John R. Marler

Improved Reliability of the NIH Stroke Scale Using Video Training

Despite the frequent use of clinical rating scales in multicenter therapeutic stroke trials, no generally acceptable method exists to train and certify investigators to use the instrument consistently. We desired to train investigators to use the National Institutes of Health Stroke Scale in a study of acute stroke therapy so that all examiners rated patients comparably. Methods We devised a two-camera videotape method that optimizes the visual presentation of examination findings. We then measured the effectiveness of the training by asking each investigator to evaluate a set of 11 patients, also on videotape. We tabulated the evaluations, devised a scoring system, and calculated measures of interobserver agreement among the participants in this study. Results We trained and certified 162 investigators. We found moderate to excellent agreement on most Stroke Scale items (unweighted K>0.60). TWO items, facial paresis and ataxia, exhibited poor agreement (unweighted K<0.40) and should be revised in future editions of the scale. Performance improved with video training compared with previous studies. Inclusion of the motor rating of the unaffected limbs in the total score did not affect reliability. Conclusions Video training and certification is a practical and effective method to standardize the use of examination scales. Two cameras must be used during the taping of patients to accurately present the clinical findings. This method is easily adapted to any study in which a large number of investigators will be enrolling patients at multiple clinical centers.

Early stroke treatment associated with better outcome The NINDS rt-PA Stroke Study

Background The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study showed a similar percentage of intracranial hemorrhage and good outcome in patients 3 months after stroke treatment given 0 to 90 minutes and 91 to 180 minutes after stroke onset. At 24 hours after stroke onset more patients treated 0 to 90 compared to 91 to 180 minutes after stroke onset had improved by four or more points on the NIH Stroke Scale (NIHSS). The authors performed further analyses to characterize the relationship of onset-to-treatment time (OTT) to outcome at 3 months, early improvement at 24 hours, and intracranial hemorrhage within 36 hours. Methods Univariate analyses identified potentially confounding variables associated with OTT that could mask an OTT–treatment interaction. Tests for OTT–treatment interactions adjusting for potential masking confounders were performed. An OTT–treatment interaction was considered significant if p ≤ 0.10, implying that treatment effectiveness was related to OTT. Results For 24-hour improvement, there were no masking confounders identified and there was an OTT–treatment interaction (p = 0.08). For 3-month favorable outcome, the NIHSS met criteria for a masking confounder. After adjusting for NIHSS as a covariate, an OTT–treatment interaction was detected (p = 0.09): the adjusted OR (95% CI) for a favorable 3-month outcome associated with recombinant tissue-type plasminogen activator (rt-PA) was 2.11 (1.33 to 3.35) in the 0 to 90 minute stratum and 1.69 (1.09 to 2.62) in the 91 to 180 minute stratum. In the group treated with rt-PA, after adjusting for baseline NIHSS, an effect of OTT on the occurrence of intracranial hemorrhage was not detected. Conclusions If the NINDS rt-PA Stroke Trial treatment protocol is followed, this analysis suggests that patients treated 0 to 90 minutes from stroke onset with rt-PA have an increased odds of improvement at 24 hours and favorable 3-month outcome compared to patients treated later than 90 minutes. No effect of OTT on intracranial hemorrhage was detected within the group treated with rt-PA, possibly due to low power.

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

Measurements of acute cerebral infarction: lesion size by computed tomography.

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

High-dose intravenous naloxone for the treatment of acute ischemic stroke.

As part of a prospective therapy study of 65 patients with acute, nonhemorrhagic, cerebral infarction, computed tomographic scans of the head were obtained at admission, 7-10 days, and 3 months. The scans were analyzed for the presence, site, size, and volume measurement of the infarction. At 7-10 days, the mean infarction volume as measured by computed tomography was 55 cm3 or about 4 x 4 x 3.5 cm (range = 0-507 cm3). At 3 months, the mean infarction volume decreased by 25% to 41 cm3. For the 26 scans showing infarction at the time of admission, the mean lesion volume was 33 cm3 at admission, 51 cm3 at 7-10 days, and 49 cm3 at 3 months. With lesion size at 7-10 days expressed as percentage of total brain volume, the mean infarction size was only 5%. Of the 49 patients with lesions revealed by computed tomography at 7-10 days, 20 had an infarction of 1% or less of total brain volume, while only six had an infarction of 20% or more of total brain volume. The lesion volumes as measured by the 7-10-day computed tomography correlated with the neurologic examination scores on admission (Spearmans rank-order correlation = 0.78) and with the scores at 1 week (Spearmans rank-order correlation = 0.79).

