Gene Sung

Safety and Efficacy of Mechanical Embolectomy in Acute Ischemic Stroke Results of the MERCI Trial

Background and Purpose— The only Food and Drug Administration (FDA)-approved treatment for acute ischemic stroke is tissue plasminogen activator (tPA) given intravenously within 3 hours of symptom onset. An alternative strategy for opening intracranial vessels during stroke is mechanical embolectomy, especially for patients ineligible for intravenous tPA. Methods— We investigated the safety and efficacy of a novel embolectomy device (Merci Retriever) to open occluded intracranial large vessels within 8 hours of the onset of stroke symptoms in a prospective, nonrandomized, multicenter trial. All patients were ineligible for intravenous tPA. Primary outcomes were recanalization and safety, and secondary outcomes were neurological outcome at 90 days in recanalized versus nonrecanalized patients. Results— Recanalization was achieved in 46% (69/151) of patients on intention to treat analysis, and in 48% (68/141) of patients in whom the device was deployed. This rate is significantly higher than that expected using an historical control of 18% (P<0.0001). Clinically significant procedural complications occurred in 10 of 141 (7.1%) patients. Symptomatic intracranial hemorrhages was observed in 11 of 141 (7.8%) patients. Good neurological outcomes (modified Rankin score ≤2) were more frequent at 90 days in patients with successful recanalization compared with patients with unsuccessful recanalization (46% versus 10%; relative risk [RR], 4.4; 95% CI, 2.1 to 9.3; P<0.0001), and mortality was less (32% versus 54%; RR, 0.59; 95% CI, 0.39 to 0.89; P=0.01). Conclusions— A novel endovascular embolectomy device can significantly restore vascular patency during acute ischemic stroke within 8 hours of stroke symptom onset and provides an alternative intervention for patients who are otherwise ineligible for thrombolytics.

Mechanical Thrombectomy for Acute Ischemic Stroke Final Results of the Multi MERCI Trial

Background and Purpose— Endovascular mechanical thrombectomy may be used during acute ischemic stroke due to large vessel intracranial occlusion. First-generation MERCI devices achieved recanalization rates of 48% and, when coupled with intraarterial thrombolytic drugs, recanalization rates of 60% have been reported. Enhancements in embolectomy device design may improve recanalization rates. Methods— Multi MERCI was an international, multicenter, prospective, single-arm trial of thrombectomy in patients with large vessel stroke treated within 8 hours of symptom onset. Patients with persistent large vessel occlusion after IV tissue plasminogen activator treatment were included. Once the newer generation (L5 Retriever) device became available, investigators were instructed to use the L5 Retriever to open vessels and could subsequently use older generation devices and/or intraarterial tissue plasminogen activator. Primary outcome was recanalization of the target vessel. Results— One hundred sixty-four patients received thrombectomy and 131 were initially treated with the L5 Retriever. Mean age±SD was 68±16 years, and baseline median (interquartile range) National Institutes of Health Stroke Scale score was 19 (15 to 23). Treatment with the L5 Retriever resulted in successful recanalization in 75 of 131 (57.3%) treatable vessels and in 91 of 131 (69.5%) after adjunctive therapy (intraarterial tissue plasminogen activator, mechanical). Overall, favorable clinical outcomes (modified Rankin Scale 0 to 2) occurred in 36% and mortality was 34%; both outcomes were significantly related to vascular recanalization. Symptomatic intracerebral hemorrhage occurred in 16 patients (9.8%); 4 (2.4%) of these were parenchymal hematoma type II. Clinically significant procedural complications occurred in 9 (5.5%) patients. Conclusions— Higher rates of recanalization were associated with a newer generation thrombectomy device compared with first-generation devices, but these differences did not achieve statistical significance. Mortality trended lower and the proportion of good clinical outcomes trended higher, consistent with better recanalization.

