, aOR = 1.68, 95% CI = 1.01-2.81, p = 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVTpri : 77.4% vs MMpri : 83.3%, aOR = 0.39, 95% CI = 0.12-1.34, p = 0.13) without target mismatch (pinteraction  = 0.06). Similar findings were observed in a propensity score-matched subpopulation. INTERPRETATION: Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022;92:364-378.

Dual-Stent retriever thrombectomy for extensive dural sinus thrombosis.

INTRODUCTION: First line treatment for cerebral venous thrombosis (CVT) is systemic anticoagulation. In cases with symptoms of elevated ICP, endovascular thrombectomy (EVT) is pursued. We describe two cases in which dual stent-retrievers were used for EVT. OBJECTIVES: The use of dual stent-retrievers has been described in arterial stroke when clot is present in the M1 artery and both M2 branches as a rescue therapy after 1 stent-retriever failed to remove the clot. We applied this same thinking to our EVT patients. METHODS: A 17-year-old female with imaging demonstrating occlusion of the superior sagittal sinus (SSS), dominant right transverse sinus (TS), right sigmoid sinus (SS), and upper right internal jugular vein (IJV). A 20-year-old female with a magnetic resonance venography (MRV) noting CVT in the dominant lateral left TS, SS, and upper left IJV. RESULTS: Both were taken for EVT due to severity of symptoms. Two 6 × 40 mm stent-retrievers were deployed into the CVT and then remove with continuous aspiration with significant recanalization. CONCLUSIONS: The average diameter of the dural sinuses is 8 mm compared to the average size of the middle cerebral artery 3-4 mm. The largest available SR in the United States is 6 mm, and the largest outer diameter of available aspiration catheters is 2-3 mm. Due to the larger size of the dural sinuses, using two SRs can result in more efficient recanalization and less radiation.

Takotsubo cardiomyopathy in the setting of a myasthenic crisis.

BACKGROUND: Myasthenic crisis is characterized by severe weakness in bulbar and respiratory muscles leading to respiratory failure and can be a natural result of myasthenia gravis or precipitate due to infections, surgeries, and pregnancy. It has been shown that stressful emotional events can lead to stress, or takotsubo cardiomyopathy. Takotsubo cardiomyopathy is characterized by transient reversible left ventricular dysfunction in the absence of obstructive artery disease with hypo- or akinesis of the apex with hypercontractility of the base. METHODS: Case report and review of literature. RESULTS: We report a 77-year old man with myasthenia gravis that was admitted to the neurological intensive care unit due to a myasthenic crisis. During the course of his treatment with plasma exchange, he developed hypotension with a reduced cardiac ejection fraction found on transthoracic electrocardiography. Repeat echocardiography 2 and 8 days later showed a normal ejection fraction and resolved cardiac function. CONCLUSION: While takotsubo cardiomyopathy rarely presents concurrently with a myasthenic crisis, its consideration is warranted in the face of cardiovascular decompensation. Given that several cardiac complications are known to be associated with myasthenic crisis, cardiac monitoring is advised. Nine reports describe takotsubo cardiomyopathy occurring concurrently with a myasthenic crisis; however, only one report demonstrates this association in the absence of concomitant comorbidities or significant emotional distress.

Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct.

BACKGROUND: The effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late thrombectomy. METHODS: We enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). The coprimary end points were the mean score for disability on the utility-weighted modified Rankin scale (which ranges from 0 [death] to 10 [no symptoms or disability]) and the rate of functional independence (a score of 0, 1, or 2 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating more severe disability) at 90 days. RESULTS: A total of 206 patients were enrolled; 107 were assigned to the thrombectomy group and 99 to the control group. At 31 months, enrollment in the trial was stopped because of the results of a prespecified interim analysis. The mean score on the utility-weighted modified Rankin scale at 90 days was 5.5 in the thrombectomy group as compared with 3.4 in the control group (adjusted difference [Bayesian analysis], 2.0 points; 95% credible interval, 1.1 to 3.0; posterior probability of superiority, >0.999), and the rate of functional independence at 90 days was 49% in the thrombectomy group as compared with 13% in the control group (adjusted difference, 33 percentage points; 95% credible interval, 24 to 44; posterior probability of superiority, >0.999). The rate of symptomatic intracranial hemorrhage did not differ significantly between the two groups (6% in the thrombectomy group and 3% in the control group, P=0.50), nor did 90-day mortality (19% and 18%, respectively; P=1.00). CONCLUSIONS: Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone. (Funded by Stryker Neurovascular; DAWN ClinicalTrials.gov number, NCT02142283 .).

Unique variant of idiopathic intracranial hypertension dural sinus stenting.

