the NINDS TPA Stroke Study GroupBackground and Purpose 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

BACKGROUND The IMS III Trial did not demonstrate clinical benefit of the endovascular approach compared to IV rt-PA alone for moderate or severe ischemic strokes (NIHSS≥8) enrolled within three hours of stroke onset. Late reperfusion of tissue that is no longer salvageable may be one explanation, as suggested by prior exploratory studies showing an association between time to reperfusion and good clinical outcome. We sought to validate this relationship in the large-scale IMS III trial, and consider its implications for future endovascular trials. METHODS The analysis consisted of the endovascular cohort with proximal arterial occlusions in the anterior circulation that achieved angiographic reperfusion (TICI 2–3) during the endovascular procedure (within 7 hours from the onset of symptoms). Logistic regression was used to model good clinical outcome (90-day modified Rankin 0–2) as a function of the time to reperfusion, and prespecified variables were considered for adjustment. FINDINGS Among 240 proximal vessel occlusions, angiographic reperfusion (TICI 2–3) was achieved in 182 (76%). Mean time to reperfusion was 325 minutes (range 180–418 minutes). Longer time for reperfusion was associated with a decreased likelihood of good clinical outcome (RR [95% CI] for every 30 minute delay: unadjusted 0·85 [0·77–0·94]; adjusted 0·88 [0·80–0·98]). INTERPRETATION We confirm that delay in time to angiographic reperfusion leads to a decreased likelihood of good clinical outcome. Achieving rapid reperfusion may be critical for the successes of future acute endovascular trials. FUNDING: NIH/NINDS (study sponsor), Genentech Inc. (study drug - intra-arterial t-PA), EKOS Corp. (device), Concentric Inc. (device), Cordis Neurovascular, Inc. (device), and Boehringer Ingelheim (European Investigator Meeting support).

Thrombolytic agents hold theoretical promise as therapy for cerebral infarction. This study was designed to evaluate the safety of tissue plasminogen activator, to accomplish urgent patient treatment, and to estimate potential efficacy of tissue plasminogen activator. Following neurological evaluation and computed tomography of the brain, patients with acute ischemic stroke were evaluated and treated with intravenous tissue plasminogen activator under an open-label, dose-escalation design within 90 minutes from symptom onset. End points examined included symptomatic and asymptomatic intracranial hematoma, systemic hemorrhage, and neurological outcome at 2 hours, 24 hours, and 3 months. Seventy-four patients were treated within 90 minutes of symptom onset over seven dose tiers of tissue plasminogen activator, ranging from 0.35 mg/kg to 1.08 mg/kg. Intracranial hematoma with associated neurological deterioration occurred in three patients and was related to increasing doses of tissue plasminogen activator (p = 0.045). Intracranial hematoma did not occur in any of the 58 patients treated with less than or equal to 0.85 mg/kg. Major neurological improvement occurred in 22 patients (30%) at 2 hours from the initiation of tissue plasminogen activator and in a total of 34 patients (46%) at 24 hours, but major neurological improvement was not related to increasing doses of tissue plasminogen activator or to stroke type. Patients with acute stroke can be evaluated and treated within 90 minutes. Tissue plasminogen activator for acute ischemic infarction is not without risk, but the potential for clinical benefit justifies a randomized clinical trial. To date, differences in hemorrhagic risk or neurological benefit of tissue plasminogen activator for particular ischemic stroke types are not apparent.

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.

The International Cooperative Study on the Timing of Aneurysm Surgery evaluated the results of surgical and medical management in 3521 patients between December, 1980, and July, 1983. At admission, 75% of patients were in good neurological condition and surgery was performed in 83%. At the 6-month evaluation, 26% of the patients had died and 58% exhibited a complete recovery. Vasospasm and rebleeding were the leading causes of morbidity and mortality in addition to the initial bleed. Predictors for mortality included the patient's decreased level of consciousness and increased age, thickness of the subarachnoid hemorrhage clot on computerized tomography, elevated blood pressure, preexisting medical illnesses, and basilar aneurysms. The results presented here document the status of management in the 1980's.