Complex partial status epilepticus accompanied by serious morbidity and mortality

Nonconvulsive status epilepticus (NCSE) accounts for approximately 20% of all status epilepticus (SE).Although convulsive SE is recognized as a medical emergency, prompt diagnosis and treatment of patients with NCSE is often not emphasized because its consequences are thought to be benign. We report 10 patients with persistent neurologic deficits or death after well-documented NCSE in the form of complex partial status epilepticus (CPSE). All patients had prolonged CPSE lasting 36 hours or longer, as documented by clinical and EEG findings. Causes for CPSE were preexisting epilepsy with partial and secondarily generalized seizures (3 patients), vascular disease (2 patients), encephalitis (2 patients), and metabolic disease (1 patient); causes were unknown for two patients. Poor outcomes identified included persistent (lasting at least 3 months) or permanent cognitive or memory loss (5 patients), cognitive or memory loss plus motor and sensory dysfunction (3 patients), and death (3 patients). NCSE in the form of CPSE is not a benign entity. Serious morbidity and mortality may occur due to the adverse effects of prolonged seizures and as a result of acute brain disorders that precipitate the seizures. NEUROLOGY 1995;45: 1499-1504

Predictors of Good Clinical Outcomes, Mortality, and Successful Revascularization in Patients With Acute Ischemic Stroke Undergoing Thrombectomy: Pooled Analysis of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI Trials

Background and Purpose— The Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials evaluated the safety and efficacy of thrombectomy in the treatment of intracranial arterial occlusions within 8 hours of symptom onset. We sought to determine the predictors of clinical and angiographic outcomes in these patients. Methods— The trial cohorts were combined in a data set of 305 patients. Twenty-eight baseline variables were included in univariate and multivariate analyses to define the independent predictors of good outcomes (modified Rankin Scale score ≤2), mortality, and successful revascularization (Thrombolysis In Myocardial Ischemia 2 to 3 flow). Results— In the univariate analysis, final revascularization, baseline National Institutes of Health Stroke Scale, age, and systolic blood pressure were associated with both good outcomes and mortality at 90 days (P<0.0018 for all). In the multivariate analysis, final revascularization (OR, 20.4; 95% CI, 7.7 to 53.9; P<0.0001), baseline National Institutes of Health Stroke Scale (OR, 0.86; 95% CI, 0.81 to 0.92; P<0.0001), and age (OR, 0.96; 95% CI, 0.95 to 0.98; P=0.0004) were independent predictors of good outcome. Final revascularization (OR, 0.28; 95% CI, 0.16 to 0.50; P<0.0001), baseline National Institutes of Health Stroke Scale score (odds ratio, 1.09; 95% CI, 1.04 to 1.14; P=0.0001), age (OR, 1.05; 95% CI, 1.03 to 1.07; P<0.0001), and internal carotid artery occlusion (OR, 2.17; 95% CI, 1.22 to 3.86; P=0.0084) were the strongest predictors of mortality. Systolic blood pressure (<150 versus ≥150 mm Hg; OR, 0.42; 95% CI, 0.26 to 0.70; P=0.0007) and M2 occlusion (OR, 3.86; 95% CI, 1.28 to 11.67; P=0.0168) were independent predictors of revascularization. Conclusion— Final recanalization status represents the strongest predictor of clinical outcomes in patients undergoing thrombectomy. The ability to remove the clot is negatively influenced by systolic blood pressure on presentation perhaps because of the hydraulic forces imposed by higher blood pressures. Although internal carotid artery occlusions are associated with increased mortality, they do not appear to influence the chances of good outcomes. This finding supports the inclusion of internal carotid artery occlusions in future efficacy trials.

Prehospital use of magnesium sulfate as neuroprotection in acute stroke.

BACKGROUND Magnesium sulfate is neuroprotective in preclinical models of stroke and has shown signals of potential efficacy with an acceptable safety profile when delivered early after stroke onset in humans. Delayed initiation of neuroprotective agents has hindered earlier phase 3 trials of neuroprotective agents. METHODS We randomly assigned patients with suspected stroke to receive either intravenous magnesium sulfate or placebo, beginning within 2 hours after symptom onset. A loading dose was initiated by paramedics before the patient arrived at the hospital, and a 24-hour maintenance infusion was started on the patients arrival at the hospital. The primary outcome was the degree of disability at 90 days, as measured by scores on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability). RESULTS Among the 1700 enrolled patients (857 in the magnesium group and 843 in the placebo group), the mean (±SD) age was 69±13 years, 42.6% were women, and the mean pretreatment score on the Los Angeles Motor Scale of stroke severity (range, 0 to 10, with higher scores indicating greater motor deficits) was 3.7±1.3. The final diagnosis of the qualifying event was cerebral ischemia in 73.3% of patients, intracranial hemorrhage in 22.8%, and a stroke-mimicking condition in 3.9%. The median interval between the time the patient was last known to be free of stroke symptoms and the start of the study-drug infusion was 45 minutes (interquartile range, 35 to 62), and 74.3% of patients received the study-drug infusion within the first hour after symptom onset. There was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the magnesium group and those in the placebo group (P=0.28 by the Cochran-Mantel-Haenszel test); mean scores at 90 days did not differ between the magnesium group and the placebo group (2.7 in each group, P=1.00). No significant between-group differences were noted with respect to mortality (15.4% in the magnesium group and 15.5% in the placebo group, P=0.95) or all serious adverse events. CONCLUSIONS Prehospital initiation of magnesium sulfate therapy was safe and allowed the start of therapy within 2 hours after the onset of stroke symptoms, but it did not improve disability outcomes at 90 days. (Funded by the National Institute of Neurological Disorders and Stroke; FAST-MAG ClinicalTrials.gov number, NCT00059332.).

