James Grotta

Guidelines for the Management of Spontaneous Intracerebral Hemorrhage A Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Heart Association

Intracerebral hemorrhage (ICH) is more than twice as common as subarachnoid hemorrhage (SAH) and is much more likely to result in death or major disability than cerebral infarction or SAH.1 Although >315 randomized clinical therapeutic trials for acute ischemic stroke and 78 trials for SAH were complete or ongoing (oral communication, Cochrane Collaboration, May 16, 1995) as of 1995, only the results of 4 small randomized surgical trials (353 total patients)2 3 4 5 and 4 small medical trials (513 total patients)6 7 8 9 of ICH had been published. In these small randomized studies, neither surgical nor medical treatment has been shown conclusively to benefit patients with ICH. Advancing age and hypertension are the most important risk factors for ICH.10 11 12 13 14 15 ICH occurs slightly more frequently among men than women and is significantly more common among young and middle-aged blacks than whites of similar ages.10 16 Reported incidence rates of ICH among Asian populations are also higher than those reported for whites in the United States and Europe. Pathophysiological change in small arteries and arterioles due to sustained hypertension is generally regarded as the most important cause of ICH.11 12 14 17 18 Cerebral amyloid angiopathy is increasingly recognized as a cause of lobar ICH in the elderly.19 20 21 22 23 Other causes of ICH include vascular malformations, ruptured aneurysms, coagulation disorders, use of anticoagulants and thrombolytic agents, hemorrhage into a cerebral infarct, bleeding into brain tumors, and drug abuse.10 Of the estimated 37 000 Americans who experienced an ICH in 1997, 35% to 52% were dead at 1 month; half of the deaths occurred within the first 2 days.1 17 24 Only 10% of patients were living independently at 1 month; 20% were independent …

Guidelines for Thrombolytic Therapy for Acute Stroke: A Supplement to the Guidelines for the Management of Patients With Acute Ischemic Stroke A Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Heart Association

In 1994 a panel of the American Heart Association Stroke Council wrote guidelines on the management of patients with acute ischemic stroke.1 The panel predicted that its recommendations would change as the results of ongoing clinical trials became available. At that time the panel recommended that thrombolytic drugs should not be given to persons with acute ischemic stroke outside the clinical trial setting. Since publication of the guidelines, the results of five clinical trials of intravenously administered thrombolytic drugs have been reported.2 3 4 5 6 The use of intra-arterial thrombolytic drugs continues to be reported. In light of these data, the Stroke Council reviewed the status of thrombolytic therapy and prepared this supplement, which includes recommendations for the use of thrombolytic drugs in clinical practice. In preparing this report, panel members used the rules of evidence for treatments used during the writing of the previous report1 7 (Table 1⇓). The target audience for this statement includes neurologists, emergency physicians, primary care physicians, neurosurgeons, and vascular surgeons who care for persons seen within the first few hours after stroke. View this table: Table 1. Levels of Evidence and Grading of Recommendations for Treatment of Patients With Acute Ischemic Stroke* Measures to expedite clot lysis and restore circulation may limit the extent of brain injury and improve outcome after stroke. Unfortunately, intracranial bleeding was frequent among persons enrolled in studies performed in the late 1960s and 1970s, and the therapy was abandoned8 9 10 (Level of Evidence II). More recently, interest in thrombolytic therapy revived because of development of new drugs and their successful use in the care of persons with myocardial ischemia.11 In addition, a meta-analysis combining data from several pilot studies in stroke suggested that thrombolytic therapy might be useful.12 Available thrombolytic drugs are recombinant tissue plasminogen …

Guidelines for the management of patients with acute ischemic stroke. A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association.

In 1991, about 500 000 Americans had a stroke (400 000 had an ischemic stroke) and more than 143 000 died. More than 3 000 000 people in the .Ignited States have survived a stroke. In 1994 the annual economic costs of stroke due to health care expenses and lost productivity are estimated to be nearly

Finding the Most Powerful Measures of the Effectiveness of Tissue Plasminogen Activator in the NINDS tPA Stroke Trial