PURPOSE/AIM OF THE STUDY: To report on the successful treatment of idiopathic intracranial hypertension (IIH) in a patient with venous sinus stenosis secondary to a persistent occipital-marginal sinus (POMS) utilizing venous sinus stenting. MATERIALS/METHODS: A 55-year-old female presented with headaches and blurry vision. Ophthalmologic examination demonstrated papilledema. Two lumbar punctures demonstrated opening pressures of 31 and 38 cmH2O and provided temporary symptom relief. Cerebral venography demonstrated hypoplastic bilateral transverse-sigmoid sinuses with dominant drainage through a persistent occipital-marginal sinus (POMS). Multiple enlarged arachnoid granulations resulted in stenosis in the marginal sinus with an 18 mmHg mean pressure gradient across the stenosis. RESULTS: The decision was made for venous sinus stenting of the POMS. Immediate post-stenting venography demonstrated resolution of the POMS stenosis with flow only into the POMS and a mean pressure gradient across the stenosis normalized to 2 mmHg. Six-month follow-up venography demonstrated continued stent patency and clinical symptoms remained resolved. She has remained symptom free at 18 months. CONCLUSION: This writing summarizes the utility of endovascular dural sinus stenting and the importance of recognizing the dominant dural sinus drainage route in the treatment of IIH.

Risk of Intracranial Hemorrhage Following Intravenous tPA (Tissue-Type Plasminogen Activator) for Acute Stroke Is Low in Children.

Background and Purpose- Data regarding the safety and efficacy of intravenous tPA (tissue-type plasminogen activator) in childhood acute arterial ischemic stroke are inadequate. The TIPS trial (Thrombolysis in Pediatric Stroke; National Institutes of Health grant R01NS065848)-a prospective safety and dose-finding trial of intravenous tPA in acute childhood stroke-was closed for lack of accrual. TIPS sites have subsequently treated children with acute stroke in accordance with established institutional protocols supporting data collection on outcomes. Methods- Data on children treated with intravenous tPA for neuroimaging-confirmed arterial ischemic stroke were collected retrospectively from 16 former TIPS sites to establish preliminary safety data. Participating sites were required to report all children who were treated with intravenous tPA to minimize reporting bias. Symptomatic intracranial hemorrhage (SICH) was defined as ECASS (European Cooperative Acute Stroke Study) II parenchymal hematoma type 2 or any intracranial hemorrhage associated with neurological deterioration within 36 following tPA administration. A Bayesian beta-binomial model for risk of SICH following intravenous tPA was fit using a prior distribution based on the risk level in young adults (1.7%); to test for robustness, the model was also fit with uninformative and conservative priors. Results- Twenty-six children (age range, 1.1-17 years; median, 14 years; 12 boys) with stroke and a median pediatric National Institutes of Health Stroke Scale score of 14 were treated with intravenous tPA within 2 to 4.5 hours (median, 3.0 hours) after stroke onset. No patient had SICH. Two children developed epistaxis. Conclusions- The estimated risk of SICH after tPA in children is 2.1% (95% highest posterior density interval, 0.0%-6.7%; mode, 0.9%). Regardless of prior assumption, there is at least a 98% chance that the risk is <15% and at least a 93% chance that the risk is <10%. These results suggest that the overall risk of SICH after intravenous tPA in children with acute arterial ischemic stroke, when given within 4.5 hours after symptom onset, is low.

Intraarterial Thrombolysis as Rescue Therapy for Large Vessel Occlusions.

Background and Purpose- Mechanical thrombectomy (MT) devices have led to improved reperfusion and clinical outcomes in acute ischemic stroke patients with emergent large vessel occlusions; however, less than one-third of patients achieve complete reperfusion. Use of intraarterial thrombolysis in the context of MT may provide an opportunity to enhance these results. Here, we evaluate the use of intraarterial rtPA (recombinant tissue-type plasminogen activator) as rescue therapy (RT) after failed MT in the North American Solitaire Stent-Retriever Acute Stroke registry. Methods- The North American Solitaire Stent-Retriever Acute Stroke registry recruited sites within North America to submit data on acute ischemic stroke patients treated with the Solitaire device. After restricting the population of 354 patients to use of RT and anterior emergent large vessel occlusions, we compared patients who were treated with and without intraarterial rtPA after failed MT. Results- A total of 37 and 44 patients was in the intraarterial rtPA RT and the no intraarterial rtPA RT groups, respectively. Revascularization success (modified Thrombolysis in Cerebral Infarction ≥2b) was achieved in more intraarterial rtPA RT patients (61.2% versus 46.6%; P=0.13) with faster times to recanalization (100±85 versus 164±235 minutes; P=0.36) but was not statistically significant. The rate of symptomatic intracranial hemorrhage (13.9% versus 6.8%; P=0.29) and mortality (42.9% versus 44.7%; P=0.87) were similar between the groups. Good functional outcome (modified Rankin Scale score of ≤2) was numerically higher in intraarterial rtPA patients (22.9% versus 18.4%; P=0.64). Further restriction of the RT population to M1 occlusions only and time of onset to groin puncture ≤8 hours, resulted in significantly higher successful revascularization rates in the intraarterial rtPA RT cohort (77.8% versus 38.9%; P=0.02). Conclusions- Intraarterial rtPA as RT demonstrated a similar safety and clinical outcome profile, with higher reperfusion rates achieved in patients with M1 occlusions. Prospective studies are needed to delineate the role of intraarterial thrombolysis in MT.