Prognostic significance of hypernatremia and hyponatremia among patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE Abnormal serum sodium levels (hyponatremia and hypernatremia) are frequently observed during the acute period after aneurysmal subarachnoid hemorrhage (SAH) and may worsen cerebral edema and mass effect. We performed this study to determine the prognostic significance of serum sodium concentration abnormalities. METHODS We analyzed prospectively collected data for the placebo treatment group in a clinical trial conducted at 54 neurosurgical centers in North America. The presence of hypernatremia (serum sodium concentration of >145 mmol/L) and hyponatremia (serum sodium concentration of <135 mmol/L) was determined with serum sodium measurements obtained at admission and 3, 6, and 9 days after SAH. The effects of hypernatremia and hyponatremia on the risk of symptomatic vasospasm and on 3-month outcomes were analyzed after adjustment for the following potential confounding factors: age, sex, preexisting hypertension, admission Glasgow Coma Scale score, initial mean arterial pressure, subarachnoid clot thickness, intraventricular blood or intraparenchymal hematoma, ventricular dilation, and aneurysm size and location. RESULTS Of 298 patients in the analysis, 58 (19%) developed hypernatremia and 88 (30%) developed hyponatremia. Hypernatremia was significantly associated with poor outcomes (odds ratio, 2.7; 95% confidence interval, 1.2–6.1). A positive correlation was observed between the highest sodium values recorded and Glasgow Outcome Scale scores at 3 months (P < 0.0001 by analysis of variance). Hyponatremia was not associated with 3-month outcomes (odds ratio, 1.9; 95% confidence interval, 0.9–4.3). Neither hypernatremia nor hyponatremia was associated with the risk of symptomatic vasospasm. CONCLUSION Hyponatremia seems to be more common than hypernatremia after SAH. However, hypernatremia after SAH is independently associated with poor outcomes, and this association is independent of previously identified outcome predictors, including age and admission Glasgow Coma Scale scores. Further studies are needed to define the underlying mechanism of this association.

Metrics for Measuring Quality of Care in Comprehensive Stroke Centers: Detailed Follow-Up to Brain Attack Coalition Comprehensive Stroke Center Recommendations A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Background— Stroke is a major cause of disability and death. The Brain Attack Coalition has proposed establishment of primary and comprehensive stroke centers to provide appropriate care to stroke patients who require basic and more advanced interventions, respectively. Primary stroke centers have been designated by The Joint Commission since 2003, as well as by various states. The designation of comprehensive stroke centers (CSCs) is now being considered. To assist in this process, we propose a set of metrics and related data that CSCs should track to monitor the quality of care that they provide and to facilitate quality improvement. Methods and Results— We analyzed available guideline statements, reviews, and other literature to identify the major features that distinguish CSCs from primary stroke centers, drafted a set of metrics and related data elements to measure the key components of these aspects of stroke care, and then revised these through an iterative process to reach a consensus. We propose a set of metrics and related data elements that cover the major aspects of specialized care for patients with ischemic cerebrovascular disease and nontraumatic subarachnoid and intracerebral hemorrhages at CSCs. Conclusions— The metrics that we propose are intended to provide a framework for standardized data collection at CSCs to facilitate local quality improvement efforts and to allow for analysis of pooled data from different CSCs that may lead to development of national performance standards for CSCs in the future.

Prognostic value and determinants of ultraearly angiographic vasospasm after aneurysmal subarachnoid hemorrhage.

