Administration Of Tissue-type Plasminogen Activator Research Articles

A Study of Factors Affecting Functional Outcomes in Patients With Successful Recanalization by Mechanical Thrombectomy.

Reperfusion therapy is typically performed in cases with acute cerebral infarction. Mechanical thrombectomy (MT) achieves superior recanalization and favorable outcomes. However, some patients have poor functional prognosis despite successful recanalization. We investigated factors affecting functional prognosis after MT with good reperfusion. Among the 205 consecutive cases with ischemic stroke treated with MT at our center from January 1, 2019 to March 31, 2021, 168 with successful recanalization were included. Factors affecting early neurological improvement (ENI) and modified Rankin Scale (mRS) scores were reviewed retrospectively. There were 93 (55%) cases with ENI and 75 (45%) without ENI. The times from onset to recombinant tissue-type plasminogen activator administration and recanalization in ENI cases were shorter than those in non-ENI cases. However, non-ENI cases had significantly higher Fazekas grades for white matter lesions. In multivariate analysis, the Fazekas grade was related to ENI (odds ratio [OR]=0.572, 95% confidence interval [CI]=0.345-0.948). The mRS score at discharge was 0-2 in 64 cases (good outcome) and 3-6 in 104 cases (poor outcome). Patients with a poor outcome had a significantly higher age, National Institutes of Health Stroke Scale (NIHSS) score, and Fazekas grade. Multivariate analysis revealed that the NIHSS score (OR=1.073, 95% CI=1.020-1.129) and Fazekas grade (OR=2.162, 95% CI=1.458-3.205) at hospitalization affected the mRS score at discharge. There is a correlation of greater severity of white matter lesions with poorer ENI and clinical outcomes at discharge post-MT.

Buffer Coefficient as a Predictor of the Prognosis of Massive Cerebral Infarction

To evaluate the prognostic value of the buffer coefficient, calculated as the ratio of the buffer volume (volume of intracranial cerebrospinal fluid) at the peak of brain edema to the baseline brain volume, and some other parameters in patients with massive cerebral infarction (MCI). The cohort comprised 161 patients with MCI who were divided into good and poor prognosis groups according to modified Rankin Scale score at 90 days after onset. Differences in clinical and imaging parameters between these groups were analyzed by univariate analysis, and multifactorial binary logistic regression analysis was used to further identify influencing factors that were significantly different. Receiver operating characteristic curve was used to evaluate the diagnostic performance between the buffer volume and the buffer coefficient. The findings showed that a history of atrial fibrillation, intravenous tissue-type plasminogen activator administration, successful reperfusion, successful craniectomy, low-density lesion volume, brain volume, buffer volume, and buffer coefficient were significantly different between the poor and good prognosis groups (P < 0.05 for all comparisons). Multifactorial binary logistic regression analyses revealed that patients who had large low-density lesion volume and patients who had not achieved successful reperfusion or received intravenous tissue-type plasminogen activator were likely to have a poor prognosis (P < 0.05). The buffer coefficient was identified as an independent predictive factor for MCI (P < 0.001). The area under the receiver operating characteristic curve for the buffer coefficient was 0.862. When the cutoff value was 9.3%, sensitivity of predicting poor prognosis of patients with MCI was 94.7%. The buffer coefficient has potential benefits as a prognostic indicator for MCI that can be used to detect even subtle changes in brain edema.

