Combined intravenous and intra-arterial recombinant tissue plasminogen activator in acute ischemic stroke.

BACKGROUND AND PURPOSE: A retrospective analysis was performed on 20 consecutive patients who presented with severe acute ischemic stroke and were evaluated for a combined intravenous (IV) and local intra-arterial (IA) recombinant tissue plasminogen activator (rtPA) thrombolytic approach within 3 hours of onset. METHODS: Twenty consecutive patients with carotid artery distribution strokes were evaluated and treated using a combined IV and IA rtPA approach over a 14-month period (September 1998 to October 1999). rtPA (0.6 mg/kg) was given intravenously (maximum dose 60 mg); 15% of the IV dose was given as bolus, followed by a continuous infusion over 30 minutes. A maximal IA dose, up to 0.3 mg/kg or 24 mg, whichever was less, was given over a maximum of 2 hours. IV treatment was initiated within 3 hours in 19 of 20 patients. All 20 patients underwent angiography, and 16 of 20 patients received local IA rtPA. RESULTS: The median baseline National Institutes of Health Stroke Scale (NIHSS) score for the 20 patients was 21 (range 11 to 31). The median time from stroke onset to IV treatment was 2 hours and 2 minutes, and median time to initiation of IA treatment was 3 hours and 30 minutes. Ten patients (50%) recovered to a modified Rankin Scale (mRS) of 0 or 1; 3 patients (15%), to an mRS of 2; and 5 patients (25%), to an mRS of 4 or 5. One patient (5%) developed a symptomatic intracerebral hemorrhage and eventually died. One other patient (5%) expired because of complications from the stroke. CONCLUSIONS: We believe that the greater-than-expected proportion of favorable outcomes in these patients with severe ischemic stroke reflects the short time to initiation of both IV and IA thrombolysis.

Early carotid endarterectomy for critical carotid artery stenosis after thrombolysis therapy in acute ischemic stroke in the middle cerebral artery.

BACKGROUND AND PURPOSE: Tissue plasminogen activator (tPA) has been shown to be effective for acute ischemic stroke. However, if a high-grade cervical carotid stenosis remains despite tPA therapy, patients are at risk for recurrent stroke. Carotid endarterectomy (CEA) has been shown to be effective in symptomatic patients with high-grade cervical carotid stenosis in reducing the risk of stroke, but it is unknown whether CEA can be performed safely after tPA thrombolysis. We describe our experience with 5 patients who underwent early (<48 hours) CEA for residual high-grade cervical carotid stenosis after thrombolytic therapy for acute ischemic stroke in the middle cerebral artery territory. METHODS: All patients had a critical (>99%) carotid artery stenosis on the symptomatic side after tPA therapy. All patients received intravenous tPA; 3 patients also received intra-aortic tPA. Three patients received intravenous heparin infusion immediately after administration of tPA. All patients showed marked improvement in their National Institutes for Health Stroke Scale scores after treatment with tPA. CEA was then performed within 45 hours (6 hours in 1 patient, 23 hours in 2, 26 hours in 1, and 45 hours in 1). RESULTS: All 5 patients underwent successful CEA. There were no complications related to surgery. At discharge, 2 patients had a normal examination, and the remaining patients had mild deficits. In a long-term follow-up of 5 to 22 months, no patient had a recurrent cerebrovascular event. CONCLUSIONS: Early CEA can be performed safely and successfully in patients after tPA treatment for acute ischemic stroke in appropriately selected patients.

Greater Cincinnati/Northern Kentucky Stroke Study: volume of first-ever ischemic stroke among blacks in a population-based study.

