Original Article
Thrombolytic Therapy with Streptokinase in Acute Ischemic Stroke
N Engl J Med 1996; 335:145-150July 18, 1996
- Abstract
Background
In patients with acute ischemic stroke, early treatment with thrombolytic agents is thought to permit reperfusion of ischemic neurons and to promote recovery of function. The Multicenter Acute Stroke Trial — Europe (MAST-E) was designed to assess the efficacy and safety of streptokinase in patients with acute ischemic stroke.
Methods
Patients with moderate-to-severe ischemia in the territory of the middle cerebral artery were randomly assigned to receive streptokinase (1.5 million units over a period of one hour) or placebo within six hours after the onset of stroke. The primary efficacy outcome was a binary criterion combining mortality and severe disability at six months, with severe disability defined as a score of 3 or higher on the Rankin scale. The primary safety outcomes were mortality at 10 days and cerebral hemorrhage.
Results
All randomized patients (156 in the streptokinase group and 154 in the placebo group) were evaluated at six months. The incidence of the primary efficacy outcome was similar in the two groups (124 patients in the streptokinase group and 126 in the placebo group died or had a Rankin score >3). However, the mortality rate at 10 days was significantly higher in the streptokinase group than in the placebo group (34.0 percent vs. 18.2 percent, P = 0.002). The higher rate in the streptokinase group was mainly due to the hemorrhagic transformation of ischemic cerebral infarcts. At six months, more deaths had occurred in the streptokinase group than in the placebo group (73 vs. 59, P = 0.06).
Conclusions
In patients with acute ischemic stroke, treatment with streptokinase resulted in an increase in mortality. The routine use of streptokinase cannot be recommended in acute ischemic stroke.
Media in This Article
Figure 1
Probability of Survival over a Period of Six Months among Patients with Acute Ischemic Stroke Assigned to Receive Streptokinase or Placebo.Table 1
Base-Line Characteristics of 310 Patients with Acute Ischemic Stroke Assigned to Receive Streptokinase or Placebo.Article Activity
- Article
Although stroke is a leading cause of death and disability in developed countries, there is no established treatment for acute ischemic stroke. Reperfusion is one possible approach. Interest in reperfusion with thrombolytic agents has been renewed following the success achieved with thrombolysis in patients with acute myocardial infarction.1,2 The rationale for reperfusion with thrombolytic agents is that early treatment aimed at the recovery of ischemic neurons leads to increased survival and reduced disability. However, thrombolytic therapy carries the risks of symptomatic cerebral bleeding and reperfusion-associated injury.
Since the late 1950s, reports involving over 3000 patients with stroke treated with various thrombolytic agents have been published; most have been reports of individual cases or small series. Only a few small, randomized, controlled trials have been reported, and it is not possible, on the basis of the data from these studies, to determine whether thrombolytic therapy is effective and safe in patients with acute ischemic stroke.3,4 The results of larger randomized trials designed to assess the safety and efficacy of thrombolytic therapy in acute ischemic stroke have recently been published.5-8 We have reported the results of the Multicenter Acute Stroke Trial — Europe (MAST-E) with respect to the safety of streptokinase (based on data from 270 patients). The Data Monitoring Committee recommended that recruitment be stopped early because of an increase in mortality due to intracerebral hemorrhage.9 Here we report the final results, including the outcome at six months for all 310 patients enrolled in the trial before recruitment was stopped.
Methods
Study Protocol
The protocol has been described elsewhere.10 Briefly, MAST-E was a multicenter, double-blind, controlled trial with computerized randomization performed by an independent statistics center. All patients who were hospitalized because of the sudden onset of a focal neurologic deficit attributable to ischemia in the territory of the middle cerebral artery and who could be randomly assigned to a treatment group within six hours after the onset of symptoms were eligible for enrollment. The criteria for exclusion were a mild deficit (MAST score, >5511); the resolution of symptoms before randomization; a computed tomographic (CT) scan showing cerebral hemorrhage or a nonvascular disorder; a previous hemorrhagic stroke or a previous stroke with clinical sequelae; recent surgery or trauma; another illness known to compromise the prognosis; or known or suspected pregnancy. Randomization was stratified according to the center and the MAST score (<20, severe deficit, or 20 to 55, moderate deficit). Patients received either 1.5 million units of streptokinase (Kabikinase, Kabi) or an identical-appearing placebo administered by intravenous infusion over a period of one hour.
Streptokinase and placebo were received in batches at the Drug Supply Center, where they were packaged and numbered nonsequentially. The use of concomitant treatments was left to the discretion of the participating investigators, and details of these treatments were noted on the case-report forms. Quality-control measures included on-site visits and cross-checking of case-report forms and medical records.
The trial was conducted in compliance with the Declaration of Helsinki and approved by the Ethics Committee in Lyon, France, and the West Ethics Committee in Glasgow, United Kingdom. Patients or family members gave written informed consent. Before its commencement, the trial was registered in the International Society for Thrombosis and Haemostasis Registry, the Ottawa Stroke Trials Registry, and the Major Ongoing Stroke Trials Registry.12-14
Outcome Measures and Data Collection
The primary efficacy outcome was a binary criterion combining death and severe disability (Rankin score, >3) six months after admission. The Rankin scale is a six-point scale that assesses the degree of handicap.15 The secondary efficacy outcomes were death, recurrent cerebrovascular events, and ischemic events. The Barthel score, on a 20-point scale that assesses the ability to perform 10 activities of daily living, was determined at the six-month visit.16 The safety outcomes were mortality at 10 days, symptomatic intracranial hemorrhages, and clinically silent intracranial hemorrhages assessed by CT on day 5, or earlier in the event of clinical deterioration.
We calculated that 600 patients should be enrolled to detect a decrease of at least 20 percent in the incidence of the primary efficacy outcome in the streptokinase group, with alpha and beta errors of 5 percent in a two-sided comparison, assuming that the incidence of the primary efficacy outcome in the control group would be 70 percent.
Selection data were collected with the use of a telephone computer system before randomization. Base-line and in-hospital data were collected by the participating investigators and sent to the coordinating center. To ensure a blinded evaluation of the primary efficacy outcome, the six-month follow-up data were collected centrally in France by telephone interviews with each patient, a family member, or the patient's general practitioner by a neurologist unaware of the treatment received by the patient.17 In the United Kingdom, follow-up data were collected by home visits or a review of clinic records. These two methods have been shown to be highly correlated in assessing the outcome of stroke.18 Critical events were documented by the investigators and validated by the Critical Events Committee, which was composed of neurologists not involved in the enrollment or follow-up of patients and unaware of the treatment received.