The Feasibility of Mechanical Thrombectomy on Single-Plane Angiosuite: An In-Depth Analysis of Procedure Time

Introduction: Mechanical thrombectomy (MT) is usually performed on biplane (BP) angiosuites. When the BP angiosuite is not available, the single-plane (SP) angiosuite may be a substitute. However, the feasibility of MT performed on the SP angiosuite is yet to be elucidated. Therefore, we investigated the alternative effect of the SP angiosuite on the detailed division of procedure time, recanalization rate, and outcome in patients with anterior circulation infarction. Methods: The subjects included 80 consecutive patients with anterior circulation infarction who underwent MT at our hospital between May 2015 and December 2020. Demographics and characteristics of the BP and SP groups were assessed and compared. The time from puncture to guiding catheter placement (P-G), time from guiding catheter placement to recanalization (G-R), and time from puncture to recanalization (P-R) were also extracted. A good outcome was defined as a modified Rankin scale score ≤2 at 3 months. Results: Of the 80 patients, 67 and 13 were treated with BP and SP angiosuites, respectively. There were no differences in age, sex, complications, Alberta Stroke Program Early CT Score, National Institutes of Health Stroke Scale score at onset, occlusion site, rate of recombinant tissue-type plasminogen activator administration, stroke subtype, recanalization rate, and complications between the 2 groups. The rate of a good outcome was not different between the 2 groups. P-G was significantly longer in the SP group than in the BP group, whereas there was no significant difference in G-R and P-R between the 2 groups (P-G: BP 29.9 ± 21.8 vs. SP 48.5 ± 43.6 min, p = 0.04). Conclusion: MT performed on the SP angiosuite tended to prolong the time for guiding catheter placement. However, there was no difference in the overall procedure time, recanalization rate, or outcome between BP and SP angiosuites. Therefore, if the BP angiosuite is not available, the use of the SP angiosuite should be encouraged.

Diabetes Mellitus/Poststroke Hyperglycemia: a Detrimental Factor for tPA Thrombolytic Stroke Therapy.

Intravenous administration of tissue-type plasminogen activator (IV tPA) therapy has long been considered a mainstay in ischemic stroke management. However, patients respond to IV tPA therapy unequally with some subsets of patients having worsened outcomes after treatment. In particular, diabetes mellitus (DM) is recognized as a clinically important vascular comorbidity that leads to lower recanalization rates and increased risks of hemorrhagic transformation (HT). In this short-review, we summarize the recent advances in understanding of the underlying mechanisms involved in post-IV tPA worsening of outcome in diabetic stroke. Potential pathologic factors that are related to the suboptimal tPA recanalization in diabetic stroke include higher plasma plasminogen activator inhibitor (PAI)-1 level, diabetic atherogenic vascular damage, glycation of the tPA receptor annexin A2, and alterations in fibrin clot density. While factors contributing to the exacerbation of HT in diabetic stroke include hyperglycemia, vascular oxidative stress, and inflammation, tPA neurovascular toxicity and imbalance in extracellular proteolysis are discussed. Besides, impaired collaterals in DM also compromise the efficacy of IV tPA therapy. Additionally, several tPA combination approaches developed from experimental studies that may help to optimize IV tPA therapy are also briefly summarized. In summary, more research efforts are needed to improve the safety and efficacy of IV tPA therapy in ischemic stroke patients with DM/poststroke hyperglycemia.

Evaluation of the Accuracy Equivalence of Head CT Interpretations in Acute Stroke Patients Using a Smartphone, a Laptop, or a Medical Workstation

PurposeTo evaluate and compare the clinical performance of observers interpreting head CT images from patients with symptoms of acute stroke with a medical workstation or a smartphone or laptop reading system. Materials and methodsOur institutional review board approved this retrospective study and waived the requirement for informed consent. We employed a factorial design including 2,256 interpretations (188 patients × 4 neuroradiologists × 3 reading systems). Accuracy equivalence tests, at a threshold of 5% and 10%, were performed for the following variables: detection of imaging contraindications for intravenous recombinant tissue-type plasminogen activator administration (eg, hemorrhagic lesions), ischemic lesions, hyperdense arteries, and acute ischemic lesions. For each clinical variable, the sensitivity, specificity, and receiver operating characteristic (ROC) curves were evaluated. ResultsFor each variable, the shapes of the ROC curves were very similar for all of the reading systems, indicating similar observer performance with different specificities and sensitivities. For all the clinical variables, the areas under the ROC curves were equivalent for all of the reading systems at a 10% threshold and were equivalent at a 5% threshold for hemorrhagic lesions, hyperdense middle cerebral artery, and acute ischemic lesion in the middle cerebral artery territory. There was no more than 30 seconds of difference between the reading time of the mobile devices compared with that for the medical workstation. ConclusionThe results of this pilot study showed equivalent diagnostic accuracy when using smartphone and laptops compared with medical monitors to interpret head CT images of patients with symptoms of acute stroke.