BACKGROUND AND PURPOSE: The volume of ischemic stroke on CT scans has been studied in a standardized fashion in acute stroke therapy trials with median volumes between 10.5 to 55 cm(3). The volume of first-ever ischemic stroke in the population is not known. METHODS: The first phase of the population-based Greater Cincinnati/Northern Kentucky Stroke Study identified all ischemic strokes occurring in blacks in the greater Cincinnati region between January and June of 1993. The patients in this phase of the study who had a first-ever ischemic clinical stroke were identified, and the volume of ischemic stroke was measured. RESULTS: There were 257 verified clinical cases of ischemic stroke, of which 181 had a first-ever ischemic infarct. Imaging was available for 150 of these patients, and 79 had an infarct on the CT or MRI study that was definitely or possibly related to the clinical symptoms. For these patients, volumetric measurements were performed by means of the modified ellipsoid method. The median volume of first-ever ischemic stroke for the 79 patients was 2.5 cm(3) (interquartile range, 0.5 to 8.8 cm(3)). There was a significant relation between location of lesion and infarct size (P<0.001) and between volume and mechanism of stroke (P=0.001). CONCLUSIONS: The volume of first-ever ischemic stroke among blacks in our population-based study is smaller than has been previously reported in acute stroke therapy trials. The large proportion of small, mild strokes in blacks may be an important reason for the low percentage of patients who meet the inclusion criteria for tissue plasminogen activator. Further study is necessary to see if these results are generalizable to a multiracial population.

Thrombolytic therapy for cerebral infarction.

Until recently, no clinically effective therapy for acute ischemic stroke has been available. Recent advances in the use of thrombolytic therapy for ischemic stroke appear promising in clinical care. As the use of thrombolytic therapy in acute stroke progress, emergency physicians (EPs) will become increasingly involved in its implementation. The EP must be cognizant of both prior and ongoing investigations in acute ischemic stroke therapy. To that end, this article reviews research in the field of thrombolytic therapy for acute ischemic stroke.

Teaching basic EMTs endotracheal intubation: can basic EMTs discriminate between endotracheal and esophageal intubation?

HYPOTHESIS: Advanced airway intervention techniques are being considered for use by basic emergency medical technicians (EMTs). It was hypothesized that basic EMTs would be able to discriminate reliably between intratracheal and esophageal endotracheal tube placement in a mannequin model. DESIGN: An airway mannequin with a closed chest cavity was intubated randomly either esophageally or tracheally, and the cuff was inflated. A stethoscope, bag ventilator, and laryngoscope were available next to the mannequin. Placement was assessed by auscultation or direct visualization at the discretion of the EMT. A blinded investigator graded the student. SETTING: A classroom in a large, urban medical center. PARTICIPANTS: Subjects were basic EMTs who volunteered to take part after the conclusion of a six-hour endotracheal intubation training course. RESULTS: Thirty-three subjects were tested. Seventeen of 18 (94%) tracheal intubations and 11 of 15 (73%) esophageal intubations were identified correctly. Only 72% of the students listened to the epigastrium, 81% listened to the lungs, and 85% attempted ventilation. The 10 students who visualized the cords discovered all five esophageal intubations. The 23 students who did not visualize the cords missed four and found six esophageal intubations. CONCLUSION: Basic EMTs had difficulty assessing endotracheal tube placement in a mannequin model. The 27% miss rate for identifying esophageal intubations suggests that basic EMTs will require additional training for safe field use of any airway that requires assessment of tube placement.

Combined IV and intra-arterial thrombolysis for acute ischemic stroke.

Combined IV and intra-arterial (IA) thrombolysis for acute ischemic stroke may offer advantages over either technique alone. Sixty-two nonrandomized patients with NIH Stroke Scale scores of > or =10 who met standard criteria for IV thrombolysis were treated with an IV/IA approach. Three-month modified Rankin Scale scores were 0 to 2 for 50% of patients, mortality was 18%, and symptomatic intracerebral hemorrhage occurred in 8%. IV/IA thrombolysis appeared safe and effective in this group.

Asymmetric angioneurotic edema associated with thrombolysis for acute stroke.

We present a case of acute asymmetric angioneurotic edema associated with the use of recombinant tissue plasminogen activator (rtPA) for acute ischemic stroke. rtPA was administered for an acute ischemic stroke in accordance with the recently reported National Institute of Neurological Disorders and Stroke protocol, after which marked asymmetric angioedema requiring upper-airway control developed. Although atypical and anaphylactoid reactions have been reported with the use of rtPA for acute myocardial infarction, to our knowledge this is the first case report of asymmetric angioedema associated with the use of rtPA for acute ischemic stroke.