All CT scans were reviewed independently, with the use of a standard questionnaire, by three neurologists who were unaware of the treatment assignments. CT findings considered to be early signs of stroke included loss of the density contrast of the lentiform nucleus19; loss of the density contrast of the insular ribbon20; and hemispheric sulcus effacement, either alone or in association with hyperdensity of the middle cerebral artery.21 Hemorrhagic transformations were classified as either hemorrhagic infarcts or parenchymal hematomas. Hemorrhagic infarcts have heterogeneous areas of blood with indistinct margins and a speckled or mottled appearance or multiple areas of coalescent hemorrhage within large areas of infarcted tissue, situated in the cortical or basal-ganglia gray matter. Parenchymal hematomas have a homogeneous area of circumscribed hyperdensity, usually with a mass effect and sometimes with ventricular extension.22
Statistical Analysis
The statistical analysis was performed at the independent Statistics Center, with the use of an intention-to-treat approach. Data from the two treatment groups were compared with Student's t-test, Wilcoxon's test, the chi-square test, or Fisher's exact test, as appropriate. For the survival analysis, data were censored at the date of the six-month assessment. The distributions of survival times in the two groups were compared with the log-rank test. A Cox proportional-hazards model was used to make adjustments for the effect of potential confounding variables on in-hospital mortality. All reported P values are two-tailed. The Data Monitoring Committee, composed of scientists not involved in the routine running of the trial, reviewed the safety reports each time the 10-day in-hospital assessment had been completed for 50 patients. Two formal interim analyses were planned: the first after the enrollment of 100 patients, and the second after 300 patients had been followed for six months.
Results
From September 17, 1992, to September 26, 1994, 310 patients were enrolled at 48 centers in France and the United Kingdom. The recommendation of the Data Monitoring Committee to stop recruitment has been reported elsewhere.9 We report here the results for the 310 patients already enrolled when recruitment was stopped (156 in the streptokinase group and 154 in the placebo group). There was no significant difference in the base-line characteristics of the two groups, except for the number of patients with diabetes mellitus (P = 0.05) and the frequency of right-sided brain infarction (P = 0.003), which were higher in the streptokinase group (Table 1Table 1
Base-Line Characteristics of 310 Patients with Acute Ischemic Stroke Assigned to Receive Streptokinase or Placebo.). The median delay from the onset of stroke to treatment was 4.58 hours (first and third quartiles, 3.75 and 5.25 hours) in the streptokinase group and 4.50 hours (first and third quartiles, 3.67 and 5.25 hours) in the placebo group. A total of 148 patients in the streptokinase group and 152 in the placebo group received the full dose. Sixty-five percent of the patients in the streptokinase group and 75 percent in the placebo group received concomitant treatment with heparin, and in 31 percent and 12 percent, respectively (P = 0.04), heparin was administered within 12 hours of randomization. Twenty-one patients in each group received aspirin within 48 hours.The safety and efficacy outcomes are shown in Table 2Table 2
Efficacy and Safety Outcomes in the Streptokinase and Placebo Groups.. A similar number of patients in the two groups had died or were severely disabled at six months. No patients were lost to follow-up. In-hospital deaths and symptomatic cerebral hemorrhages occurred more frequently in the streptokinase group; 26 of the symptomatic cerebral hemorrhages in the streptokinase group were fatal, as compared with 2 in the placebo group (P = 0.001). After adjustment of the proportional-hazards model for the MAST score and the side of brain damage, the rate of in-hospital deaths remained significantly higher in the streptokinase group (hazard ratio, 2.18; 95 percent confidence interval, 1.37 to 3.46; P<0.001). At six months, the mortality rate was higher (but not significantly so) in the streptokinase group than in the placebo group, with a relative risk of 1.22 (95 percent confidence interval, 0.94 to 1.58) (Figure 1Figure 1Probability of Survival over a Period of Six Months among Patients with Acute Ischemic Stroke Assigned to Receive Streptokinase or Placebo.). There was a trend toward less severe disability, as indicated by the Rankin score (P = 0.05) and the Barthel score (P = 0.06) among the survivors in the streptokinase group (Table 3Table 3
Disability Ratings at Six Months.). Among these patients, the mean (±SE) length of hospitalization was similar in the two groups (35.9±3.5 days in the streptokinase group and 30.3±3.0 days in the placebo group), but the patients in the streptokinase group had shorter stays in rehabilitation units or nursing homes (43.2±5.6 days vs. 67.4±5.6 days, P = 0.003).The CT findings at base line and subsequently (between day 1 and day 5) are shown in Table 4Table 4
Findings on Initial and Subsequent CT Scans.. All 310 patients had either no abnormalities on the CT scan or signs suggestive of acute cerebral ischemia on the initial scan. As compared with the placebo group, significantly fewer patients in the streptokinase group had only an infarct on the subsequent CT scan (P<0.001) and more had scans showing any hemorrhage (P<0.001), hemorrhagic infarction (P = 0.03), or parenchymal hematoma (P<0.001).Discussion
The results of this study do not demonstrate that streptokinase is beneficial in the treatment of acute ischemic stroke, since the incidence of the primary efficacy outcome (death or severe disability at six months) was similar in the two groups. In addition, the mortality rate was higher in the streptokinase group, mainly because of hemorrhagic transformation of cerebral infarcts. Imbalances in important prognostic factors at base line are not likely to have influenced the results, since they remained unchanged after adjustment for these factors. In another clinical trial involving patients with acute stroke, hypotension was thought to be the cause of the high mortality rate, because of the loss of autoregulation of cerebral blood flow.23 This is an unlikely explanation of our results, since only 0.6 percent of the patients in our study had hypotensive reactions.
The majority of the patients in both groups received concomitant heparin, although fewer patients in the streptokinase group received this agent, possibly because the early occurrence of hemorrhagic transformation dissuaded the investigators from using heparin. However, concomitant treatment with heparin may partly explain the higher rate of hemorrhagic transformations in the streptokinase group, if it is assumed that heparin potentiates the hemorrhagic effect of streptokinase. The patients enrolled in our trial had a very poor prognosis, with a mortality rate of 38.3 percent and a combined rate of mortality and severe disability of 81.8 percent in the placebo group at six months. It is possible that hemorrhagic transformation induced by thrombolytic therapy occurs more frequently in patients with severe stroke than in those with less severe stroke. To test the hypothesis that there is an interaction between the severity of the stroke and treatment, however, data from less severely affected patients are required.
At the six-month visit, survivors in the streptokinase group, as compared with those in the placebo group, had a greater improvement in function, as judged by their MAST and Barthel scores. Also, fewer patients in the streptokinase group were very severely disabled and more were judged to have normal function on the Rankin scale. One possible explanation for the improved functional status of the survivors in the streptokinase group is that treatment with streptokinase really does improve functioning; another possible explanation is simply that the more severely affected patients died early because of complications of thrombolytic therapy.