Benchmarking Telestroke Proficiency: Page-to-Needle Time Among Neurovascular Fellows and Attendings.

Formal telestroke training for neurovascular fellows (NVFs) is necessary because of growing use of telestroke technologies in the management of acute ischemic stroke; yet, educational approaches and training benchmarks are not formalized. Time between telestroke consultant page and tissue-type plasminogen activator administration (page-to-needle time, PTNT) can provide an objective measure of proficiency. We compared PTNT between NVFs and neurovascular attendings (NVAs) and evaluated changes in PTNT with experience. We identified suspected acute ischemic stroke patients in our telestroke registry from July 2013 to December 2015 who received tissue-type plasminogen activator. Using multivariable quantile regression, we estimated the difference and 95% confidence interval in median PTNT between NVFs and NVAs. We also report the coefficient of change in PTNT over increasing number of telestroke consults. NVFs evaluated 53.7% of 618 tissue-type plasminogen activator cases over telestroke. NVAs had significantly shorter PTNT compared with NVFs, with a difference in median PTNT of -9 minutes (95% confidence interval, -12.3 to -5.7). This difference persisted when adjusted for relative tissue-type plasminogen activator contraindications. For each additional telestroke consult, PTNT decreased by 0.07 minutes for NVFs or NVAs (P=0.02 and <0.01, respectively). PTNT improves by ≈1 minute for every 14 consults for both NVFs and NVAs. Our findings support the importance of integrating telestroke training into supervised neurovascular fellowships to increase proficiency prior to independent practice and suggest that PTNT can be a benchmark for tracking proficiency.

Efficacy of Alteplase in a Mouse Model of Acute Ischemic Stroke: A Retrospective Pooled Analysis.

The debate over the fact that experimental drugs proposed for the treatment of stroke fail in the translation to the clinical situation has attracted considerable attention in the literature. In this context, we present a retrospective pooled analysis of a large data set from preclinical studies, to examine the effects of early versus late administration of intravenous recombinant tissue-type plasminogen activator. We collected data from 26 individual studies from 9 international centers (13 researchers; 716 animals) that compared recombinant tissue-type plasminogen activator with controls, in a unique mouse model of thromboembolic stroke induced by an in situ injection of thrombin into the middle cerebral artery. Studies were classified into early (<3 hours) versus late (≥3 hours) drug administration. Final infarct volumes, assessed by histology or magnetic resonance imaging, were compared in each study, and the absolute differences were pooled in a random-effect meta-analysis. The influence of time of administration was tested. When compared with saline controls, early recombinant tissue-type plasminogen activator administration was associated with a significant benefit (absolute difference, -6.63 mm(3); 95% confidence interval, -9.08 to -4.17; I(2)=76%), whereas late recombinant tissue-type plasminogen activator treatment showed a deleterious effect (+5.06 mm(3); 95% confidence interval, +2.78 to +7.34; I(2)=42%; Pint<0.00001). Results remained unchanged after subgroup analyses. Our results provide the basis needed for the design of future preclinical studies on recanalization therapies using this model of thromboembolic stroke in mice. The power analysis reveals that a multicenter trial would require 123 animals per group instead of 40 for a single-center trial.

Is the Susceptibility Vessel Sign on 3-Tesla Magnetic Resonance T2*-Weighted Imaging a Useful Tool to Predict Recanalization in Intravenous Tissue Plasminogen Activator?

