Alex Abou-Chebl

Cooling for Acute Ischemic Brain Damage (COOL AID) An Open Pilot Study of Induced Hypothermia in Acute Ischemic Stroke

Background and Purpose— Hypothermia is effective in improving outcome in experimental models of brain infarction. We studied the feasibility and safety of hypothermia in patients with acute ischemic stroke treated with thrombolysis. Methods— An open study design was used. All patients presented with major ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score >15) within 6 hours of onset. After informed consent, patients with a persistent NIHSS score of >8 were treated with hypothermia to 32±1°C for 12 to 72 hours depending on vessel patency. All patients were monitored in the neurocritical care unit for complications. A modified Rankin Scale was measured at 90 days and compared with concurrent controls. Results— Ten patients with a mean age of 71.1±14.3 years and an NIHSS score of 19.8±3.3 were treated with hypothermia. Nine patients served as concurrent controls. The mean time from symptom onset to thrombolysis was 3.1±1.4 hours and from symptom onset to initiation of hypothermia was 6.2±1.3 hours. The mean duration of hypothermia was 47.4±20.4 hours. Target temperature was achieved in 3.5±1.5 hours. Noncritical complications in hypothermia patients included bradycardia (n=5), ventricular ectopy (n=3), hypotension (n=3), melena (n=2), fever after rewarming (n=3), and infections (n=4). Four patients with chronic atrial fibrillation developed rapid ventricular rate, which was noncritical in 2 and critical in 2 patients. Three patients had myocardial infarctions without sequelae. There were 3 deaths in patients undergoing hypothermia. The mean modified Rankin Scale score at 3 months in hypothermia patients was 3.1±2.3. Conclusion— Induced hypothermia appears feasible and safe in patients with acute ischemic stroke even after thrombolysis. Refinements of the cooling process, optimal target temperature, duration of therapy, and, most important, clinical efficacy, require further study.

Cooling for Acute Ischemic Brain Damage (COOL AID) A feasibility trial of endovascular cooling

Objective: To report results of a randomized pilot clinical feasibility trial of endovascular cooling in patients with ischemic stroke. Methods: Forty patients with ischemic stroke presenting within 12 hours of symptom onset were enrolled in the study. An endovascular cooling device was inserted into the inferior vena cava of those randomized to hypothermia. A core body temperature of 33 °C was targeted for 24 hours. All patients underwent clinical assessment and MRI initially, at days 3 to 5 and days 30 to 37. Results: Eighteen patients were randomized to hypothermia and 22 to receive standard medical management. Thirteen patients reached target temperature in a mean of 77 ± 44 minutes. Most tolerated hypothermia well. Clinical outcomes were similar in both groups. Mean diffusion-weighted imaging (DWI) lesion growth in the hypothermia group (n = 12) was 90.0 ± 83.5% compared with 108.4 ± 142.4% in the control group (n = 11) (NS). Mean DWI lesion growth in patients who cooled well (n = 8) was 72.9 ± 95.2% (NS). Conclusions: Induced moderate hypothermia is feasible using an endovascular cooling device in most patients with acute ischemic stroke. Further studies are needed to determine if hypothermia improves outcome.

Conscious Sedation Versus General Anesthesia During Endovascular Therapy for Acute Anterior Circulation Stroke: Preliminary Results From a Retrospective, Multicenter Study

Background and Purpose— Patients undergoing intra-arterial therapy (IAT) for acute ischemic stroke receive either general anesthesia (GA) or conscious sedation. GA may delay time to treatment, whereas conscious sedation may result in patient movement and compromise the safety of the procedure. We sought to determine whether there were differences in safety and outcomes in GA patients before initiation of IAT. Methods— A cohort of 980 patients at 12 stroke centers underwent IAT for acute stroke between 2005 and 2009. Only patients with anterior circulation strokes due to large-vessel occlusion were included in the study. A binary logistic-regression model was used to determine independent predictors of good outcome and death. Results— The mean age was 66±15 years and median National Institutes of Health Stroke Scale score was 17 (interquartile range, 13–20). The overall recanalization rate was 68% and the symptomatic hemorrhage rate was 9.2%. GA was used in 44% of patients with no differences in intracranial hemorrhage rates when compared with the conscious sedation group. The use of GA was associated with poorer neurologic outcome at 90 days (odds ratio=2.33; 95% CI, 1.63–3.44; P<0.0001) and higher mortality (odds ratio=1.68; 95% CI, 1.23–2.30; P<0.0001) compared with conscious sedation. Conclusions— Patients placed under GA during IAT for anterior circulation stroke appear to have a higher chance of poor neurologic outcome and mortality. There do not appear to be differences in hemorrhagic complications between the 2 groups. Future clinical trials with IAT can help elucidate the etiology of the differences in outcomes.

