James C. Torner

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 …

Aneurysmal rebleeding: a preliminary report from the Cooperative Aneurysm Study.

It is generally considered that the peak incidence of rebleeding after aneurysmal subarachnoid hemorrhage is at the end of the 1st or the beginning of the 2nd week after the initial rupture. However, in a series of 2265 patients admitted within 3 days of their first subarachnoid hemorrhage, the peak of rebleeding occurred on the same day as the initial hemorrhage and there was no later peak. These data suggest that new management strategies for minimizing rebleeding must be considered for patients admitted soon after aneurysm rupture.

Prognosis of young adults with ischemic stroke. A long-term follow-up study assessing recurrent vascular events and functional outcome in the Iowa Registry of Stroke in Young Adults.

Background and Purpose Information about the long‐term prognosis of young adults with ischemic stroke is limited. Therefore, we performed a follow‐up assessment of 296 patients with ischemic stroke who are enrolled in the Iowa Registry of Stroke in Young Adults. We studied young adults (age, 15 to 45 years) who were referred to a tertiary medical center for management of ischemic stroke between July 1, 1977, and January 1, 1992. Methods Follow‐up assessments were performed by means of questionnaires, examinations, telephone interviews, review of medical records, and reports from personal physicians. Data about risk factors, coincident medical diseases, etiology of stroke, treatment, recurrent stroke, other vascular events, and deaths were collected. Outcomes were rated with the Glasgow Outcome Scale, Barthel Index, National Institutes of Health stroke scale, and the Mini‐Mental State Examination. Quality of life was assessed with the SF‐36 Health Status questionnaire. Results Follow‐up information about the status of 10 patients was limited except that they were alive. Twenty‐one patients (7%) died as the result of their initial stroke, and another 40 patients (14%) died during a mean follow‐up of 6.0 years. None of the patients aged 25 years or younger at the time of stroke died during follow‐up. Mortality was significantly higher among patients who had a stroke secondary to large‐vessel stroke and it was significantly lower in patients with stroke of unknown etiology than in patients with stroke of other causes (relative risk [RR], 1.7; 95% confidence limits [CL], 1.0 to 2.7; and RR, 0.1; CL, 0 to 0.6; respectively). Recurrent strokes occurred in 23 patients (9%) and were fatal in 9. Another 37 patients were treated by a cardiologist during follow‐up; 3 had had a myocardial infarct. Fourteen additional patients needed major vascular surgery. Outcomes with the Glasgow Outcome Scale and Barthel Index were generally favorable. Still, only 49% of patients were still alive, were not disabled, had not suffered from recurrent vascular events, or had not undergone major vascular surgery. Only 42% of survivors had returned to work. A majority of survivors reported emotional, social, or physical residuals that lessened the quality of life. Conclusions The risks of recurrent vascular events in young adults who have had ischemic stroke are considerable. In addition, a majority of survivors will have residual emotional, social, or physical impairments that hamper employment or lower the quality of life. Further research on the quality of life for young adults who survive stroke is needed. (Stroke. 1994;25:1360‐1365.)

Aspirin as a Promising Agent for Decreasing Incidence of Cerebral Aneurysm Rupture

Background and Purpose— Chronic inflammation is postulated as an important phenomenon in intracranial aneurysm wall pathophysiology. This study was conducted to determine if aspirin use impacts the occurrence of intracranial aneurysm rupture. Methods— Subjects enrolled in the International Study of Unruptured Intracranial Aneurysms (ISUIA) were selected from the prospective untreated cohort (n=1691) in a nested case–control study. Cases were subjects who subsequently had a proven aneurysmal subarachnoid hemorrhage during a 5-year follow-up period. Four control subjects were matched to each case by site and size of aneurysm (58 cases, 213 control subjects). Frequency of aspirin use was determined at baseline interview. Aspirin frequency groups were analyzed for risk of aneurysmal hemorrhage. Bivariable and multivariable analyses were performed using conditional logistic regression. Results— A trend of a protective effect for risk of unruptured intracranial aneurysm rupture was observed. Patients who used aspirin 3× weekly to daily had an OR for hemorrhage of 0.40 (95% CI, 0.18–0.87); reference group, no use of aspirin), patients in the “< once a month” group had an OR of 0.80 (95% CI, 0.31–2.05), and patients in the “> once a month to 2×/week” group had an OR of 0.87 (95% CI, 0.27–2.81; P=0.025). In multivariable risk factor analyses, patients who used aspirin 3 times weekly to daily had a significantly lower odds of hemorrhage (adjusted OR, 0.27; 95% CI, 0.11–0.67; P=0.03) compared with those who never take aspirin. Conclusions— Frequent aspirin use may confer a protective effect for risk of intracranial aneurysm rupture. Future investigation in animal models and clinical studies is needed.

Impairment of endothelium-dependent vasodilation induced by acetylcholine and adenosine triphosphate following experimental subarachnoid hemorrhage.