Vocal cord dysfunction presenting as acute asthma in a pediatric patient.

We report a pediatric patient with an acute onset of paradoxical vocal cord movement which presented as his first episode of wheezing. History and physical examination suggested the diagnosis of vocal cord dysfunction, which was confirmed by a flexible fiberoptic nasophayrngoscopic examination. This is the first report of paradoxical vocal cord movement being made on initial presentation of wheezing in the emergency department and supports earlier reports that this diagnosis can be made in the pediatric population. The practicing pediatric emergency physician should consider the diagnosis of paradoxical vocal cord dysfunction in the differential diagnosis of wheezing in the pediatric patient, especially if the patient does not have the typical historical and physical findings associated with reactive airway disease.

Pediatric emergency department analgesic practice.

OBJECTIVE: To review recent acute pain management care issues in a pediatric emergency department (ED) in order to identify opportunities for a performance improvement program. DESIGN: Descriptive, retrospective chart review. SETTING: Urban pediatric hospital ED. PARTICIPANTS: Between January 1 and December 31, 1994 consecutive patients identified by ED chart review with the following three acute painful conditions were included; sickle cell vasoocclusive crisis (VOC) not complicated by fever or neurologic symptoms, isolated lower extremity long bone fractures < 12 hours old that did not require a reduction, and second degree burns < 12 hours old. Data collection concluded when between 50 and 55 episodes of each painful condition were identified. MAIN OUTCOME MEASURES: ED analgesic administration, initial analgesic dose, initial time elapsed to analgesic administration, notation of pain relief, and home analgesic instruction. Recommended analgesic starting doses were chosen from the 1992 Agency for Health Care Policy and Research Clinical Practice Guidelines. INTERVENTIONS: None. RESULTS: ED analgesic use for VOC was 100%, for fracture was 31%, and for burn was 26%. A recommended starting analgesic dose was given to 78% with VOC, 69% with fracture, and 79% with burn. Mean time to initial analgesic for VOC was 52 minutes, for fracture was 86 minutes, and for burn was 29 minutes. In those given analgesics, notation of pain relief for fracture was 19% and for burn was 29%, this improved for VOC where it was 88%. Home analgesic instruction for VOC was 100%, for fracture was 74%, and for burn was 27%. CONCLUSION: These data from 1994 document suboptimal analgesic use and home analgesic instruction for children in our ED with burns and fractures. Other opportunities in our ED for acute pain management improvement include optimizing initial analgesic doses, shortening the time elapsed to initial analgesic administration, and documenting the response to pain management.

Cincinnati Prehospital Stroke Scale: reproducibility and validity.

STUDY OBJECTIVE: The Cincinnati Prehospital Stroke Scale (CPSS) is a 3-item scale based on a simplification of the National Institutes of Health (NIH) Stroke Scale. When performed by a physician, it has a high sensitivity and specificity in identifying patients with stroke who are candidates for thrombolysis. The objective of this study was to validate and verify the reproducibility of the CPSS when used by prehospital providers. METHODS: The CPSS was performed and scored by a physician certified in the use of the NIH Stroke Scale (gold standard). Simultaneously, a group of 4 paramedics and EMTs scored the same patient. RESULTS: A total of 860 scales were completed on a convenience sample of 171 patients from the emergency department and neurology inpatient service. Of these patients, 49 had a diagnosis of stroke or transient ischemic attack. High reproducibility was observed among prehospital providers for total score (intraclass correlation coefficient [rI],.89; 95% confidence interval [CI],.87 to.92) and for each scale item: arm weakness, speech, and facial droop (.91,.84, and.75, respectively). There was excellent intraclass correlation between the physician and the prehospital providers for total score (rI,.92; 95% CI,.89 to.93) and for the specific items of the scale (.91,.87, and.78, respectively). Observation by the physician of an abnormality in any 1 of the 3 stroke scale items had a sensitivity of 66% and specificity of 87% in identifying a stroke patient. The sensitivity was 88% for identification of patients with anterior circulation strokes. CONCLUSION: The CPSS has excellent reproducibility among prehospital personnel and physicians. It has good validity in identifying patients with stroke who are candidates for thrombolytic therapy, especially those with anterior circulation stroke.