The aim of this study was to investigate the independent factors associated with the absence of recanalization approximately 24h after intravenous administration of tissue-type plasminogen activator (IV TPA). The previous studies have been conducted using 1.5-Tesla (T) magnetic resonance imaging (MRI). We studied whether the characteristics of 3-T MRI findings were useful to predict outcome and recanalization after IV tPA. Patients with internal carotid artery (ICA) or middle cerebral artery (MCA) (horizontal portion, M1; Sylvian portion, M2) occlusion and treated by IV tPA were enrolled. We studied whether the presence of susceptibility vessel sign (SVS) at M1 and low clot burden score on T2*-weighted imaging (T2*-CBS) on 3-T MRI were associated with the absence of recanalization. A total of 49 patients were enrolled (27 men; mean age, 73.9 years). MR angiography obtained approximately 24h after IV tPA revealed recanalization in 21 (42.9 %) patients. Independent factors associated with the absence of recanalization included ICA or proximal M1 occlusion (odds ratio, 69.6; 95 % confidence interval, 5.05-958.8, p = 0.002). In this study, an independent factor associated with the absence of recanalization may be proximal occlusion of the cerebral arteries rather than SVS in the MCA or low T2*-CBS on 3-T MRI.

Chronic kidney disease and bleeding complications after intravenous thrombolytic therapy for acute ischemic stroke.

The safety of intravenous thrombolysis in ischemic stroke (IS) patients with chronic kidney disease (CKD) is uncertain. We assessed whether CKD is associated with bleeding complications after intravenous tissue-type plasminogen activator administration to patients with IS. Data were analyzed from 44 410 patients with IS treated with intravenous tissue-type plasminogen activator in the Get With The Guidelines-Stroke Program. Glomerular filtration rate based on admission serum creatinine was categorized as dichotomous (presence of CKD as <60) or as distinct categories: normal (≥90), mild (≥60-<90), moderate (≥30-< 60), severe (≥15-<30), and kidney failure (<15 or dialysis). Primary outcomes evaluated were symptomatic intracranial hemorrhage and serious systemic hemorrhage; secondary outcomes were in-hospital mortality, independent functional status. There were 15 191 of 44 410 (34%) intravenous tissue-type plasminogen activator-treated IS patients with CKD. Presence of CKD (versus no CKD) was not associated with risk-adjusted symptomatic intracranial hemorrhage (adjusted odds ratio, 1.0; 95% confidence interval: 0.91-1.10) or serious systemic hemorrhage (adjusted odds ratio, 0.97; 95% confidence interval: 0.80-1.18) and did not significantly vary by kidney dysfunction stage for either of these primary end points in multivariable analyses. Compared with patients with normal kidney function, those with CKD were more likely to die in the hospital (adjusted odds ratio, 1.22; 95% confidence interval: 1.14-1.32) and have an unfavorable discharge functional status (adjusted odds ratio, 1.13; 95% CI: 1.07-1.19). Presence of CKD among patients with IS treated with intravenous tissue-type plasminogen activator is associated with higher unadjusted odds of symptomatic intracranial hemorrhage or serious systemic hemorrhage, but this is explained by non-CKD related factors.

Strategies Used by Hospitals to Improve Speed of Tissue-Type Plasminogen Activator Treatment in Acute Ischemic Stroke