The effect of subarachnoid hemorrhage (SAH) on endothelium-dependent vasodilation of isolated rabbit basilar artery was examined using an isometric tension recording method. Thirty-five rabbits that had 2 successive blood injections were divided into 3 groups: normal animals (control), 4 days, and 3 weeks after the first SAH. Acetylcholine (ACh) (10(-6)-10(-4) M) and adenosine triphosphate (ATP) (10(-6)-10(-4) M) were used to evoke dose-dependent vasodilation of isolated arterial rings previously contracted by 10(-6) M serotonin. In the animals killed 4 days after the first SAH, both ACh- and ATP-induced relaxation were suppressed, and the degree of relaxation of this group was 38 +/- 4.5% (mean +/- SEM) and 22 +/- 3.9% of the initial contractile tone in response to 10(-4) M ACh and 10(-4) M ATP, respectively. Suppression of the relaxation induced by ATP was seen even in the animals killed 3 weeks after the first SAH. Moreover, pretreatment with hemoglobin (10(-6) and 10(-5) M) inhibited endothelium-dependent vasodilation induced by ACh in the arterial rings from the animals killed 4 days after the first SAH. The present experiments suggest that impairment of the endothelium-dependent vasodilation following SAH may be involved in the pathogenesis of cerebral vasospasm.

Preoperative prognostic factors for rebleeding and survival in aneurysm patients receiving antifibrinolytic therapy: report of the Cooperative Aneurysm Study.

Prognostic factors for mortality and recurrent hemorrhage in the preoperative, 2-week period were determined in 1114 patients who participated in the antifibrinolytic therapy investigations of the Cooperative Aneurysm Study between 1970 and 1977. Factors significantly related to mortality were admission neurological status, diastolic blood pressure, interval to treatment, degree of vasospasm, and medical condition. Factors associated with the likelihood of recurrent hemorrhage were interval to treatment, patients sex, and admission neurological status. These factors need to be considered in the analysis of clinical data in the management of ruptured intracranial aneurysms.

Delay in referral of patients with ruptured aneurysms to neurosurgical attention.

Aneurysmal subarachnoid hemorrhage is a neurosurgical emergency. Early medical intervention is axiomatic for minimizing rebleeding and ischemia from vasospasm and achieving optimum results. The purpose of this study was to document the length and causes of the delay in referral which occur in patients following aneurysmal subarachnoid hemorrhage. The case histories of 150 consecutive patients admitted to The University of Iowa with proven ruptured aneurysms were studied. Medical records from The University of Iowa and referring hospitals were reviewed, and patients, families, and referring physicians interviewed. Overall, only 36% were referred within 48 hours of their first clear cut, recognizable sign or symptom of subarachnoid hemorrhage. Median time to referral was 3.6 days. Delay was due to physician diagnostic problems in 37%, delayed referral policy in 23%, unstable patient condition in 7%, failure of patients to recognize severity of illness in 8%, and logistical reasons in 12%. These data suggest that a large proportion of patients have a delay in achieving definitive neurosurgical care following aneurysm rupture, and that for the most part this delay is avoidable. More emphasis must be placed on public health and primary physician education regarding subarachnoid hemorrhage.

Failure of heparin to prevent progression in progressing ischemic infarction.

Anticoagulation with heparin is frequently recommended for patients with progressing ischemic cerebral infarction, yet little data is available detailing the acute results of treatment with this agent. We report the results of continuous intravenous heparin treatment in 36 consecutive patients admitted with progressing ischemic infarction, all of whom had computed tomography scans to exclude the diagnosis of hemorrhage prior to treatment. Overall, 18 of 36 (50%) had continued neurologic worsening despite treatment. The incidence of further worsening was greater in carotid territory infarctions (14 of 19, 74%) than in either vertebrobasilar (2 of 8, 25%) or lacunar (2 of 9, 22%) infarctions (p less than 0.05, Fishers exact test). These observations suggest that additional controlled studies of the efficacy of heparin in progressing ischemic infarction are warranted.

The unruptured intracranial aneurysm treatment score A multidisciplinary consensus

Objective: We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. Methods: An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr*) (vr* = 0 indicating excellent agreement and vr* = 1 indicating poor agreement). Results: The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1–4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1–4.4) for panel members and 4.5 (95% CI 4.3–4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1–4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9–4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019–0.033). Conclusions: This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.

Influence of timing of admission after aneurysmal subarachnoid hemorrhage on overall outcome. Report of the cooperative aneurysm study.

The overall management results after aneurysmal rupture were studied in 158 patients admitted to the hospital on day 0-3 and 175 patients admitted on day 4-7 following subarachnoid hemorrhage. In this series surgery was planned no sooner than 12 days following the ictus. Despite effective medical and surgical therapy overall results were disappointing: 3 months following the initial hemorrhage only 43% of patients in the 0-3 day group and 53% of patients in the 4-7 day group were capable of independent functional living. Patients admitted on days 4-7 also had a lower mortality rate, re-bled less frequently, and had lower postoperative mortality and morbidity than those admitted on days 0-3. For reasons not well defined, time of admission following aneurysmal SAH has an important influence on outcome. Accordingly, in evaluating outcome for patients with ruptured aneurysms treated with different therapeutic modalities, time of admission must be carefully controlled.