First Pass Effect: A New Measure for Stroke Thrombectomy Devices.

BACKGROUND AND PURPOSE: In acute ischemic stroke, fast and complete recanalization of the occluded vessel is associated with improved outcomes. We describe a novel measure for newer generation devices: the first pass effect (FPE). FPE is defined as achieving a complete recanalization with a single thrombectomy device pass. METHODS: The North American Solitaire Acute Stroke Registry database was used to identify a FPE subgroup. Their baseline features and clinical outcomes were compared with non-FPE patients. Clinical outcome measures included 90-days modified Rankin Scale score, National Institutes of Health Stroke Scale score, mortality, and symptomatic intracranial hemorrhage. Multivariate analyses were performed to determine whether FPE independently resulted in improved outcomes and to identify predictors of FPE. RESULTS: A total of 354 acute ischemic stroke patients underwent thrombectomy in the North American Solitaire Acute Stroke registry. FPE was achieved in 89 out of 354 (25.1%). More middle cerebral artery occlusions (64% versus 52.5%) and fewer internal carotid artery occlusions (10.1% versus 27.7%) were present in the FPE group. Balloon guide catheters were used more frequently with FPE (64.0% versus 34.7%). Median time to revascularization was significantly faster in the FPE group (median 34 versus 60 minutes; P=0.0003). FPE was an independent predictor of good clinical outcome (modified Rankin Scale score ≤2 was seen in 61.3% in FPE versus 35.3% in non-FPE cohort; P=0.013; odds ratio, 1.7; 95% confidence interval, 1.1-2.7). The independent predictors of achieving FPE were use of balloon guide catheters and non-internal carotid artery terminus occlusion. CONCLUSIONS: The achievement of complete revascularization from a single Solitaire thrombectomy device pass (FPE) is associated with significantly higher rates of good clinical outcome. The FPE is more frequently associated with the use of balloon guide catheters and less likely to be achieved with internal carotid artery terminus occlusion.

Time Course of Flow-Mediated Dilation and Vascular Endothelial Growth Factor following Acute Stroke.

OBJECTIVES: People after stroke demonstrate alterations in vascular endothelial function measured by flow-mediated dilation. Limited information is available in the literature on possible protective factors following stroke. The aims of the secondary analysis were (1) to characterize the time course of vascular endothelial function using flow-mediated dilation at 72 hours after stroke and 1 week later during inpatient stroke rehabilitation and (2) to determine whether flow-mediated dilation was related to vascular endothelial growth factor, brain-derived neurotrophic factor, or estimated prestroke peak oxygen uptake. METHODS: Flow-mediated dilation using Doppler ultrasound was assessed in bilateral brachial arteries at the defined time points. Flow-mediated dilation and blood draws occurred on the same day between 7:30 am and 9:00 am following an overnight fast. Enzyme-linked immunosorbent assay was used to quantify plasma vascular endothelial growth factor and brain-derived neurotrophic factor values. A nonexercise estimate was used to calculate prestroke peak oxygen uptake. RESULTS: We have shown that between-limb differences are evident within 72 hours after stroke and remain 1 week later during inpatient rehabilitation. Higher values for vascular endothelial growth factor were associated with increased flow-mediated dilation at both time points. Higher estimated prestroke peak oxygen uptake was related to flow-mediated dilation. Brain-derived neurotrophic factor was not related to any outcome measures. CONCLUSIONS: Unique vascular adaptations start early after stroke in the stroke-affected limb and remain through inpatient stroke rehabilitation. Vascular endothelial growth factor and prestroke physical activity may have a protective role in vascular function following stroke. Future work should focus on mechanistic pathways for preservation of vascular health.

A case series of dural venous sinus stenting in idiopathic intracranial hypertension: association of outcomes with optical coherence tomography.