Imaging-Based Endovascular Therapy for Acute Ischemic Stroke due to Proximal Intracranial Anterior Circulation Occlusion Treated Beyond 8 Hours From Time Last Seen Well Retrospective Multicenter Analysis of 237 Consecutive Patients

Background and Purpose— Current selection criteria for intra-arterial therapies in the anterior circulation use time windows of 8 hours. Modern neuroimaging techniques have identified individuals with salvageable penumbra who present beyond this timeframe. We sought to assess safety, procedural, and clinical outcomes of MRI or CT perfusion imaging-based endovascular therapy in patients with anterior circulation stroke treated beyond 8 hours from time last seen well. Methods— We conducted a multicenter retrospective review of consecutive patients meeting the following criteria: (1) acute proximal intracranial anterior circulation occlusion; (2) endovascular treatment initiated >8 hours from time last seen well; and (3) treatment selection based on MRI or CT perfusion imaging. Results— Two hundred thirty-seven patients were identified (mean age, 63.8±16 years; mean baseline National Institutes of Health Stroke Scale, 15±5.5; mean time last seen well to treatment, 15±11.2 hours; male gender, 46%). Successful revascularization was achieved in 175 of 237 (73.84%) patients. Parenchymal hematoma occurred in 21 of 237 (8.86%) patients. The 90-day mortality rate was 21.5% (51 of 237). The rate of good outcomes was 45% (100 of 223) in the 223 patients with available modified Rankin Scale data at 90 days or time of hospital discharge. In multivariate analyses, age (OR, 0.96; 95% CI, 0.94 to 0.98; P=0.002), admission National Institutes of Health Stroke Scale (OR, 0.93; 0.87 to 0.98; P=0.016), and successful revascularization (OR, 4.32; 1.99 to 9.39; P<0.0001) were identified as independent predictors of good outcomes. Conclusions— Endovascular therapy can be instituted with acceptable safety beyond 8 hours from time last seen well when selection is based on advanced neuroimaging. Successful revascularization is significantly associated with higher rates of good outcomes. The benefit of this approach compared with standard medical therapy should be assessed in a prospective randomized trial.

Drug-Eluting Stents for the Treatment of Intracranial Atherosclerosis Initial Experience and Midterm Angiographic Follow-up

Background and Purpose— Intracranial stenting is associated with a 32% rate of restenosis. Drug-eluting stents (DES) have revolutionized the treatment of coronary artery disease and have greatly reduced the risk of in-stent stenosis. We present our experience with the feasibility and safety of using DES for patients with symptomatic intracranial atherosclerosis. Methods— All of the patients had >70% stenoses and had failed maximal medical therapy. They were pretreated with aspirin, clopidogrel, and intraprocedural heparin. All of the lesions were predilated, and balloons and stents were slightly undersized. Clopidogrel and aspirin were continued for 1 year, and patients had clinical follow-up and vascular imaging at 30 days, 6 months, and 1 year. Results— Eight patients with intracranial internal carotid artery (3), middle cerebral (2), basilar (2), and vertebral artery (1) stenoses were successfully treated with 4 Cypher (Cordis Corp) and 4 Taxus (Boston Scientific Inc) stents. The mean stenosis severity was reduced from 84.4%±10.2% to 2.5%±4.6%. One patient had an intraprocedural retinal embolism, but there were no other complications. Over a mean follow-up of 11.1±4.9 months (range, 2 to 17.3 months), patients have had repeat angiography (5) or transcranial Doppler with or without CT angiography (3). None of the patients have had clinical or significant angiographic restenosis or required target vessel revascularization. Conclusions— Elective intracranial stenting with DES appears to be feasible and safe, but additional clinical experience is required to assess its efficacy.

Balloon Guide Catheter Improves Revascularization and Clinical Outcomes With the Solitaire Device Analysis of the North American Solitaire Acute Stroke Registry