20 billion. In spite of these human and financial costs, stroke unfortunately has not received a great deal of attention, and its management has been marred by an element of nihilism. Caplan concludes that past failures to establish effective therapies for stroke are due to problems in clinical trial design, lack of interest in care of stroke, and lack of available technologies to evaluate patients. However, with advances in diagnosis and treatment, stroke can now be managed as the life-threatening emergency that it is. In 1993 the American Heart Association included emergent stroke care as part of its special resuscitation situations for basic and advanced life support. This report builds on that statement. The goal of this special report is to provide information about the current management of acute ischemic stroke. It also provides recommendations for initial care (within 24 hours of stroke) based on currently available data from clinical trials. In the future, many therapies for stroke will be linked to very early (within 6 hours) intervention. No recommendations about rehabilitation or chronic medical or surgical measures to prevent recurrent stroke are made. To prepare this report, the members of the Stroke Council used the rules of evidence for specific treatments that have been used by other panels (Table I). These rules give greater credence to the results of well-designed clinical trials than to anecdotal case reports or case series. The current recommendations will eventually be altered

Streamlining of prehospital stroke management: the golden hour.

Background and Purpose We sought to identify the most powerful binary measures of the treatment effect of tissue plasminogen activator (tPA) in the National Institute of Neurological Disorders and Stroke (NINDS) rTPA Stroke Trial. Methods Using the Classification and Regression Tree (CART) algorithm, we evaluated binary cut points and combination of binary cut points with the 4 clinical scales and head CT imaging measures in the NINDS tPA Stroke Trial at 4 times after treatment: 2 hours, 24 hours, 7 to 10 days, and 3 months. The first analysis focused on detecting evidence of “early activity” of tPA with the use of outcome measures derived from the 2-hour and 24-hour clinical and radiographic measures. The second analysis focused on longer-term outcome and “efficacy” and used outcome measures derived from 7- to 10-day and 3-month measures. After identifying the cut points with the ability to classify patients into the tPA and placebo groups using part I data from the trial, we then used data from part II of the trial to validate the results. Results Of the 5 most powerful outcome measures for early activity of tPA, 4 involved the National Institutes of Health Stroke Scale (NIHSS) score at 24 hours or changes in the NIHSS score from baseline to 24 hours. The best overall single outcome measure was an NIHSS score ≤2 at 24 hours, which provided an odds ratio of 5.4 (95% CI, 2.4 to 12.1) and a projected sample size of 58 per treatment group assuming an &agr; of 0.05 (2-sided test) and a power of 80% using part I data. The top 2 and 3 of the top 5 outcome measures for detecting the longer-term efficacy of tPA also involved the NIHSS score. A Rankin score of 0 or 1 at 3 months was the third most powerful outcome measure. Outcome measures identified by CART from part I data were not as sensitive in detecting the effectiveness of tPA when applied to part II data. Conclusions Measures using the NIHSS and a Rankin score ≤1 were the most sensitive discriminators of the effectiveness of tPA in the NINDS tPA Stroke Trial compared with the other clinical and radiological measures. The outcome measures identified in this exploratory analysis (eg, NIHSS score ≤2 at 24 hours) would be best used as an outcome measure in future phase II trials of recanalization begun within the first 3 hours after stroke onset, with inclusion and exclusion criteria similar to those in the NINDS tPA Stroke Trial.

The Current Status of Neuronal Protective Therapy: Why Have All Neuronal Protective Drugs Worked in Animals but None So Far in Stroke Patients?

Thrombolysis with alteplase administered within a narrow therapeutic window provides an effective therapy for acute ischaemic stroke. However, mainly because of prehospital delay, patients often arrive too late for treatment, and no more than 1-8% of patients with stroke obtain this treatment. We recommend that all links in the prehospital stroke rescue chain must be optimised so that in the future more than a small minority of patients can profit from time-sensitive acute stroke therapy. Measures for improvement include continuous public awareness campaigns, education of emergency medical service personnel, the use of standardised, validated scales for recognition of stroke symptoms and for triaging to the appropriate institution, and advance notification to the receiving hospital. In the future, use of telemedicine technologies for interaction between the emergency site and hospital, and the strategy of treatment directly at the emergency site (mobile stroke unit concept), could contribute to more efficient use of resources and reduce the time taken to instigate treatment to within 60 min--the golden hour--of the onset of the symptoms of stroke.

Graded bioassay for demonstration of brain rescue from experimental acute ischemia in rats.

The implication of several recent reviews and the subtitle of this paper is that animal models may not be relevant to human stroke. I will review neuronal protective therapy and how animal models have

Timing of thrombolysis for acute ischemic stroke: "timing is everything" or "everyone is different".