In clinical trials involving patients with acute stroke, mortality is obviously not the only relevant measure of efficacy, since stroke is the leading cause of disability in adults.24 Therefore, combining the disability and mortality rates provides a simple indicator of efficacy in the analysis of results.8 However, when the values for the two components of this combined outcome are in opposite directions, as in our trial, the global estimate of the treatment effect is difficult to interpret. One alternative is to integrate death into a categorical scale of disability, with death considered to be the worst state of disability, but this is a questionable assumption.25
Among the five recent trials of thrombolytic therapy in patients with acute stroke, the only trial reporting no increase in mortality at three months was the National Institute of Neurological Disorders and Stroke (NINDS) trial of recombinant tissue plasminogen activator.8 In the Australian Streptokinase (ASK) trial, the preliminary analysis showed a 96.4 percent increase in mortality5; in the European Cooperative Acute Stroke Study (ECASS), there was a 40.9 percent increase6; and in the Multicenter Acute Stroke Trial — Italy (MAST-I), there was a 46.9 percent increase at six months.7
Differences in the designs of the trials may explain the differences in results. The same dose of streptokinase was used in MAST-E, MAST-I, and the ASK trial, whereas tissue plasminogen activator was used in ECASS but at a higher dose than that used in the NINDS trial. In addition, the time from the onset of stroke to treatment was four hours in the ASK trial and six hours in MAST-E, MAST-I, and ECASS, as compared with less than three hours in the NINDS trial. The risk profiles of the study populations also differed among the trials, since the frequency of hemorrhagic transformation in the control group was much lower in the NINDS trial (3.5 percent) than in the other trials (10.9 percent in MAST-I, 36.8 percent in ECASS, and 39.6 percent in MAST-E). The increase in symptomatic intracranial hemorrhage in the treated group, as compared with the placebo group, was similar in all trials. In the NINDS trial, however, this increase did not lead to a higher mortality rate, possibly because of the low risk profile of these patients.
Overall, the results of our trial show an increase in mortality among patients receiving thrombolytic therapy as compared with those receiving placebo, but also provide some evidence that the survivors are less severely disabled. Similar results have been reported in MAST-I7 and ECASS.6 Only the NINDS trial reported less severe disability without an increase in the mortality rate due to intracranial hemorrhages. The possibility cannot be ruled out that the results of the NINDS trial are due to chance; the results of a single trial do not provide sufficient evidence of the efficacy and safety of a drug, especially when similar trials have conflicting results.
Another possible explanation is that the treatment group in the NINDS trial represented a subgroup of responders (i.e., patients more likely to survive and have less severe disability with treatment), but the specific characteristics of such patients have not yet been identified. Until these characteristics are known, the widespread use of thrombolytic therapy in patients with acute stroke cannot be recommended. Since more information must be gleaned from the existing data, the decision has been made to conduct a meta-analysis of the data from the patients in all five trials, in order to identify the subgroup likely to benefit from treatment. This analysis is warranted on both scientific and ethical grounds before an additional, very large trial is undertaken to confirm the results of the NINDS trial.
Supported by grants from the Ministère Français de la Santé and the Structure Régionale d'Evaluation Rhône-Alpes. Kabi provided the streptokinase and placebo but was not involved in conducting the trial or analyzing the data.
We are indebted to Margaret C. Haugh for her editorial assistance.
Source Information
Address reprint requests to Dr. Marc Hommel, Stroke Unit, Clinique Neurologique, Centre Hospitalier Universitaire de Grenoble, B.P. 217, 38043 Grenoble CEDEX 9, France.
The members of the study group are listed in the Appendix. The members of the Writing Committee were M. Hommel, C. Cornu, F. Boutitie, and J.P. Boissel.
Appendix
The following investigators participated in the Multicenter Acute Stroke Trial — Europe: France — Aix en Provence: F. Viallet, D. Bonnefoi-Kyriacou, D. Gayraud, and P. Kiegel; Annecy: J.P. Bissuel, J.B. Driencourt, H. Ruel, L. Guillaume, C. Ruffie, and M. Sirodot; Avignon: P. Valon, L. Michel-Bechet, B. Colin, K. Mourali, and P. Olivier; Belfort: B. Ziegler, M. Feissel, A. Cara, J.P. Faller, and J.B. Braun; Besançon: J.L. Chopard, S. Berges, and E. Berger; Bordeaux: F. Rouanet and J.M. Orgogozo; Boulogne sur Mer: P. Devos, D. Testard, and J. Bultel; Bourges: G. Loubrieu, A. Le Bolloc'h, M. Fallut, B. Bouniol, and E. Pomet; Brest: Y. Mocquard, F. Rouhart, P. Diraison, J.Y. Goas, and F. Zagnoli; Chartres: F. Duriez, B. Rivière, and J.L. Brault; Clermont-Ferrand: R. Colamarino, P. Claveloux, D. Deffond, A. Durieux, and M. Tournilhac; Colmar: E. Baldauf and C. Renglewicz-Destgynder; Dreux: P. Rondepierre, J.M. Brunet, V. Julié-Coaquette, F. Delefosse, H. Voisin, M. Alibert, and S. Naviaux; Dunkerque: J.B. Campagne, R. Messin, E. Bakhache, C. Bouttement, B. Vanrenterghem, C. Masse, N. Lecat, F. Lenfant, F. Souyris, and P. Lambert; Epinal: B. Huttin, D. Gérard, E. Planque, J.L. Alexandre, and B. Gilet; Grenoble: P. Limousin, G. Kok, and J. Lizeretti; Lens: A. Verier and B. Delisse; Lille: D. Caparros-Lefebvre, I. Durieu-Couade, O. Godefroy, P. Goldstein, H. Henon, P. Lestavel, D. Leys, C. Lucas, and F. Mounier-Vehier; Limoges: D. Mathe and S. Clement; Lyon: R. Ducluzeau, S. Meyran, J. Demaziere, B. Coppéré, J. Ninet, M.H. Girard Madoux, C. Gabollet, S. Laplace, O. Matas, B. Turkie, C. Gavaud-Kennoz, H. Lafuma, M. Gallet, M. Lestrevel, J. Granger, G. Rozand, and G. Crettet-Pousset; Macon: J.F. Savet, J. Cavallaro, B. Mangola, and A. Ribier; Maubeuge: T. Rosolacci and V. Neuville; Montbrison: J.P. Chaussinand and J. Chanwar; Mulhouse: S. Courtois; Paris: C. Masson, O. Ille, F. Woimant, P. Amarenco, H. Chabriat, and M.G. Bousser; Poissy: F. Nouailhat, H. Outin, and J. Merrer; Poitiers: J.P. Neau and A.M. Tantot; Reims: J.M. Visy and J. Vaunaize; Rennes: J.F. Pinel and V. De Brughgraeve; Rochefort sur Mer: A. Deydier and M. Hermouet; Roubaix: C. Adnet-Bonte; Rouen: Y. Onnient and E. Guegan-Massardier; Saint-Etienne: B. Tardy, J.C. Bertrand, A. Viallon, P. Lafond, F. Zeni, Y. Page, and I. Cusey; Saint Malo: M. Merienne and S. Legrand; Strasbourg: C. Tranchant and G. Rodier; Thonon: R. Faitg, D. Tavernier, P Piot, T. Gillon, L. Sache, M.H. Schmidt, Y. Zerouali, and P. Feuchère; Toulouse: F. Chollet and B. Guiraud-Chaumeil; Tours: D. Saudeau, H. Devauchelle, and A. Autret; Troyes: R. Decombe, C. Rouques, B. Billaud, and M. Van Rechem; Vannes: P. Kassiotis, B. Legal-Meigne, and F. Brunet-Bourgin. United Kingdom — Glasgow: G.T. McInnes, K.W. Muir, J.L. Reid, and P.F. Semple. Steering Committee — M. Hommel, Grenoble; J.P. Boissel, Lyon; and K.R. Lees, Glasgow. Coordinating and Statistics Center, Lyon — C. Cornu, E. Gauthier, N. Visèle, and F. Boutitie. Coordinating Center, Grenoble — A. Serradj Jaillard, B. Noëlle, S. Perez, and C. Bataille. Data Monitoring Committee — M. Bogaert, Ghent, Belgium; A. Rascol, Toulouse; and K. Überla, Munich, Germany. Neuroradiologic Reviewing Committee — G. Besson, Grenoble; T. Moulin, D. Chavot, T. Crepin-Leblond, and L. Tatu, Besançon; and P. Garnier, Saint-Etienne. Critical Events Reviewing Committee — R. Dumas, Dijon; D. Michel, Saint-Etienne; J. Perret, Grenoble; and L. Rumbach, Besançon. Drug Supply Center — S. Ferry, Lyon. Poison Information Center — J.M. Sappori and J. Descottes, Lyon.