Purpose/Aim: Pseudotumor cerebri or idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure of unknown etiology. A subset of patients has shown benefit from endovascular dural venous sinus stenting (DVSS). We sought to identify a population of IIH patients who underwent DVSS to assess outcomes. MATERIALS AND METHODS: A retrospective study was performed to identify IIH patients with dural sinus stenosis treated with DVSS. Outcome measures included dural sinus pressure gradients, peripapillary retinal nerve fiber layer (RNFL) thickness using optical coherence tomography and improvement in symptoms. RESULTS: Seventeen patients underwent DVSS. Average pre- and post-intervention pressure gradients were 23.06 and 1.18 mmHg, respectively (p < 0.0001). Sixteen (94%) noted improvement in headache, fourteen (82%) had visual improvement and all (100%) patients had improved main symptom. Of 11 patients with optical coherence tomography, 8 showed decreased RNFL thickness and 3 remained stable; furthermore, these 11 patients had improved vision with improved papilledema in 8, lack of pre-existing papilledema in 2 and stable, mild edema in 1 patient. CONCLUSIONS: Our series of patients with dural sinus stenosis demonstrated improvement in vision and reduction in RNFL thickness. DVSS appears to be a useful treatment for IIH patients with dural sinus stenosis.

The relationship of pro-inflammatory markers to vascular endothelial function after acute stroke.

Purpose/Aim: Data from chronic stroke studies have reported reduced blood flow and vascular endothelial function in the stroke-affected limb. It is unclear whether these differences are present early after stroke. First, we investigated whether vascular endothelial function in the stroke-affected limb would be different from healthy adults. Second, we examined whether between-limb differences in vascular endothelial function existed in the stroke-affected arm compared to the non-affected arm. Last, we tested whether reduced vascular endothelial function was related to pro-inflammatory markers that are present early after stroke. MATERIALS AND METHODS: Vascular endothelial function was assessed by flow-mediated dilation (FMD) in the brachial artery within 72 h post-stroke. All participants withheld medications from midnight until after the procedure. Ultrasound scans and blood draws for pro-inflammatory markers occurred on the same day between 7:30 am and 9:00 am. RESULTS: People with acute stroke had significantly lower FMD (4.2% ± 4.6%) than control participants (8.5% ± 5.2%, p = 0.037). Stroke participants had between-limb differences in FMD (4.2% ± 4.6% stroke-affected vs. 5.3% ± 4.4% non-affected, p = 0.02), whereas, the control participants did not. Of the pro-inflammatory markers, only vascular cell adhesion molecule-1(VCAM-1) had a significant relationship to FMD (stroke-affected limb, r = -0.62, p = 0.03; non-affected limb, r = -0.75, p = 0.005), but not tumor necrosis factor alpha nor interleukin-6. CONCLUSIONS: Vascular endothelial function is reduced starting in the early stage of stroke recovery. People with higher levels of VCAM-1 had a lower FMD response.

Ambulatory Status Protects against Venous Thromboembolism in Acute Mild Ischemic Stroke Patients.

INTRODUCTION: Ischemic stroke patients are at high risk (up to 18%) for venous thromboembolism. We conducted a retrospective cross-sectional study to understand the predictors of acute postmild ischemic stroke patient's ambulatory status and its relationship with venous thromboembolism, hospital length of stay, and in-hospital mortality. METHODS: We identified 522 patients between February 2006 and May 2014 and collected data about patient demographics, admission NIHSS (National Institutes of Health Stroke Scale), venous thromboembolism prophylaxis, ambulatory status, diagnosis of venous thromboembolism, and hospital outcomes (length of stay, mortality). Chi-square test, t-test and Wilcoxon rank-sum test, and binary logistic regression were used for statistical analysis as appropriate. RESULTS: A total of 61 (11.7%), 48 (9.2%), and 23 (4.4%) mild ischemic stroke patients developed venous thromboembolism, deep venous thrombosis, and pulmonary embolism, respectively. During hospitalization, 281 (53.8%) patients were ambulatory. Independent predictors of in-hospital ambulation were being married (OR 1.64, 95% CI 1.10-2.49), being nonreligious (OR 2.19, 95% CI 1.34-3.62), admission NIHSS (per unit decrease in NIHSS; OR 1.62, 95% CI 1.39-1.91), and nonuse of mechanical venous thromboembolism prophylaxis (OR 1.62, 95% CI 1.02-2.61). After adjusting for confounders, ambulatory patients had lower rates of venous thromboembolism (OR .47, 95% CI .25-.89), deep venous thrombosis (OR .36, 95% CI .17-.73), prolonged length of hospital stay (OR .24, 95% CI .16-.37), and mortality (OR .43, 95% CI .21-.84). CONCLUSIONS: Our findings suggest that for hospitalized acute mild ischemic stroke patients, ambulatory status is an independent predictor of venous thromboembolism (specifically deep venous thrombosis), hospital length of stay, and in-hospital mortality.