This study explored the correlation between duration of focal ischemia and infarct volume in spontaneously hypertensive rats as a measure of outcome after neuroprotective intervention. Methods We used 2,3,5-riphenyltetrazolium chloride staining to discriminate infarcted tissue and calculate infarct volume 24 hours after temporary tandem common carotid/middle cerebral artery occlusion lasting 5 to 150 minutes. We used a graded bioassay described by logistic function and executed by computer program (ALLFIT) to evaluate changes in infarct volume after increasing durations of ischemia. The method allowed us to calculate the maximal infarct volume (Volmax) and the duration of ischemia before reperfusion producing half-maximal infarct size (T50). Hypothermia and the N-methyl-D-aspartate antagonist CNS-1102 begun after the onset of ischemia were tested for their ability to reduce Volmax and prolong T50 as analyzed by ALLFTT. Results Volmax was 180.6±22.4 mm3 and T50 was 45.9±5.8 minutes in control rats. Hypothermia (30°C) applied during ischemia reduced Volmax by 66 mm3 and extended T50 by 50% (P<.05 for each comparison). CNS-1102, like hypothermia, extended T50 by 44% but did not have an effect on Volmax. Conclusions Analysis of the changes of infarct size after increasing durations of ischemia indicates that although both were protective, the two treatments tested may exhibit different profiles of efficacy. This method of analyzing ischemiainduced damage may be very sensitive for studying the efficacy and possible clinical use of neuronal protective therapies for hyperacute stroke.

Influence of racial differences on outcomes after thrombolytic therapy in acute ischemic stroke

It is indisputable that in the first 2 to 3 hours of an acute ischemic, the best strategy to maximize recovery is robustly time‐based and depends on getting the artery open as soon as possible. The second law of thermodynamics and the underappreciated effect of clot consistency and size must be accounted for in our efforts to minimize time to recanalization within the first 2 to 3 hours. It is also clear that at later time intervals, beyond 4.5 hours, few patients completely recover even with sustained complete recanalization, and that the ability to recover depends more on physiologic tissue issues than on the duration of the occlusion. Clinical factors as well as imaging should be used to select patients who may benefit from delayed attempts at reperfusion.

Early CT changes of ischemia: limitations of what we know

Background The National Institutes of Neurological Disorders and Stroke and the European Co-operative Acute Stroke III trials enrolled a largely Caucasian population, but the results are often extrapolated onto non-Caucasians. A limited number of nonrandomized studies have proposed that non-Caucasian patients show differential response to tissue plasminogen activator. Aims and/or hypothesis We examined if non-Caucasian patients of mixed national origin within the Virtual International Stroke Trials Archives neuroprotection trials responded differently to tissue plasminogen activator compared with Caucasians. Methods We matched patients within each race-subtype for age, baseline National Institutes of Health Stroke Scales, and diabetes status, and excluded outliers. We tested for an interaction of race ethnicity with tissue plasminogen activator on predicting outcomes at α = 0·05. We compared 90-day ordinal outcome (modified Rankin Scale; primary analysis) and dichotomized outcomes (modified Rankin Scale 0–1; modified Rankin Scale 0–2; survival) within individual race ethnicity. Results One thousand nine hundred forty-six thrombolysed patients (125 Blacks, 39 Asians, and 1821 Caucasians) were matched with 1946 non-thrombolysed patients in each race ethnicity group. Postmatching, there were no imbalances in baseline National Institutes of Health Stroke Scales and age between the groups (P > 0·05). The interaction of tissue plasminogen activator with race ethnicity was nonsignificant in ordinal (P = 0·4) and in dichotomized outcome models (P > 0·05). Ordinal odds for improved outcomes were 1·5 for all patients (P < 0·05). Ordinal odds for Caucasians were 1·5 (P < 0·05); for Blacks, 2·1 (P < 0·05); and for Asians, 1·2 (P > 0·05; 1·6 after 1:2 matching with nonthrombolysed, because of small numbers). Dichotomized functional outcomes improved after thrombolysis overall, in Caucasians, in Blacks (modified Rankin Scale 0–2 only), and in Asians (after 1:2 matching; P > 0·05). Odds for survival were consistent across all groups. Conclusions These results do not suggest a differential response to tissue plasminogen activator based on race ethnicity. Among Asians, data were particularly sparse, and results should be interpreted with caution.