- References
References
1
ISIS-2 (Second International Study of Infarct Survival) Collaborative Group
Web of Science | Medline2
Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto MiocardicoGISSI-2: a factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12 490 patients with acute myocardial infarction. Lancet 1990;336:65-71
Web of Science | Medline3
Wardlaw JM ,Warlow CP . Thrombolysis in acute ischemic stroke: does it work? Stroke 1992;23:1826-1839
CrossRef | Web of Science | Medline4
Hommel M ,Bogousslavsky J . Thrombolytics in acute cerebral ischaemia. Expert Opin Invest Drugs 1994;3:1011-1020
CrossRef5
Donnan GA ,Davis SM ,Chambers BR , et al. Trials of streptokinase in severe acute ischaemic stroke. Lancet 1995;345:578-579
CrossRef | Web of Science | Medline6
Hacke W ,Kaste M ,Fieschi C , et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke: the European Cooperative Acute Stroke Study (ECASS). JAMA 1995;274:1017-1025
CrossRef | Web of Science | Medline7
Multicenter Acute Stroke Trial -- Italy (MAST-I) Group
Web of Science | Medline8
The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group
Full Text | Web of Science | Medline9
Hommel M ,Boissel JP ,Cornu C , et al. Termination of trial of streptokinase in severe acute ischaemic stroke. Lancet 1995;345:57-57
CrossRef | Web of Science | Medline10
The MAST Group
Medline11
Orgogozo JM ,Asplund K ,Boysen G . A unified form for neurological scoring of hemispheric stroke with motor impairment. Stroke 1992;23:1678-1679
CrossRef | Web of Science | Medline12
Boissel JP ,Bossard N . Registry of Multicenter Clinical Trials: twelfth and thirteenth report -- 1990-1991. Thromb Haemost 1992;68:752-778
Web of Science | Medline13
The OSTR Collaborative Group
CrossRef | Medline14
Major ongoing stroke trialsStroke 1994;25:1317-1317
15
van Swieten JC ,Koudstaal PJ ,Visser MC ,Schouten HJ ,van Gijn J . Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1988;19:604-607
CrossRef | Web of Science | Medline16
Mahoney FI ,Barthel DW . Functional evaluation: the Barthel Index. Md State Med J 1965;14:61-65
Medline17
Jaillard-Serradj A . Value of phone interview in stroke outcome assessment. Cerebrovasc Dis 1995;5:269-26918
Candelise L ,Pinardi G ,Aritzu E ,Musicco M . Telephone interview for stroke outcome assessment. Cerebrovasc Dis 1994;4:341-343
CrossRef | Web of Science19
Tomura N ,Uemura K ,Inugami A ,Fujita H ,Higano S ,Shishido F . Early CT finding in cerebral infarction: obscuration of the lentiform nucleus. Radiology 1988;168:463-467
Web of Science | Medline20
Truwit CL ,Barkovich AJ ,Gean-Marton A ,Hibri N ,Norman D . Loss of the insular ribbon: another early CT sign of acute middle cerebral artery infarction. Radiology 1990;176:801-806
Web of Science | Medline21
Tomsick TA ,Brott TG ,Chambers AA , et al. Hyperdense middle cerebral artery sign on CT: efficacy in detecting middle cerebral artery thrombosis. AJNR Am J Neuroradiol 1990;11:473-477
Web of Science | Medline22
Moulin T ,Crepin-Leblond T ,Chopard JL ,Bogousslavsky J . Hemorrhagic infarcts. Eur Neurol 1994;34:64-77
CrossRef | Web of Science | Medline23
Wahlgren NG ,MacMahon DG ,De Keyser J ,Indredavik B ,Ryman T . Intravenous Nimodipine West European Stroke Trial (INVEST) of nimodipine in the treatment of acute ischaemic stroke. Cerebrovasc Dis 1994;4:204-210
CrossRef | Web of Science24
Modan B ,Wagener DK . Some epidemiological aspects of stroke: mortality/morbidity trends, age, sex, race, socioeconomic status. Stroke 1992;23:1230-1236
CrossRef | Web of Science | Medline25
Solomon NA ,Glick HA ,Russo CJ ,Lee J ,Schulman KA . Patient preferences for stroke outcomes. Stroke 1994;25:1721-1725
CrossRef | Web of Science | Medline
- Citing Articles (132)
Citing Articles
1
Paul Acheampong, Gary A Ford. (2012) Pharmacokinetics of alteplase in the treatment of ischaemic stroke. Expert Opinion on Drug Metabolism & Toxicology 8:2, 271-281
CrossRef2
Ryan P. Radecki. (2012) Skepticism about thrombolytics in stroke is not unreasonable. Nature Reviews Neurology
CrossRef3
Philipp Taussky, Rabih G. Tawk, Wilson P. Daugherty, Ricardo A. Hanel. (2011) Medical Therapy for Ischemic Stroke: Review of Intravenous and Intra-Arterial Treatment Options. World Neurosurgery 76:6, S9-S15
CrossRef4
Roger E. Kelley, Sheryl Martin-Schild. (2011) Ischemic Stroke: Emergencies and Management. Neurologic Clinics
CrossRef5
E. Jesus Duffis, Zaid Al-Qudah, Charles J. Prestigiacomo, Chirag Gandhi. (2011) Advanced neuroimaging in acute ischemic stroke: extending the time window for treatment. Neurosurgical FOCUS 30:6, E5
CrossRef6
Harold P. Adams, Patricia H. Davis. 2011. Antithrombotic Therapy for Treatment of Acute Ischemic Stroke. , 971-991.
CrossRef7
Wendy Brown, Lama Al-Khoury, Gilda Tafreshi, Patrick D. Lyden. 2011. Intravenous Thrombolysis. , 945-970.
CrossRef8
J. Mocco, Stanley H. Kim, Bernard R. Bendok, Alan S. Boulos, L. Nelson Hopkins, Elad I. Levy. 2011. Interventional Neuroradiologic Therapy of Atherosclerotic Disease and Vascular Malformations. , 1204-1225.
CrossRef9
Carlos S. Kase, Steven M. Greenberg, J.P. Mohr, Louis R. Caplan. 2011. Intracerebral Hemorrhage. , 531-588.