The benefits of intravenous tissue-type plasminogen activator in acute ischemic stroke are time dependent, and several strategies have been reported to be associated with more rapid door-to-needle (DTN) times. However, the extent to which hospitals are using these strategies and their association with DTN times have not been well studied. We surveyed 304 Get With The Guidelines-Stroke hospitals joining Stroke regarding their baseline use of strategies to reduce DTN times in the January 2008 to December 2009 time frame before the initiation of Stroke and determined the association between hospital strategies and DTN times. Among 5460 patients receiving tissue-type plasminogen activator within 3 hours of symptom onset in surveyed hospitals, the median DTN time was 72 minutes (interquartile range, 55-94). Reported use of the different strategies varied considerably. Of 11 hospital strategies analyzed individually by multivariable analysis, 3 strategies were independently associated with shorter DTN times. These included rapid triage/stroke team notification (209/304 [69%] hospitals, 8.1-minute reduction in DTN time), single-call activation system (190/304 [63%] hospitals, 4.3 minutes), and tissue-type plasminogen activator stored in the emergency department (189/304 [62%] hospitals, 3.5 minutes). When analyzed incrementally, hospitals that used a greater number of strategies had shorter DTN times with 1.3 minutes (adjusted mean difference) saved for each strategy implemented (14 minutes if all strategies were used). Although the majority of participating hospitals reported using some strategy to reduce delays in tissue-type plasminogen activator administration for acute ischemic stroke, the strategies applied vary considerably and those most strongly associated with shorter DTN times were applied relatively less frequently.

IL1B and VWF Variants Are Associated With Fibrinolytic Early Recanalization in Patients With Ischemic Stroke

There is a great interindividual variability among patients with acute ischemic stroke regarding the response to intravenous tissue-type plasminogen activator treatment. The aim of this study was to identify genetic variants associated with recanalization, and thus treatment efficacy, after tissue-type plasminogen activator administration. A total of 140 single nucleotide polymorphisms from 97 candidate genes were successfully genotyped by SNPlex in 2 cohorts, accounting for 497 prospectively recruited tissue-type plasminogen activator-treated patients, of whom 33% recanalized during tissue-type plasminogen activator infusion. Functional studies were then performed, including assessment of interleukin 1B mRNA levels and von Willebrand factor, FIII, FVII, FVIII, and FX protein activity. After replication, the following single nucleotide polymorphisms were associated with early recanalization: rs1143627 in IL1B gene (CC: 53.1% of recanalization, A-carriers: 32.7%; P=0.022; replication cohort: P=0.046), rs16944 in IL1B gene (AA: 50% of recanalization, G-carriers: 32%; P=0.038; replication cohort: P=0.049), and rs1063856 in the vWF gene (GG: 53.8% of recanalization, A-carriers: 31.5%; P=0.006; replication cohort: P=0.046). The functional studies revealed an association between the rs1063856 single nucleotide polymorphisms in vWF and FVIII activity (AA: 115.93%, AG: 156.07%, GG: 83.42%; P=0.005). Three single nucleotide polymorphisms were associated with tissue-type plasminogen activator efficacy in the Spanish population, and their mechanism of action might be associated with the activity of coagulation factors.

Regional Variation in Recommended Treatments for Ischemic Stroke and TIA

Secondary stroke prevention treatments vary in different regions of the US. We determined the degree to which guideline-recommended stroke treatments vary by region for patients treated at hospitals participating in a voluntary national quality improvement program, Get with ehe Guidelines--Stroke. Receipt of 8 guideline-recommended treatments (intravenous tissue-type plasminogen activator, antihypertensives, antithrombotics, anticoagulants for atrial fibrillation, deep vein thrombosis prophylaxis, lipid-lowering medications at discharge, smoking cessation counseling, weight loss education) and defect-free care were compared in 4 US regions among eligible patients with ischemic stroke and transient ischemic attack; there was adjustment for patient demographics, medical history, and hospital characteristics. Among 991 995 admissions (South, 37%; Northeast, 27.6%; Midwest, 19.3%; West, 15.9%). Receipt varied regionally for tissue-type plasminogen activator (58.2%-67.8%), lipid-lowering medications (72.5%-75.7%), antihypertensives (80.1%-83.6%), antithrombotics (95.6%-96.8%), deep vein thrombosis prophylaxis (88.0%-91.4%), weight loss education (49.3%-54.7%), and defect-free care (72.1%-76.5%). In adjusted analyses, patients in the South had lower odds of use of intravenous tissue-type plasminogen activator (OR [95% CI]; 0.82 [0.69-0.97]), antihypertensives (0.82 [0.67-0.99]), and defect-free care (0.83 [0.75-0.92]); but, they were more likely to receive lipid-lowering medications (1.28 [1.05-1.54]) compared with those in the Northeast. Patients in the Midwest had lower odds of intravenous tissue-type plasminogen activator administration (0.82 [0.68-0.99]) and defect-free care (0.81 [0.72-0.92]). Those in the West had lower odds of antihypertensives (0.81 [0.67-0.99]), but had greater odds of receiving lipid-lowering medications (1.26 [1.03-1.53]). Despite relatively high rates of adherence to stroke-related therapies in Get With The Guidelines-Stroke hospitals, regional variations exist, with over one quarter of patients receiving suboptimal care. Systematic improvements may lead to better patient outcomes.