OBJECTIVE A small number of patients with aneurysmal subarachnoid hemorrhage have angiographic evidence of cerebral vasospasm within 48 hours of the onset of hemorrhage. The present study analyzes the prognostic value and determinants of this ultraearly angiographic finding. METHODS We analyzed prospectively collected data from the placebo-treated group in a multicenter clinical trial conducted at 54 neurosurgical centers in North America. The presence and severity of ultraearly angiographic vasospasm (UEAV) was determined by a blinded review of the admission angiograms. Using logistic regression analysis, we identified independent determinants of UEAV from demographic, clinical, laboratory, and neuroimaging characteristics of the patients. The impact of UEAV on the risk of symptomatic vasospasm and 3-month outcome was analyzed after adjusting for potential confounding factors. RESULTS Of 296 patients in the analysis, 37 (13%) had angiographic evidence of vasospasm at admission. An initial Glasgow Coma Scale score of less than 14 (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.1-6.0), and serum sodium greater than 138 mmol/L (OR, 3.4; 95% CI, 1.5-8.3) were associated with UEAV. UEAV was associated with increased risk of symptomatic vasospasm (OR, 2.5; 95% CI, 1.2-5.4) and poor outcome at 3 months (OR, 2.8; 95% CI, 1.2-6.3), after adjusting for other variables. This risk of symptomatic vasospasm was not influenced by early surgery (within 48 h of hemorrhage onset). Poor outcome was more likely to occur in patients with UEAV who did not undergo early surgery (P = 0.03). CONCLUSION Our analysis suggests that patients with angiographic evidence of vasospasm at admission are at high risk for both symptomatic vasospasm and poor outcome. We also found that early surgery did not aggravate this risk.

A review of selective hypothermia in the management of traumatic brain injury.

OBJECT Traumatic brain injury (TBI) remains a significant cause of morbidity and death in the US and worldwide. Resuscitative systemic hypothermia following TBI has been established as an effective neuroprotective treatment in multiple studies in animals and humans, although this intervention carries with it a significant risk profile as well. Selective, or preferential, methods of inducing cerebral hypothermia have taken precedence over the past few years in order to minimize systemic adverse effects. In this report, the authors explore the current methods available for inducing selective cerebral hypothermia following TBI and review the literature regarding the results of animal and human trials in which these methods have been implemented. METHODS A search of the PubMed archive (National Library of Medicine) and the reference lists of all relevant articles was conducted to identify all animal and human studies pertaining to the use of selective brain cooling, selective hypothermia, preferential hypothermia, or regional hypothermia following TBI. RESULTS Multiple methods of inducing selective cerebral hypothermia are currently in the experimental phases, including surface cooling, intranasal selective hypothermia, transarterial or transvenous endovascular cooling, extraluminal vascular cooling, and epidural cerebral cooling. CONCLUSIONS Several methods of conferring preferential neuroprotection via selective hypothermia currently are being tested. Class I prospective clinical trials are required to assess the safety and efficacy of these methods.

The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study Protocol

Background and Purpose— Epidemiological studies of intracerebral hemorrhage (ICH) have consistently demonstrated variation in incidence, location, age at presentation, and outcomes among non-Hispanic white, black, and Hispanic populations. We report here the design and methods for this large, prospective, multi-center case–control study of ICH. Methods— The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study is a multi-center, prospective case–control study of ICH. Cases are identified by hot-pursuit and enrolled using standard phenotype and risk factor information and include neuroimaging and blood sample collection. Controls are centrally identified by random digit dialing to match cases by age (±5 years), race, ethnicity, sex, and metropolitan region. Results— As of March 22, 2013, 1655 cases of ICH had been recruited into the study, which is 101.5% of the target for that date, and 851 controls had been recruited, which is 67.2% of the target for that date (1267 controls) for a total of 2506 subjects, which is 86.5% of the target for that date (2897 subjects). Of the 1655 cases enrolled, 1640 cases had the case interview entered into the database, of which 628 (38%) were non-Hispanic black, 458 (28%) were non-Hispanic white, and 554 (34%) were Hispanic. Of the 1197 cases with imaging submitted, 876 (73.2%) had a 24 hour follow-up CT available. In addition to CT imaging, 607 cases have had MRI evaluation. Conclusions— The ERICH study is a large, case–control study of ICH with particular emphasis on recruitment of minority populations for the identification of genetic and epidemiological risk factors for ICH and outcomes after ICH.