CrossRef10
P. A. Ringleb, M.-G. Bousser, G. Ford, P. Bath, M. Brainin, V. Caso, Á. Cervera, A.l Chamorro, Charlotte Cordonnier, L. Csiba, A. Davalos, H.-C. Diener, J. Ferro, W. Hacke, M. Hennerici, M. Kaste, P. Langhorne, K. Lees, D. Leys, J. Lodder, H. S. Markus, J.-L. Mas, H. P. Mattle, K. Muir, B. Norrving, V. Obach, S. Paolucci, E. B. Ringelstein, P. D. Schellinger, J. Sivenius, V. Skvortsova, K. Stibrant Sunnerhagen, L. Thomassen, D. Toni, R.r von Kummer, N. Gunnar Wahlgren, M. F. Walker, J. Wardlaw. 2010. Ischaemic Stroke and Transient Ischaemic Attack. , 101-158.
CrossRef11
Edward W. Veillon, James N. Martin. 2010. Pregnancy-Related Stroke. , 235-255.
CrossRef12
Patrik Michel. (2010) Current challenges of stroke treatment. Current Opinion in Neurology 23:1, 29-30
CrossRef13
V. Murray, B. Norrving, P. A. G. Sandercock, A. Terént, J. M. Wardlaw, P. Wester. (2010) The molecular basis of thrombolysis and its clinical application in stroke. Journal of Internal Medicine 267:2, 191-208
CrossRef14
Jaehoon Joung, Dushin Jeong. (2010) The Safety and Efficacy of Recombinant Tissue Plasminogen Activator (r-tPA) in Ischemic Stroke Patients in a Community-based Hospital. Journal of the Korean Geriatrics Society 14:2, 84
CrossRef15
A. Kassner, T.P.L. Roberts, B. Moran, F.L. Silver, D.J. Mikulis. (2009) Recombinant Tissue Plasminogen Activator Increases Blood-Brain Barrier Disruption in Acute Ischemic Stroke: An MR Imaging Permeability Study. American Journal of Neuroradiology 30:10, 1864-1869
CrossRef16
Joanna M Wardlaw, Veronica Murray, Eivind Berge, Gregory J del Zoppo, Joanna M Wardlaw. 2009. Thrombolysis for acute ischaemic stroke. .
CrossRef17
Jonathan Birns, Lalit Kalra. (2009) Thrombolytic therapy for stroke. Therapy 6:5, 733-745
CrossRef18
Gregory J. del Zoppo. 2009. Acute Thrombolysis in Ischemic Cerebrovascular Disease. , 617-650.
CrossRef19
Reza Jahan, Fernando Vinuela. (2009) Treatment of acute ischemic stroke: intravenous and endovascular therapies. Expert Review of Cardiovascular Therapy 7:4, 375-387
CrossRef20
Sung-Il Sohn, A-Hyun Cho. (2009) Thrombolytic Treatment of Acute Stroke. Journal of the Korean Medical Association 52:4, 340
CrossRef21
Aslam M. Khaja. (2008) Acute Ischemic Stroke Management: Administration of Thrombolytics, Neuroprotectants, and General Principles of Medical Management. Neurologic Clinics 26:4, 943-961
CrossRef22
P.D. Schellinger, P. Ringleb, W. Hacke. (2008) Leitlinien zum Management von Patienten mit akutem Hirninfarkt oder TIA der Europäischen Schlaganfallorganisation 2008. Der Nervenarzt 79:10, 1180-1202
CrossRef23
C.A. Cronin, C.J. Weisman, R.H. Llinas. (2008) Stroke Treatment. Annals of the New York Academy of Sciences 1142:1, 159-178
CrossRef24
Anna Finley Caulfield, Christine A.C. Wijman. (2008) Management of Acute Ischemic Stroke. Neurologic Clinics 26:2, 345-371
CrossRef25
Iordanis Gravanis, Stella E Tsirka. (2008) Tissue-type plasminogen activator as a therapeutic target in stroke. Expert Opinion on Therapeutic Targets 12:2, 159-170
CrossRef26
Terence J Quinn, Jesse Dawson, Kennedy R Lees. (2008) Past, present and future of alteplase for acute ischemic stroke. Expert Review of Neurotherapeutics 8:2, 181-192
CrossRef27
(2008) Guidelines for Management of Ischaemic Stroke and Transient Ischaemic Attack 2008. Cerebrovascular Diseases 25:5, 457-507
CrossRef28
P. M. W. Bath, L. J. Gray, N.-G. Wahlgren. (2007) Should data monitoring committees assess efficacy when considering safety in trials in acute stroke?. International Journal of Clinical Practice 61:10, 1749-1755
CrossRef29
Jaishri O. Blakeley, Rafael H. Llinas. (2007) Thrombolytic therapy for acute ischemic stroke. Journal of the Neurological Sciences 261:1-2, 55-62
CrossRef30
Xavier Ustrell-Roig, Joaquín Serena-Leal. (2007) Ictus. Diagnóstico y tratamiento de las enfermedades cerebrovasculares. Revista Española de Cardiología 60:7, 753-769
CrossRef31
Paul Steinbok, Ashutosh Singhal, Ken Poskitt, D. Douglas Cochrane. (2007) EARLY HYPODENSITY ON COMPUTED TOMOGRAPHIC SCAN OF THE BRAIN IN AN ACCIDENTAL PEDIATRIC HEAD INJURY. Neurosurgery 60:4, 689???695
CrossRef32
Sohan Singh Hayreh. (2007) Comment re: multicenter study of the European Assessment Group for Lysis in the Eye (EAGLE) for the treatment of central retinal artery occlusion: design issues and implications. Graefe's Archive for Clinical and Experimental Ophthalmology 245:3, 464-466
CrossRef33
Nicolas Feltgen, Dieter Schmidt, Martin Schumacher. (2007) Response to comment: Multicenter study of the European Assessment Group for Lysis in the Eye (EAGLE-Group) for the treatment of central retinal artery occlusion: design issues and implications. EAGLE study report no. 1. Graefe's Archive for Clinical and Experimental Ophthalmology 245:3, 467-470
CrossRef34
Paul A Lapchak, Dalia M Araujo. (2007) Advances in ischemic stroke treatment: neuroprotective and combination therapies. Expert Opinion on Emerging Drugs 12:1, 97-112
CrossRef35
Fumio Asakura, Hasan Yilmaz, German Abdo, Lucka Sekoranja, Diego Millan, Luca Augsburger, Roman Sztajzel, Daniel A. Ruefenacht, Fabienne Perren, Karl-Olof Lovblad, Katsuya Goto. (2007) Preclinical testing of a new clot-retrieving wire device using polyvinyl alcohol hydrogel vascular models. Neuroradiology 49:3, 243-251
CrossRef36
Xavier Ustrell-Roig, Joaquín Serena-Leal. (2007) Stroke. Diagnosis and Therapeutic Management of Cerebrovascular Disease. Revista Española de Cardiología (English Edition) 60:7, 753-769
CrossRef37
Neal Benowitz. 2006. Medical Complications of Drug Abuse. , 597-694.