Safety of air medical transportation after tissue plasminogen activator administration in acute ischemic stroke.

BACKGROUND AND PURPOSE: We sought to determine the safety of air medical transport (AMT) of patients with acute ischemic stroke (AIS) immediately after or during administration of tissue plasminogen activator (tPA). Patients with AIS treated with tPA in nonuniversity hospitals frequently need transfer to tertiary care centers that can provide specialized care. AMT is a widely available mode of transport that is crucial in providing expedient and quality health care to critically ill patients while assuring high level of care during transportation. The safety of AMT of patients with AIS after or during administration of tPA has not been examined. METHODS: We performed retrospective chart review of 24 patients with AIS who were treated with intravenous tPA and transferred by helicopter to the Hospital of the University of Pennsylvania or the University of Cincinnati Hospital. The charts were reviewed for neurological complications, systemic complications, and adherence to the National Institutes of Neurological Disorders and Stroke (NINDS) protocol for AIS management. RESULTS: No major neurological or systemic complications occurred. Four patients had hypertension warranting treatment, 3 patients experienced motion sickness, 1 patient developed a transient confusional state, and 1 patient experienced minor systemic bleeding. Four NINDS protocol violations occurred, all related to blood pressure management. CONCLUSIONS: In this small series, AMT of AIS patients after thrombolysis was not associated with any major neurological or systemic complications. Flight crew education on the NINDS AIS protocol is essential in limiting the number of protocol violations. AMT of patients with AIS provides fast and safe access to tertiary centers that can provide state of the art stroke therapy.

Can emergency department triage nurses predict patients' dispositions?

Early recognition of inpatient bed requirements might be helpful in expediting the admission process through the emergency department (ED). With this in mind, we asked whether ED triage nurses could accurately predict patients' in-hospital dispositions. A prediction was recorded for 521 ED patients, of whom 107 (20.5%) were ultimately admitted to the hospital. Nurses correctly anticipated 66 of 107 hospital admissions (sensitivity = 61.7%, PPV = 61.7%). With respect to predicting specific levels of inpatient care, nurses correctly anticipated 17 of 45 floor admissions (sensitivity = 37.8%, PPV = 34.7%), 14 of 33 step-down/monitored unit admissions (sensitivity = 42.4%, PPV = 48.3%), and 12 of 24 intensive care unit admissions (sensitivity = 50.0%, PPV = 66.7%). Lacking in sensitivity and positive predictive value, particularly with regard to specific levels of inpatient care, triage nurses' predictions may have limited potential to expedite the admission process.

Field trial of endotracheal intubation by basic EMTs.

STUDY OBJECTIVE: The 1994 basic-EMT (EMT-B) curriculum recommended teaching EMT-Bs the skill of endotracheal intubation. In this study we assessed the success and complication rates of endotracheal intubations in the field by EMT-Bs. METHODS: We conducted a prospective clinical trial over a period of 28 months in an urban out-of-hospital EMS system. Four first-responder EMT-B engine companies with paramedic backup received 10 hours; intubation training in three sessions spread over at least 2 weeks. The training module was similar to that of the 1994 EMT-B curriculum and included at least 10 intubations on manikins. The EMTs used manikins with closed chest cavities to learn assessment of endotracheal-tube placement. Patients were eligible for intubation by the EMTs if they were apneic and older than 15 years. We calculated 95% confidence interval (CIs) for intubation success rates. RESULTS: Sixty-six EMT-Bs passed the training examinations and were authorized to perform intubation in the field. Endotracheal intubation was attempted by EMTs in 103 patients; the attempt was successful in 53 (95% CI, 42% to 61%). All patients who were not intubated by EMT-Bs were intubated by paramedics, with the exception of six cases. One attempt at intubation was made in 52 patients, two attempts in 44, and three in 7. Three unrecognized esophageal intubations occurred. CONCLUSION: EMT-Bs trained in a short course successfully intubated about half the patients they encountered in this study. This low intubation success rate calls into question the validity of the endotracheal-intubation training module in the 1994 EMT-B national curriculum.