Background and Purpose— Efficient and timely recanalization is an important goal in acute stroke endovascular therapy. Several studies demonstrated improved recanalization and clinical outcomes with the stent retriever devices compared with the Merci device. The goal of this study was to evaluate the role of the balloon guide catheter (BGC) and recanalization success in a substudy of the North American Solitaire Acute Stroke (NASA) registry. Methods— The investigator-initiated NASA registry recruited 24 clinical sites within North America to submit demographic, clinical, site-adjudicated angiographic, and clinical outcome data on consecutive patients treated with the Solitaire Flow Restoration device. BGC use was at the discretion of the treating physicians. Results— There were 354 patients included in the NASA registry. BGC data were reported in 338 of 354 patients in this subanalysis, of which 149 (44%) had placement of a BGC. Mean age was 67.3±15.2 years, and median National Institutes of Health Stroke Scale score was 18. Patients with BGC had more hypertension (82.4% versus 72.5%; P=0.05), atrial fibrillation (50.3% versus 32.8%; P=0.001), and were more commonly administered tissue plasminogen activator (51.6% versus 38.8%; P=0.02) compared with patients without BGC. Time from symptom onset to groin puncture and number of passes were similar between the 2 groups. Procedure time was shorter in patients with BGC (120±28.5 versus 161±35.6 minutes; P=0.02), and less adjunctive therapy was used in patients with BGC (20% versus 28.6%; P=0.05). Thrombolysis in cerebral infarction 3 reperfusion scores were higher in patients with BGC (53.7% versus 32.5%; P<0.001). Distal emboli and emboli in new territory were similar between the 2 groups. Discharge National Institutes of Health Stroke Scale score (mean, 12±14.5 versus 17.5±16; P=0.002) and good clinical outcome at 3 months were superior in patients with BGC compared with patients without (51.6% versus 35.8%; P=0.02). Multivariate analysis demonstrated that the use of BGC was an independent predictor of good clinical outcome (odds ratio, 2.5; 95% confidence interval, 1.2–4.9). Conclusions— Use of a BGC with the Solitaire Flow Restoration device resulted in superior revascularization results, faster procedure times, decreased need for adjunctive therapy, and improved clinical outcome.

Endovascular Treatment of Acute Ischemic Stroke May Be Safely Performed With No Time Window Limit in Appropriately Selected Patients

Background and Purpose— The traditional time window for acute ischemic stroke intra-arterial therapy (IAT) is <6 hours, which is based on pharmacological thrombolysis without penumbral imaging. This study was conducted to determine the safety of patient selection for IAT based on perfusion mismatch rather than time. Methods— A cohort of consecutive patients treated with IAT was identified by database review. Patients were selected for IAT based on the presence of perfusion mismatch using CT perfusion or MRI regardless of stroke duration. Thrombolytics were minimized after 6 hours in favor of mechanical embolectomy or angioplasty±stenting. Outcomes (National Institutes of Health Stroke Scale, modified Rankin Scale) were assessed by independent examiners. A multivariate analysis was performed to compare those treated <6 hours (early) with those treated >6 hours (late). Results— Fifty-five patients (mean National Institutes of Health Stroke Scale=19.7±5.7) were treated, 34 early and 21 late, with mean time-to-intervention of 3.4±1.6 hours and 18.6±16.0 hours, respectively. Thrombolysis In Myocardial Ischemia 2 or 3 recanalization was achieved in 82.8% early and 85.7% late patients (P=1.0). Intracerebral hemorrhage occurred in 25.5% overall, but symptomatic intracerebral hemorrhage occurred in 8.8% of the early and 9.5% of the late patients (P=1.0). Thirty-day mortality was similar (29.4% versus 23.8%, P=0.650). At 3 months, 41.2% and 42.9%, respectively, achieved a modified Rankin Scale ≤2 (P=0.902). Only presenting National Institutes of Health Stroke Scale was a predictor of modified Rankin Scale ≤2 (OR 0.794[95% CI 0.68 to 0.92], P=0.009) and death (adjusted OR 1.29[95% CI 1.04 to 1.59], P=0.019). Conclusions— In appropriately selected patients, IAT for acute ischemic stroke can be performed safely regardless of stroke duration. The concept of an acute ischemic stroke treatment window for IAT should be re-evaluated with a clinical trial selecting patients with perfusion mismatch.

Multimodal Therapy for the Treatment of Severe Ischemic Stroke Combining GPIIb/IIIa Antagonists and Angioplasty After Failure of Thrombolysis