CrossRef38
Eric Juttler, Martin Kohrmann, Peter D Schellinger. (2006) Therapy for early reperfusion after stroke. Nature Clinical Practice Cardiovascular Medicine 3:12, 656-663
CrossRef39
Erol Veznedaroglu, Elad I. Levy. (2006) Endovascular Management of Acute Symptomatic Intracranial Arterial Occlusion. Neurosurgery 59:SUPPLEMENT, S3-242-S3-250
CrossRef40
Jerome R Hoffman. (2006) Thrombolysis for stroke: Policy should be based on science, and not on politics, money or fear of malpractice. Emergency Medicine Australasia 18:3, 215-218
CrossRef41
Nicole R Gonzales, James C Grotta. (2006) Alteplase for acute ischemic stroke. Expert Review of Cardiovascular Therapy 4:3, 301-318
CrossRef42
Avi Mazumdar, Colin P Derdeyn. (2006) Fibrinolytic treatment for acute ischaemic stroke. Expert Opinion on Pharmacotherapy 7:3, 287-296
CrossRef43
Paul Bentley, Pankaj Sharma. (2005) Pharmacological treatment of ischemic stroke. Pharmacology & Therapeutics 108:3, 334-352
CrossRef44
Reza Jahan. (2005) Hyperacute Therapy of Ischemic Stroke: Intravenous Thrombolysis. Techniques in Vascular and Interventional Radiology 8:2, 81-86
CrossRef45
Robert Silbergleit, Phillip A. Scott. (2005) Thrombolysis for Acute Stroke: The Incontrovertible, the Controvertible, and the Uncertain. Academic Emergency Medicine 12:4, 348-351
CrossRef46
Jerome R Hoffman, Richelle J Cooper. (2005) Stroke thrombolysis: we need new data, not more reviews. The Lancet Neurology 4:4, 204-205
CrossRef47
James L. Frey. (2005) Recombinant Tissue Plasminogen Activator (rtPA) for Stroke. The Neurologist 11:2, 123-133
CrossRef48
Vasantha Padma, Marc Fisher, Majaz Moonis. (2005) Thrombolytic therapy for acute ischemic stroke: 3 h and beyond. Expert Review of Neurotherapeutics 5:2, 223-233
CrossRef49
William F. Baker. (2005) Thrombolytic Therapy: Current Clinical Practice. Hematology/Oncology Clinics of North America 19:1, 147-181
CrossRef50
Dawn M Bravata. (2005) Intravenous Thrombolysis in Acute Ischaemic Stroke. CNS Drugs 19:4, 295-302
CrossRef51
Richard I Lindley. (2005) Thrombolysis in Acute Ischaemic Stroke. CNS Drugs 19:6, 539-551
CrossRef52
Ken Uchino, Andrei V. Alexandrov, Zsolt Garami, Ashraf El-Mitwalli, Lewis B. Morgenstern, James C. Grotta. (2005) Safety and Feasibility of a Lower Dose Intravenous TPA Therapy for Ischemic Stroke beyond the First Three Hours. Cerebrovascular Diseases 19:4, 260-266
CrossRef53
Kathleen M Burger, Stanley Tuhrim. (2004) Antithrombotic trials in acute ischaemic stroke: a selective review. Expert Opinion on Emerging Drugs 9:2, 303-312
CrossRef54
Jacqueline A Pettersen, Mark E Hudon, Michael D Hill. (2004) Intra-arterial thrombolysis in acute ischemic stroke: a review of pharmacologic approaches. Expert Review of Cardiovascular Therapy 2:2, 285-299
CrossRef55
Peter D Schellinger, Markku Kaste, Werner Hacke. (2004) An update on thrombolytic therapy for acute stroke. Current Opinion in Neurology 17:1, 69-77
CrossRef56
Stephanie L. Mick, Marvin D. Spann, Munjal P. Patel, Robert C. Silich, Norma Bacilious, Lloyd A. Hoffman, Mia Talmor. (2004) Thrombolytic Therapy following Rhytidectomy and Blepharoplasty. Plastic and Reconstructive Surgery 113:2, 19e-24e
CrossRef57
Elad I. Levy, Stanley H. Kim, Bernard R. Bendok, Alan S. Boulos, Andrew R. Xavier, Abutaher M. Yahia, Adnan I. Qureshi, Lee R. Guterman, L. Nelson Hopkins. 2004. Interventional Neuroradiologic Therapy. , 1475-1520.
CrossRef58
Lama Al-Khoury, Patrick D. Lyden. 2004. Intravenous Thrombolysis. , 919-941.
CrossRef59
Wade S. Smith. (2004) Pathophysiology of Focal Cerebral Ischemia: a Therapeutic Perspective. Journal of Vascular and Interventional Radiology 15:1, S3-S12
CrossRef60
J. B. Fiebach, P. D. Schellinger. (2003) Local and Systemic Thrombolysis in Acute Stroke. Imaging Decisions MRI 7:4, 26-30
CrossRef61
Alfredo Quinones-Hinojosa, Mittul Gulati, Vineeta Singh, Michael T. Lawton. (2003) Spontaneous intracerebral hemorrhage due to coagulation disorders. Neurosurgical FOCUS 15:4, 1-17
CrossRef62
Joanna M Wardlaw, Gregory J del Zoppo, Takenori Yamaguchi, Eivind Berge, Joanna M Wardlaw. 2003. Thrombolysis for acute ischaemic stroke. .