Letter by Freeman et al Regarding Article, “Using Dabigatran in Patients With Stroke: A Practical Guide for Clinicians”

To the Editor: We read with great interest the article by Alberts et al1 on “Using Dabigatran in Patients With Stroke: A Practical Guide for Clinicians.” The authors provided an excellent review on dabigatran and the issues encountered in patients with stroke. One challenge with dabigatran is the treatment of acute ischemic stroke for which intravenous tissue-type plasminogen activator administration or endovascular cerebral intervention may be warranted. We recently had a 66-year-old female patient who had been taking 150 mg dabigatran orally twice daily for prevention of stroke in atrial fibrillation. Dabigatran was held 3 days before a cardiac ablation procedure but was resumed immediately after the ablation. Within 1 hour of the procedure, she developed an acute ischemic stroke of the right middle cerebral artery M1 artery on CT angiogram, which resulted in global aphasia …

The Safety of Intravenous Thrombolysis for Ischemic Stroke in Patients With Pre-Existing Cerebral Aneurysms

Unruptured cerebral aneurysms are currently considered a contraindication to intravenous tissue-type plasminogen activator for acute ischemic stroke. This is due to a theoretical increase in the risk of hemorrhage from aneurysm rupture, although it is unknown whether this risk is a significant one. We sought to determine the safety of intravenous tissue-type plasminogen activator administration in a cohort of patients with pre-existing aneurysms. We reviewed the medical records of patients treated for acute ischemic stroke with intravenous tissue-type plasminogen activator during an 11-year period at 2 academic medical centers. We identified a subset of patients with unruptured cerebral aneurysms present on prethrombolysis vascular imaging. Our outcomes of interest were any intracranial hemorrhage, symptomatic intracranial hemorrhage, and subarachnoid hemorrhage. Fisher exact test was used to compare the rates of hemorrhage among patients with and without aneurysms. We identified 236 eligible patients, of whom 22 had unruptured cerebral aneurysms. The rate of intracranial hemorrhage among patients with aneurysms (14%; 95% CI, 3%-35%) did not significantly differ from the rate among patients without aneurysms (19%; 95% CI, 14%-25%). None of the patients with aneurysms developed symptomatic intracranial hemorrhage (0%; 95% CI, 0%-15%) compared with 10 of 214 patients without aneurysms (5%; 95% CI, 2%-8%). Similar proportions of patients developed subarachnoid hemorrhage (5%; 95% CI, 0%-23% versus 6%; 95% CI, 3%-10%). Our findings suggest that intravenous tissue-type plasminogen activator for acute ischemic stroke is safe to administer in patients with pre-existing cerebral aneurysms because the risk of aneurysm rupture and symptomatic intracranial hemorrhage is low.

Effect of the small molecule plasminogen activator inhibitor-1 (PAI-1) inhibitor, PAI-749, in clinical models of fibrinolysis.