Public perception of stroke warning signs and knowledge of potential risk factors.

CONTEXT: Decreasing the time from stroke onset to hospital arrival and improving control of stroke risk factors depend on public knowledge of stroke warning signs and risk factors. OBJECTIVE: To assess current public knowledge of stroke warning signs and risk factors. DESIGN: A population-based telephone interview survey using random digit dialing conducted in 1995. SETTING: The Greater Cincinnati, Ohio, metropolitan area, the population of which is similar to that of the United States overall in age, sex, percentage of blacks, and economic status. PARTICIPANTS: Respondents with age, race, and sex that matched the population of patients with acute stroke. MAIN OUTCOME MEASURES: Knowledge of risk factors for stroke and warning signs of stroke as defined by the National Institute of Neurological Disorders and Stroke. RESULTS: Telephone calls were made to 17634 households, which yielded 2642 demographically eligible individuals. Interviews were completed by 1880 respondents (response rate, 71.2%). A total of 1066 respondents (57%) correctly listed at least 1 of the 5 established stroke warning signs, and of all respondents, 1274 (68%) correctly listed at least 1 of the established stroke risk factors. Of the respondents, 469 (57%) of 818 respondents with a history of hypertension listed hypertension, 142 (35%) of 402 respondents who were current smokers listed smoking, and 32 (13%) of 255 respondents with diabetes listed diabetes as a risk factor for stroke. Compared with those younger than 75 years, respondents 75 years or older were less likely to correctly list at least 1 stroke warning sign (60% vs 47%, respectively; P<.001) and were less likely to list at least 1 stroke risk factor (72% vs 56%, respectively; P<.001). CONCLUSION: Considerable education is needed to increase the public's awareness of the warning signs and risk factors for stroke. Respondents with self-reported risk factors for stroke are largely unaware of their increased risk. The population at greatest risk for stroke, the very elderly, are the least knowledgeable about stroke warning signs and risk factors.

The Greater Cincinnati/Northern Kentucky Stroke Study: preliminary first-ever and total incidence rates of stroke among blacks.

BACKGROUND AND PURPOSE: The Greater Cincinnati/Northern Kentucky Stroke Study was designed to be the first large, population-based metropolitan study of temporal trends in stroke incidence rates and outcome within a biracial population. METHODS: We are identifying all hospitalized and autopsied cases of stroke and transient ischemic attack (TIA) among the 1.3 million inhabitants of a five-county region of Greater Cincinnati/Northern Kentucky for the period 7/1/93-6/30/94. We have already prospectively monitored for out-of-hospital stroke and TIAs for this same time period at 128 screening sites, including a random sample of all primary care physicians and nursing homes in the region. We have already identified all hospitalized and autopsied cases of stroke and TIA among blacks for 1/1/93-6/30/93 and report preliminary incidence rates for this 6-month period. RESULTS: The overall incidence rate for all first-ever hospitalized or autopsied stroke (excluding TIAs) among blacks in the Greater Cincinnati region was 288 per 100000 (95% CI, 250 to 325, age- and sex-adjusted to 1990 US population). The overall incidence rate for first-ever and recurrent stroke (excluding TIAs) was 411 per 100000 (95% CI, 366 to 456). By comparison, the overall incidence rate of first-ever stroke among whites in Rochester, Minn, during the period 1985-1989 was 179 per 100000 (95% CI, 164 to 194, age- and-sex adjusted to 1990 US population). The incidence rates among blacks in Greater Cincinnati were substantially greater than the rates among whites in Rochester, Minn, for all age categories except ages 75 and older, for which the rates were similar. CONCLUSIONS: We conservatively estimate that 731100 first-ever or recurrent strokes occurred in the United States during 1996. Studies of first-ever as well as total stroke among biracial and representative populations are critical for understanding temporal trends in the incidence rate and the burden of stroke in the US population.

Incidence rates of first-ever ischemic stroke subtypes among blacks: a population-based study.