CrossRef63
JESSE WEINBERGER, WILLIAM H. FRISHMAN, DAWN TERASHITA. (2003) Drug Therapy of Neurovascular Disease. Cardiology in Review 11:3, 122-146
CrossRef64
William F Baker. (2003) Thrombolytic therapy. Hematology/Oncology Clinics of North America 17:1, 283-311
CrossRef65
Kennedy R Lees, Graeme J Hankey, Werner Hacke. (2003) Design of future acute-stroke treatment trials. The Lancet Neurology 2:1, 54-61
CrossRef66
Paul A Lapchak. (2002) Development of thrombolytic therapy for stroke: a perspective. Expert Opinion on Investigational Drugs 11:11, 1623-1632
CrossRef67
Katayoun Vahedi, Marie-Germaine Bousser. (2002) Thrombolysis in stroke. Current Opinion in Hematology 9:5, 443-447
CrossRef68
Victor J Marder, Daphne Stewart. (2002) Towards safer thrombolytic therapy. Seminars in Hematology 39:3, 206-216
CrossRef69
Kennedy R Lees. (2002) Management of acute stroke. The Lancet Neurology 1:1, 41-50
CrossRef70
Hans-Christian Koennecke. (2002) Systemic thrombolytic therapy of acute ischemic stroke with rtPA. Expert Review of Neurotherapeutics 2:2, 187-201
CrossRef71
Ranko Raicevic, Aco Jovicic, Ljubo Markovic, Dragana Djordjevic, Petar Aleksic, Predrag Peric, Jelena Kostic. (2002) Mjesto i uloga endovaskularnih procedura u terapiji ishemijske bolesti mozga. Vojnosanitetski pregled 59:1, 75-80
CrossRef72
Danilo Toni, Valentina Gallo, Anne Falcou, Corrado Argentino, Cesare Fieschi. (2001) Treatment of Cerebrovascular Diseases: State of the Art and Perspectives. Journal of Cardiovascular Pharmacology 38, S83-S86
CrossRef73
Prem K. Kittusamy, Robert A. Koenigsberg, Daniel J. McCormick. (2001) Abciximab for the treatment of acute distal embolization associated with internal carotid artery angioplasty. Catheterization and Cardiovascular Interventions 54:2, 221-233
CrossRef74
Peter D. Schellinger, Jochen B. Fiebach, Alexander Mohr, Peter A. Ringleb, Olav Jansen, Werner Hacke. (2001) Thrombolytic therapy for ischemic stroke—A review. Part I—Intravenous thrombolysis. Critical Care Medicine 29:9, 1812-1818
CrossRef75
V.J. Marder. (2001) Thrombolytic therapy: 2001. Blood Reviews 15:3, 143-157
CrossRef76
M. Grond. (2001) Clinical Thrombolysis in Stroke. Thrombosis Research 103, S135-S142
CrossRef77
Larry B. Goldstein. (2001) Medical therapy for acute ischemic stroke. Current Atherosclerosis Reports 3:4, 299-306
CrossRef78
K KANDARPA, G BECKER, R FERGUSON, J CONNORSIII, J WOJAK, W LANDOW. (2001) Transcatheter Interventions for the Treatment of Peripheral Atherosclerotic Lesions: Part II. Journal of Vascular and Interventional Radiology 12:7, 807-812
CrossRef79
Imran Barlas, John M. Oropello, Ernest Benjamin. (2001) Neurologic complications in intensive care. Current Opinion in Critical Care 7:2, 68-73
CrossRef80
Diane Schretzman. (2001) Acute ischemic stroke. Dimensions of Critical Care Nursing 20:2, 14-21
CrossRef81
James F. Meschia, Thomas G. Brott. (2001) New insights on thrombolytic treatment of acute ischemic stroke. Current Neurology and Neuroscience Reports 1:1, 19-25
CrossRef82
Rafael Llinas, Louis R. Caplan. (2001) Evidence-based treatment of patients with ischemic cerebrovascular disease. Neurologic Clinics 19:1, 79-105
CrossRef83
R HIGASHIDA, J CONNORSIII. (2001) Should Interventional Radiologists Be Involved In Acute Stroke Intervention?Re: Emergency Interventional Stroke Therapy: A Statement from the American Society of Interventional and Therapeutic Neuroradiology and the Society of Cardiovascular & Interventional Radiology. Journal of Vascular and Interventional Radiology 12:2, 145-146
CrossRef84
Catherine Cornu, Emmanuel Amsallem, Assia Serradj-Jaillard A. (2001) Thrombolytic Therapy for Acute Ischemic Stroke. American Journal of Cardiovascular Drugs 1:4, 281-292
CrossRef85
Louise D McCullough, N.B Beauchamp, Robert Wityk. (2001) Recent Advances in the Diagnosis and Treatment of Stroke. Survey of Ophthalmology 45:4, 317-330
CrossRef86
W. Hacke, M. Kaste, T. Skyhoj Olsen, J.-M. Orgogozo, J. Bogousslavsky. (2000) European Stroke Initiative (EUSI) Recommendations for �Stroke Management�The European Stroke Initiative Writing Committee. European Journal of Neurology 7:6, 607-623
CrossRef87
Annegret Rossler, Jorg Berrouschot, Henryk Barthel, Swen Hesse, Johannes Koster, Dietmar Schneider. (2000) Potential of Rheopheresis for the Treatment of Acute Ischemic Stroke When Initiated Between 6 and 12 Hours. Therapeutic Apheresis and Dialysis 4:5, 358-362
CrossRef88
Wood, Alastair J.J., , Brott, Thomas, Bogousslavsky, Julien, . (2000) Treatment of Acute Ischemic Stroke. New England Journal of Medicine 343:10, 710-722
Full Text89
Sidney A. Cohen, Mohit Trikha, Mary A. Mascelli. (2000) Potential future clinical applications for the GPIIb/IIIa antagonist, abciximab in thrombosis, vascular and oncological indications. Pathology & Oncology Research 6:3, 163-174
CrossRef90
Sohan Singh Hayreh, Jost B Jonas. (2000) Optic disk and retinal nerve fiber layer damage after transient central retinal artery occlusion: an experimental study in rhesus monkeys. American Journal of Ophthalmology 129:6, 786-795
CrossRef91
Robert A. Mericle, Demetrius K. Lopes, Mary Duffy Fronckowiak, Ajay K. Wakhloo, Lee R. Guterman, L. Nelson Hopkins. (2000) A Grading Scale to Predict Outcomes after Intra-arterial Thrombolysis for Stroke Complicated by Contrast Extravasation. Neurosurgery 46:6, 1307-1315
CrossRef92
Bruce A Perler, Kieran Murphy, Yaron Sternbach, Philippe Gailloud, Jay G Shake. (2000) Immediate postoperative thrombolytic therapy: An aggressive strategy for neurologic salvage when cerebral thromboembolism complicates carotid endarterectomy. Journal of Vascular Surgery 31:5, 1033-1037
CrossRef93
James M. Gebel, Joseph P. Broderick. (2000) INTRACEREBRAL HEMORRHAGE. Neurologic Clinics 18:2, 419-438
CrossRef94
Susan L. Hickenbottom, William G. Barsan. (2000) ACUTE ISCHEMIC STROKE THERAPY. Neurologic Clinics 18:2, 379-397
CrossRef95
Sophia Sundararajan, Lewis B. Morgenstern. (2000) Thrombolysis for acute stroke: Is it for everyone?. Current Atherosclerosis Reports 2:2, 97-103
CrossRef96
Harold P. Adams. (2000) Thrombolytics in Acute Ischaemic Stroke. BioDrugs 13:2, 115-126
CrossRef97
Alex Abou-Chebl, Anthony J. Furlan. (2000) Intra-arterial thrombolysis in acute stroke. Current Opinion in Neurology 13:1, 51-55
CrossRef98
Gary M. Nesbitt. (2000) IA Stroke Therapy: The Brain Plumbing How-to Guide. Journal of Vascular and Interventional Radiology 11:2, 340-347
CrossRef99
Keith W. Muir, Margaret Roberts. (2000) Thrombolytic Therapy for Stroke. Drugs & Aging 16:1, 41-54
CrossRef100
Suresh C. Patel, Ashish Mody. (1999) Cerebral hemorrhagic complications of thrombolytic therapy