The principal inhibitor of fibrinolysis in vivo is plasminogen activator inhibitor-1 (PAI-1). PAI-749 is a small molecule inhibitor of PAI-1 with proven antithrombotic efficacy in several preclinical models. To assess the effect of PAI-749, by using an established ex vivo clinical model of thrombosis and a range of complementary in vitro human plasma-based and whole blood-based models of fibrinolysis. In a double-blind, randomized, crossover study, ex vivo thrombus formation was assessed using the Badimon chamber in 12 healthy volunteers during extracorporeal administration of tissue-type plasminogen activator (t-PA) in the presence of PAI-749 or control. t-PA-mediated lysis of plasma clots and of whole blood model thrombi were assessed in vitro. The role of vitronectin was examined by assessing lysis of fibrin clots generated from purified plasma proteins. There was a dose-dependent reduction in ex vivo thrombus formation by t-PA (P < 0.0001). PAI-749 had no effect on in vitro or ex vivo thrombus formation or fibrinolysis in the presence or absence of t-PA. Inhibition of PAI-1 with a blocking antibody enhanced fibrinolysis in vitro (P < 0.05). Despite its efficacy in a purified human system and in preclinical models of thrombosis, the current study suggests that PAI-749 does not affect thrombus formation or fibrinolysis in a range of established human plasma and whole blood-based systems.

The Plasminogen Fibrinolytic Pathway Is Required for Hematopoietic Regeneration

Hematopoietic stem cells within the bone marrow exist in a quiescent state. They can differentiate and proliferate in response to hematopoietic stress (e.g., myelosuppression), thereby ensuring a well-regulated supply of mature and immature hematopoietic cells within the circulation. However, little is known about how this stress response is coordinated. Here, we show that plasminogen (Plg), a classical fibrinolytic factor, is a key player in controlling this stress response. Deletion of Plg in mice prevented hematopoietic stem cells from entering the cell cycle and undergoing multilineage differentiation after myelosuppression, leading to the death of the mice. Activation of Plg by administration of tissue-type plasminogen activator promoted matrix metalloproteinase-mediated release of Kit ligand from stromal cells, thereby promoting hematopoietic progenitor cell proliferation and differentiation. Thus, activation of the fibrinolytic cascade is a critical step in regulating the hematopoietic stress response.

Infarctus cérébral : stratégie de prise en charge précoce et de reperfusion en urgence

Cerebro-vascular diseases are a leading cause of death and disability worldwide. Their incidence is estimated near 120000 patients in France. Patients with ischemic or hemorrhagic stroke should receive specific management in dedicated stroke units by dedicated stroke teams because of a significant reduction of mortality and institutionalization. Since the results of the National Institute of Neurological Disorders and Stroke trial in 1995, showing a substantial benefit of early administration of tissue-type plasminogen activator no later than 180 minutes after onset of neurological symptoms, specific guidelines have been published for the routine use of this thrombolytic agent in patients with acute ischemic stroke. However the approach of the early recanalisation in acute ischemic stroke has changed since the advent of modern brain imaging including diffusion and perfusion imaging and magnetic resonance angiography. These modern techniques should allow the use of tPA even after the 3 hours time window with a reduced risk of symptomatic brain hemorrhages. In the future, new thrombolytic agents such as desmoteplase or mechanical clots retrieval devices may be used to reperfuse the ischemic tissues in a larger time window from stroke onset and with fewer safety concerns.

Experimental study of intracisternal administration of tissue-type plasminogen activator followed by cerebrospinal fluid drainage in the ultra-early stage of subarachnoid haemorrhage.

This experimental study evaluated the effect of intrathecal injection of tissue-type plasminogen activator followed by cisternal drainage in the ultra-early stage of aneurysmal subarachnoid haemorrhage to prevent vasospasm. Twenty Japanese white rabbits were divided into five groups. Either tPA (groups A, B, and E) or saline (groups C and D) was injected intrathecally 1 hour (groups A, B, C, and D) or 21 hours (group E) after the intrathecal injection of blood. Cerebrospinal fluid was drained 2, 4, and 6 hours after the intrathecal injection of blood (groups A, C, and E). On day 4, the angiographic caliber of the basilar artery in each group was as follows (mean +/- SD): A, 85.9 +/- 5.0%; B, 74.6 +/- 5.3%; C, 69.1 +/- 2.7%; D, 64.0 +/- 4.9%; E, 80.2 +/- 2.7% (compared with baseline). In the two groups in which CSF was drained (groups A and C), fibrinolysis with tPA significantly suppressed vasospasm. In the two groups treated with tPA (groups A and B), cisternal drainage significantly suppressed vasospasm. In the two groups treated with saline (groups C and D), however, cisternal drainage did not suppress vasospasm. Examination of the series of CSF samples (groups A and C) showed that fibrinolysis with tPA effectively cleared clots early. In the two groups treated with tPA and CSF drainage (groups A and E), early removal of subarachnoid clots reduced the degree of vasospasm. Early fibrinolysis with tPA and early removal of subarachnoid clots by drainage is effective for preventing vasospasm.