BACKGROUND AND PURPOSE: The aim of this study was to determine the incidence rates of ischemic stroke subtypes among blacks. METHODS: Hospitalized and autopsied cases of stroke and transient ischemic attack among the 187 000 blacks in the 5-county region of greater Cincinnati/northern Kentucky From January 1, 1993, through June 30, 1993, were identified. Incidence rates were age- and sex-adjusted to the 1990 US population. Subtype classification was performed after extensive review of all available imaging, laboratory data, clinical information, and past medical history. Case-control comparisons of risk factors were made with age-, race-, and sex-matched control subjects. RESULTS: Annual incidence rates per 100 000 for first-ever ischemic stroke subtypes among blacks were as follows: uncertain cause, 103 (95% confidence interval [CI], 80 to 126); cardioembolic, 56 (95% CI, 40 to 73); small-vessel infarct, 52 (95% CI, 36 to 68); large vessel, 17 (95% CI, 8 to 26); and other causes, 17 (95% CI, 9 to 26). Of the patients diagnosed with an infarct of uncertain cause, 31% underwent echocardiography, 45% underwent carotid ultrasound, and 48% had neither. Compared with age-, race-, and sex- (proportionally) matched control subjects from the greater Cincinnati/northern Kentucky region, the attributable risk of hypertension for all causes of first-ever ischemic stroke is 27% (95% CI, 7 to 43); for diabetes, 21% (95% CI, 11 to 29); and for coronary artery disease, 9% (95% CI, 2 to 16). For small-vessel ischemic stroke, the attributable risk of hypertension is 68% (95% CI, 31 to 85; odds ratio [OR], 5.0), and the attributable risk of diabetes is 30% (95% CI, 10 to 45; OR, 4.4). For cardioembolic stroke, the attributable risk of diabetes is 25% (95% CI, 4 to 41; OR, 3.1). CONCLUSIONS: Stroke of uncertain cause is the most common subtype of ischemic stroke among blacks. Cardioembolic stroke and small-vessel stroke are the most important, identifiable causes of first-ever ischemic stroke among blacks. The incidence rates of cardioembolic and large-vessel stroke are likely underestimated because noninvasive testing of the carotid arteries and echocardiography were not consistently obtained in stroke patients at the 18 regional hospitals. Most small-vessel strokes in blacks can be attributed to hypertension and diabetes.

Decreased perihematomal edema in thrombolysis-related intracerebral hemorrhage compared with spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a highly morbid disease process. Perihematomal edema is reported to contribute to clinical deterioration and death. Recent experimental observations indicate that clotting of the intrahematomal blood is the essential prerequisite for hyperacute perihematomal edema formation rather than blood-brain barrier disruption. METHODS: We compared a series of patients with spontaneous ICH (SICH) to a series of patients with thrombolysis-related ICH (TICH). All patients were imaged within 3 hours of clinical onset. We reviewed relevant neuroimaging features, emphasizing and quantifying perihematomal edema. We then analyzed clinical and radiological differences between the 2 ICH types and determined whether these factors were associated with perihematomal edema. RESULTS: TICHs contained visible perihematomal edema less than half as often as SICHs (31% versus 69%, P<0.001) and had both lower absolute edema volumes (0 cc [25th, 75th percentiles: 0, 6] versus 6 cc [0, 13], P<0.0001) and relative edema volumes (0.16 [0.10, 0.33] versus 0.55 [0.40, 0.83], P<0.0001). Compared with SICHs, TICHs were 3 times larger in volume (median [25th, 75th percentiles] volume 69 cc [30, 106] versus 21 cc [8, 45], P<0.0001), 4 times more frequently lobar in location (62% versus 15%, P<0.001), 80 times more frequently contained blood-fluid level(s) (86% versus 1%, P<0.001), and were more frequently multifocal (22% versus 0%, P<0.001). CONCLUSIONS: The striking qualitative and quantitative lack of perihematomal edema observed in the thrombolysis-related ICHs compared with the SICHs provides the first substantial, although indirect, human evidence that intrahematomal blood clotting is a plausible pathogenetic factor in hyperacute perihematomal edema formation.

Early surgical treatment for supratentorial intracerebral hemorrhage: a randomized feasibility study.