Background and Purpose— Intraarterial and intravenous thrombolysis are often ineffective for the treatment of acute ischemic stroke and are associated with a significant risk of intracranial hemorrhage (ICH). Multimodal rescue therapy combining mechanical disruption and platelet GPIIb/IIIa receptor antagonists may improve recanalization. Methods— Patients who did not recanalize with thrombolysis were treated with GPIIb/IIIa antagonists, angioplasty, or an embolectomy device. Treatment was individualized based on vascular anatomy, stroke mechanism, patient status, and symptom duration. Results— Twelve patients were treated within 3.8±2.2 hours. The mean National Institutes of Health Stroke Scale (NIHSS) score was 19.4±4.1. Six patients had carotid terminus occlusion, whereas 5 had middle cerebral artery and 1 had basilar artery occlusion. The average doses of intraarterial tPA and reteplase were 17.1±8.6 mg and 2±0.6 units, respectively. All patients received either an intravenous or intraarterial abciximab bolus (mean 11.8±5.8mg) and heparin (mean 3278±1716U). Eleven were treated with angioplasty and 4 had mechanical embolectomy or stenting. Complete (8) or partial (3) recanalization was achieved in 11 cases. There was only one (8.3%) symptomatic hemorrhage. Patients had a favorable outcome at discharge (mean NIHSS 8.9±8.7) and 6 (50%) had an NIHSS ≤4 at discharge. Conclusions— Multimodal rescue therapy was effective at recanalizing occluded cerebral vessels that failed thrombolysis without an excess risk of ICH.

Intensive treatment of hypertension decreases the risk of hyperperfusion and intracerebral hemorrhage following carotid artery stenting

Objectives: To assess the efficacy of a comprehensive blood pressure (BP) management protocol in reducing intracerebral hemorrhage (ICH) following carotid artery stenting (CAS). Background: Following CAS hyperperfusion syndrome (HPS) can lead to significant morbidity and mortality. Hypertension plays an essential role in its development. Methods:We instituted a comprehensive BP protocol following the last case of ICH complicating a CAS procedure. All patients received comprehensive monitoring of BP and treatment to a BP < 140/90 mm Hg; those with a treated stenosis ≥90%, contralateral stenosis ≥80%, and hypertension (i.e., risk factors for HPS) were treated to a BP < 120/80 mm Hg. Patients who developed HPS received parenteral β‐blockers or nitrates titrated to resolution of symptoms and discharged when asymptomatic and normotensive. Patients and families were instructed to measure BP twice daily for 2 weeks and to call if hypertension or headache developed. Results: A total of 836 patients had CAS, 266 prior to the comprehensive BP management program and 570 subsequently. The incidence of HPS/ICH was 5/266 (1.9%) patients prior to comprehensive BP management and 3/570 (0.5%) patients afterwards, P = 0.12. The incidence of ICH was 3/266 (1.1%) and 0/570, respectively, P = 0.032. In high‐risk patients both HPS and ICH were significantly reduced from 29.4 to 4.2% (P = 0.006) and 17.6–0% (P = 0.006), respectively. There were no complications attributable to the comprehensive program and lengths of hospitalization were similar (2.6 vs. 2.1 days, P = 0.18). Conclusions: Comprehensive management of arterial hypertension can lower the incidence of ICH and HPS in high‐risk patients following CAS, without additional complications or prolonged hospitalizations.

North American Solitaire Stent Retriever Acute Stroke registry: post-marketing revascularization and clinical outcome results

Background Limited post-marketing data exist on the use of the Solitaire FR device in clinical practice. The North American Solitaire Stent Retriever Acute Stroke (NASA) registry aimed to assess the real world performance of the Solitaire FR device in contrast with the results from the SWIFT (Solitaire with the Intention for Thrombectomy) and TREVO 2 (Trevo versus Merci retrievers for thrombectomy revascularization of large vessel occlusions in acute ischemic stroke) trials. Methods The investigator initiated NASA registry recruited North American sites to submit retrospective angiographic and clinical outcome data on consecutive acute ischemic stroke (AIS) patients treated with the Solitaire FR between March 2012 and February 2013. The primary outcome was a Thrombolysis in Myocardial Ischemia (TIMI) score of ≥2 or a Treatment in Cerebral Infarction (TICI) score of ≥2a. Secondary outcomes were 90 day modified Rankin Scale (mRS) score, mortality, and symptomatic intracranial hemorrhage. Results 354 patients underwent treatment for AIS using the Solitaire FR device in 24 centers. Mean time from onset to groin puncture was 363.4±239 min, mean fluoroscopy time was 32.9±25.7 min, and mean procedure time was 100.9±57.8 min. Recanalization outcome: TIMI ≥2 rate of 83.3% (315/354) and TICI ≥2a rate of 87.5% (310/354) compared with the operator reported TIMI ≥2 rate of 83% in SWIFT and TICI ≥2a rate of 85% in TREVO 2. Clinical outcome: 42% (132/315) of NASA patients demonstrated a 90 day mRS ≤2 compared with 37% (SWIFT) and 40% (TREVO 2). 90 day mortality was 30.2% (95/315) versus 17.2% (SWIFT) and 29% (TREVO 2). Conclusions The NASA registry demonstrated that the Solitaire FR device performance in clinical practice is comparable with the SWIFT and TREVO 2 trial results.