Fibrinolytic treatment of intraventricular haemorrhage preceding surgical repair of ruptured aneurysms and arteriovenous malformations

Previous studies have indicated that intraventricular administration of tissue-type plasminogen activator (TPA) might improve the prognosis of patients with intraventricular haemorrhage (IVH). In aneurysmal IVH, fibrinolytic treatment was always preceded by surgical repair of the aneurysm, since the risk of recurrent haemorrhage from a non-occluded aneurysm was estimated to be high. We reviewed a series of patients with IVH secondary to ruptured aneurysms (n = 4) or arteriovenous malformation (AVM; n = 1) who underwent emergency intraventricular administration of TPA before repair of the bleeding source. Fibrinolysis resulted in rapid decrease of haematoma volume and of ventricular dilatation, and prevented ventricular catheters from becoming obstructed. No intracranial haemorrhages or other complications occurred.The results suggest that the presence of recently ruptured aneurysms or AVM is not necessarily a contraindication for intraventricular administration of TPA. The potentially life saving benefits might outweigh the inherent risks of recurrent haemorrhage in carefully selected patients with massive IVH, in whom ventricular distension, periventricular brain compression, obstruction of CSF flow, and elevated ICP appear to be major determinants for the outcome.

Comparison of Primary Coronary Angioplasty and Intravenous Thrombolytic Therapy for Acute Myocardial Infarction

To provide a quantitative review of the treatment effects of primary coronary angioplasty vs intravenous thrombolysis for acute myocardial infarction. Ten randomized trials were identified through computerized bibliographic search of MEDLINE from January 1985 through March 1996 and by queries of principal investigators. Single-center and multicenter randomized trials comparing primary angioplasty with intravenous thrombolytic therapy among 2606 patients were included. Four trials compared angioplasty with streptokinase, 3 compared angioplasty with a 3- to 4-hour infusion of tissue-type plasminogen activator, and 3 compared angioplasty with "accelerated" administration of tissue-type plasminogen activator over 90 minutes. Each investigator provided definitions and exact data for outcome events. Odds ratios (ORs), 95% confidence intervals (CIs), and P values were calculated using exact tests for categorical data. Mortality at 30 days or less was 4.4% for the 1290 patients treated with primary angioplasty compared with 6.5% for the 1316 patients treated with thrombolysis (34% reduction; OR, 0.66; 95% CI, 0.46-0.94; P=.02). The effect was similar among thrombolytic regimens, and no subgroup demonstrated a significant reduction in death. The rates of death or nonfatal reinfarction were 7.2% for angioplasty and 11.9% for thrombolytic therapy (OR, 0.58; 95% CI, 0.44-0.76; P<.001). Angioplasty was associated with a significant reduction in total stroke (0.7% vs 2.0%; P=.007) and hemorrhagic stroke (0.1% vs 1.1%; P<.001). Based on outcomes at hospital discharge or 30 days, primary angioplasty appears to be superior to thrombolytic therapy for treatment of patients with acute myocardial infarction, with the proviso that success rates for angioplasty are as good as those achieved in these trials. Data evaluating longer-term outcomes, operator experience, and time delay before treatment are needed before primary angioplasty can be universally recommended as the preferred treatment.