BACKGROUND AND PURPOSE: The safety and the effectiveness of the surgical treatment of spontaneous intracerebral hemorrhage (ICH) remain controversial. To investigate the feasibility of urgent surgical evacuation of ICH, we conducted a small, randomized feasibility study of early surgical treatment versus current nonoperative management in patients with spontaneous supratentorial ICH. METHODS: Patients with spontaneous supratentorial ICH who presented to 1 university and 2 community hospitals were randomized to surgical treatment or best medical treatment. Principal eligibility criteria were ICH volume >10 cm(3) on baseline CT scan with a focal neurological deficit, Glasgow Coma Scale score >4 at the time of enrollment, randomization and therapy within 24 hours of symptom onset, surgery within 3 hours of randomization, and no evidence for ruptured aneurysm or arteriovenous malformation. The primary end point was the 3-month Glasgow Outcome Scale (GOS). A good outcome was defined as a 3-month GOS score >3. RESULTS: Twenty patients were randomized over 24 months, 9 to surgical intervention and 11 to medical treatment. The median time from onset of symptoms to presentation at the treating hospitals was 3 hours and 17 minutes, the time from randomization to surgery was 1 hour and 20 minutes, and the time from onset of symptoms to surgery was 8 hours and 35 minutes. The likelihood of a good outcome (primary outcome measure: GOS score >3) for the surgical treatment group (56%) did not differ significantly from the medical treatment group (36%). There was no significant difference in mortality at 3 months. Analysis of the secondary 3-month outcome measures showed a nonsignificant trend toward a better outcome in the surgical treatment group versus the medical treatment group for the median GOS, Barthel Index, and Rankin Scale and a significant difference in the National Institutes of Health Stroke Scale score (4 versus 14; P=0.04). CONCLUSIONS: Very early surgical treatment for acute ICH is difficult to achieve but feasible at academic medical centers and community hospitals. The trend toward less 3-month morbidity with surgical intervention in patients with spontaneous supratentorial ICH warrants further investigation of very early clot removal in larger randomized clinical trials.

Apolipoprotein E phenotype and the efficacy of intravenous tissue plasminogen activator in acute ischemic stroke.

We used stored plasma samples from 409 patients in the National Institute of Neurological Diseases and Stroke (NINDS) tissue plasminogen activator (t-PA) Stroke Trial to examine the relationship between an apolipoprotein (Apo) E2 or an Apo E4 phenotype and a favorable outcome 3 months after stroke, the risk of intracerebral hemorrhage, and the response to intravenous t-PA therapy. For the 27 patients with an Apo E2 phenotype who were treated with t-PA, the odds ratio (OR) of a favorable outcome at 3 months was 6.4 [95% confidence interval (CI) 2.7-15.3%] compared to the 161 patients without an Apo E2 phenotype who were treated with placebo. The 190 patients treated with t-PA who did not have an Apo E2 phenotype also had a greater, though less pronounced, likelihood of a favorable outcome (OR 2.0, 95% CI 1.2-3.2%) than patients without an Apo E2 phenotype treated with placebo. For the 31 patients with an Apo E2 phenotype treated with placebo, the OR of a favorable 3 month outcome was 0.8 (95% CI 0.4-1.7%) compared to the 161 patients without an Apo E2 phenotype treated with placebo. This interaction between treatment and Apo E2 status persisted after adjustment for baseline variables previously associated with 3 month outcome, for differences in the baseline variables in the two treatment groups and in the Apo E2-positive and -negative groups, and for a previously reported time-to-treatment x treatment interaction (p = 0.03). Apo E4 phenotype, present in 111 (27%) of the 409 patients, was not related to a favorable 3 month outcome, response to t-PA, 3 month mortality, or risk of intracerebral hemorrhage. We conclude that the efficacy of intravenous t-PA in patients with acute ischemic stroke may be enhanced in patients who have an Apo E2 phenotype, whereas the Apo E2 phenotype alone is not associated with a detectable benefit on stroke outcome at 3 months in patients not given t-PA. In contrast to prior studies of head injury and stroke, we could not detect a relationship between Apo E4 phenotype and clinical outcome.