Early treatment for acute ischemic stroke

To evaluate the safety and possible efficacy of high-dose naloxone for the treatment of acute cerebral ischemia, 38 patients received a loading dose of 160 mg/m2 over 15 minutes followed by a 24-hour infusion at the rate of 80 mg/m2/hr. Nausea and/or vomiting were common side effects. Naloxone was discontinued in seven patients (because of hypotension in one, bradycardia and hypotension in two, myoclonus in one, focal seizures in two, and hypertension in one); all seven patients responded to treatment and no permanent sequelae to naloxone were noted. Twelve of the 38 patients showed early neurologic improvement (by completion of the naloxone loading dose). However, there was no correlation between such a loading dose response and clinical outcome at 3 months. Our experience suggests that naloxone is safe at the dose used, but data for efficacy are inconclusive.

Use of high dose naloxone in acute stroke: Possible side-effects

Excerpt Early treatment for ischemic stroke has been a difficult objective to attain and has been stated to be impractical for several reasons. Stroke patients, who usually have no pain and may not...

Intravenous thrombolysis for acute stroke

The effects of high dose naloxone in humans have not been studied extensively. We treated 36 patients who had acute ischemic cerebral infarction with high doses of naloxone to evaluate potential efficacy and toxicity. All patients were treated with a 160-mg/m2 (4-mg/kg) loading dose followed by 80 mg/m2.h (2 mg/kg.h) x 24 h. There were no statistically significant changes in group mean arterial pressure, respiratory rate, or heart rate in response to the loading dose or infusion, although clinically significant changes did occur in four patients. Twenty-three patients had adverse reactions possibly related to naloxone, the most common of which were nausea (n = 20), bradycardia and/or hypotension (n = 3), myoclonus (n = 1), and hypertension (n = 1). Seven patients had naloxone discontinued for possible adverse reactions. All adverse reactions abated with discontinuation of naloxone and/or pharmacologic therapy when indicated. No deaths were attributable to naloxone treatment. High dose naloxone appears to be well tolerated in the majority of elderly patients with acute cerebral infarction.

Comparison of admission serum glucose concentration with neurologic outcome in acute cerebral infarction. A study in patients given naloxone

Until recently there was no specific therapy for stroke, but the recent publication of the National Institute of Neurological Disorders and Stroke(NINDS) t-PA for Acute Stroke Trial presents the first effective, specific therapy for stroke.1 In considering whether to apply thrombolysis to any given patient, the physician must consider the factors unique to each patient and the scientific literature regarding the therapy. We now review the literature that preceded the publication of the NINDS study to put the positive results into perspective. We selected papers for inclusion in our review in two ways. First, we collected the pivotal works known to one or more of the authors. Second, we performed a Medline retrieval for the years 1966 to 1996 using the search terms cerebrovascular disorders and human thrombolytic therapy, excluding references with the terms myocardial infarction or coronary angiography. We also excluded papers not written primarily in English. This search yielded 178 references. We carefully examined the titles and subject words. We eliminated 32 that appeared to be letters or editorials, 46 that appeared to be review articles with no original data, 10 that were case reports of one or a few patients, 23 that addressed the use of intra-arterial thrombolysis, and 53 that were concerned with other uses of thrombolysis such as removing intracerebral hematomas or preventing vasospasm. We retrieved, critically reviewed, and categorized the 14 remaining papers using the criteria listed in table 1. View this table: Table 1 Criteria used for categorizing publications reviewed here Rationale for cerebral artery thrombolysis. It has been assumed from the earliest writings on stroke and confirmed in recent studies employing vascular imaging techniques that most ischemic strokes result from vascular occlusion caused by thrombus.2,3 In a small minority of cases, ischemia may be caused by other mechanisms such as vasospasm. The …