. Progress in Cardiovascular Diseases 42:3, 217-233
CrossRef101
Sohan Singh Hayreh. (1999) Retinal arterial occlusion with LIF using rTPA11EDITOR’S NOTE:This letter is based on review of the original data provided to Dr. Hayreh, the Discussant for the presentation of the manuscript, “Treatment of Retinal Arterial Occlusion with Local Fibrinolysis Using Recombinant Tissue Plasminogen Activator,” at the 1996 Annual Meeting of the AAO. Some original data were omitted from the published paper (Ophthalmology 1999;106:768–73). The Editor elected to publish Dr. Hayreh’s Discussion as a Letter to the Editor, rather than attached to the paper, in order to permit the authors to respond.. Ophthalmology 106:7, 1236-1238
CrossRef102
Kwiatkowski, Thomas G., Libman, Richard B., Frankel, Michael, Tilley, Barbara C., Morgenstern, Lewis B., Lu, Mei, Broderick, Joseph P., Lewandowski, Christopher A., Marler, John R., Levine, Steven R., Brott, Thomas, . (1999) Effects of Tissue Plasminogen Activator for Acute Ischemic Stroke at One Year. New England Journal of Medicine 340:23, 1781-1787
Full Text103
Sujata Naik-Tolani, John M. Oropello, Ernest Benjamin. (1999) NEUROLOGIC COMPLICATIONS IN THE INTENSIVE CARE UNIT. Clinics in Chest Medicine 20:2, 423-434
CrossRef104
D. Dunbabin. (1999) Reperfusion therapy for stroke. Australian and New Zealand Journal of Medicine 29:3, 462-466
CrossRef105
S. L. Ardern-Holmes, R. Raman, N. E. Anderson, A. J. Charleston, P. Bennett. (1999) Opinion of New Zealand physicians on management of acute ischaemic stroke: results of a national survey. Australian and New Zealand Journal of Medicine 29:3, 324-330
CrossRef106
(1999) Ninth Meeting of the European Neurological Society 5–9 June, 1999, Milan, Italy. Journal of Neurology 246:S1, I1-I185
CrossRef107
Deborah G. Stewart. (1999) 1. Epidemiologic aspects and acute management. Archives of Physical Medicine and Rehabilitation 80:5, S4-S7
CrossRef108
Vigneshwar Kasirajan, Nicholas G Smedira, John Perl, Patrick M McCarthy. (1999) Cerebral embolism associated with left ventricular assist device support and successful therapy with intraarterial urokinase. The Annals of Thoracic Surgery 67:4, 1148-1150
CrossRef109
John J. Halperin. (1999) Neuroborreliosis (nervous system lyme disease). Current Treatment Options in Neurology 1:2, 139-145
CrossRef110
Arthur Pancioli, Rashmi Kothari. (1999) Thrombolytic therapy for acute ischemic stroke. Air Medical Journal 18:2, 56-61
CrossRef111
Bernard P. Chan, Gregory W. Albers. (1999) Acute ischemic stroke. Current Treatment Options in Neurology 1:2, 83-95
CrossRef112
Besson Gérard, Moulin Thierry, Chavot Didier, Tatu Laurent, Garnier Pierre, Crépin-Leblond Thierry. (1998) Intra-observer concordance of the Neuroradiologic Reviewing Committee in CT scan reviewing in MAST-E. Acta Neurologica Scandinavica 98:4, 292-293
CrossRef113
G. L. Lenzi, M. Altieri, G. Bruti, S. Legge, D. Lenzi, I. Pestalozza, D. Tombari, E. Vicenzini, V. Piero. (1998) Pathophysiological approach to stroke therapy. The Italian Journal of Neurological Sciences 19:S1, S4-S7
CrossRef114
Michael D Hill, Vladimir Hachinski. (1998) Stroke treatment: time is brain. The Lancet 352, S10-S14
CrossRef115
Werner Hacke, Markku Kaste, Cesare Fieschi, Rüdiger von Kummer, Antoni Davalos, Dieter Meier, Vincent Larrue, Erich Bluhmki, Stephen Davis, Geoffrey Donnan, Dietmar Schneider, Exuperio Diez-Tejedor, Paul Trouillas. (1998) Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). The Lancet 352:9136, 1245-1251
CrossRef116
Philip Bath. (1998) Alteplase not yet proven for acute ischaemic stroke. The Lancet 352:9136, 1238-1239
CrossRef117
N. Curzen, R. Haque, A. Timmis. (1998) Applications of thrombolytic therapy. Intensive Care Medicine 24:8, 756-768
CrossRef118
Andrew D. Firlik, Howard Yonas, Anthony M. Kaufmann, Lawrence R. Wechsler, Charles A. Jungreis, Melanie B. Fukui, Robert L. Williams. (1998) Relationship between cerebral blood flow and the development of swelling and life-threatening herniation in acute ischemic stroke. Journal of Neurosurgery 89:2, 243-249
CrossRef119
Andrew D. Firlik, Howard Yonas, Anthony M. Kaufmann, Lawrence R. Wechsler, Charles A. Jungreis, Melanie B. Fukui, Robert L. Williams. (1998) Relationship between cerebral blood flow and the development of swelling and life-threatening herniation in acute ischemic stroke. Neurosurgical FOCUS 4:6, E1
CrossRef120
Kennedy R Lees. (1998) Does neuroprotection improve stroke outcome?. The Lancet 351:9114, 1447-1448
CrossRef121
Scott E. Kasner, James C. Grotta. (1998) ISCHEMIC STROKE. Neurologic Clinics 16:2, 355-372
CrossRef122
BASIL E. AKPUNONU, ANAND B. MUTGI, LISA LEE, SADIK KHUDER, DOUGLAS J. FEDERMAN, CAROLINE ROBERTS. (1998) Can a Clinical Score Aid in Early Diagnosis and Treatment of Various Stroke Syndromes?. The American Journal of the Medical Sciences 315:3, 194-198
CrossRef123
Adrian Goldszmidt, Robert J. Wityk. (1998) Recent advances in stroke therapy. Current Opinion in Neurology 11:1, 57-64
CrossRef124
Keith Muir, Kennedy R Lees. (1997) Thrombolytic therapy for acute ischaemic stroke. The Lancet 350:9089, 1476-1477
CrossRef125
(1997) Should Thrombolytic Therapy Be the First-Line Treatment for Acute Ischemic Stroke?. New England Journal of Medicine 337:18, 1309-1313
Full Text126
S. JONAS, A. Q. TRAN, E. EISENBERG, M. AZAM, D. VIERA, S. GRUMET. (1997) Does Effect of a Neuroprotective Agent on Volume of Experimental Animal Cerebral Infarct Predict Effect of the Agent on Clinical Outcome in Human Stroke?. Annals of the New York Academy of Sciences 825:1 Neuroprotecti, 281-287
CrossRef127
Jancie L. Hinkle. (1997) New Developments in Managing Transient Ischemic Attack and Acute Stroke. AACN Clinical Issues: Advanced Practice in Acute and Critical Care 8:2, 205-213
CrossRef128
Alison E. Baird, Andrew Benfield, Gottfried Schlaug, Bettina Siewert, Karl-Olof L
vblad, Robert R. Edelman, Steven Warach. (1997) Enlargement of human cerebral ischemic lesion volumes measured by diffusion-weighted magnetic resonance imaging. Annals of Neurology 41:5, 581-589
CrossRef129
(1997) Thrombolytic Therapy in Acute Ischemic Stroke. New England Journal of Medicine 336:1, 65-67
Full Text130
Clifton W. Callaway. (1997) Improving neurologic outcomes after out-of-hospital cardiac arrest. Prehospital Emergency Care 1:1, 45-57
CrossRef131
Stanley L. Barnwell. (1997) Thrombolytic Therapy for Acute Stroke: Indications, Technique, and Results. Journal of Vascular and Interventional Radiology 8:1, 28-32
CrossRef132
A. G. Dyker, K. R. Lees. (1996) The rationale for new therapies in acute ischaemic stroke. Journal of Clinical Pharmacy and Therapeutics 21:6, 377-391
CrossRef
- Letters
