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Small retrospective studies have shown the benefit of endovascular treatment with intrasinus thrombolysis (IST) or mechanical thrombectomy (MT) with/without IST (MT ± IST) in cases of multifocal cerebral venous thrombosis (CVT). Our study compares the mortality, functional outcome and periprocedural complications among patients treated with MT ± IST versus IST alone. We reviewed clinical and angiographic findings of 63 patients with CVT who received endovascular treatment at three tertiary care centers. Primary outcome variables were discharge mortality and neurological dysfunction, and intermediate (three months) and long-term (>six months) morbidity. The modified Rankin scale (mRS) was used to assess morbidity. mRS ≤ 1 was considered a good recovery. Neurological dysfunction was rated as neuroscore: 0, normal; 1, mild (ambulatory, communicative); 2, moderate (non-ambulatory, communicative); and 3, severe (non-ambulatory, non-communicative/comatose). In patients who received IST alone, presenting neurological deficits were comparatively minor (p<0.001). When the two groups were adjusted for admission neuroscore, there was no statistical significance between discharge mortality [7(21%) versus 4(14%), p=0.228], neurological dysfunction (p=0.442), intermediate (p=0.336) and long-term morbidity (p=0.988). Patients who received MT ± IST had a higher percentage of periprocedural complications without reaching statistical significance. Compared to IST, MT was performed in severe cases with extensive sinus involvement. When adjusted for admission neurological dysfunction, both groups had similar mortality and discharge neurological dysfunction and similar intermediate and long-term morbidity.

Rationale: Endovascular thrombolysis, with or without mechanical clot removal, may be beneficial for a subgroup of patients with cerebral venous sinus thrombosis (CVT) who have a poor prognosis despite treatment with heparin. Published experience with endovascular thrombolysis is promising but only based on case series and not on controlled trials., Aim: The objective of the Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis (TO-ACT) trial is to determine if endovascular thrombolysis improves the functional outcome of patients with a severe form of CVT., Design: The TO-A C T trial is a multicenter, prospective, randomized, open-label, blinded endpoint trial. Patients are eligible if they have a radiologically proven CVT, a high probability of poor outcome (defined by presence of one or more of the following risk factors: mental status disorder, coma, intracranial hemorrhagic lesion, or thrombosis of the deep cerebral venous system), and if the responsible physician is uncertain if endovascular thrombolysis or standard anticoagulant treatment is better. One hundred sixty-four patients (82 in each treatment arm) will be included to detect a 50% relative reduction (from 40% to 20%) of poor outcomes., Study: Patients will be randomized to receive either endovascular thrombolysis or standard therapy (therapeutic doses of heparin). Endovascular thrombolysis is composed of local application of rt-plasminogen activator (PA) or urokinase within the thrombosed sinuses, mechanical thrombosuction, or a combination of both. Patients randomized to endovascular thrombolysis will be treated with heparin before and after the interventional procedure, according to international guidelines., Outcomes: The primary endpoint is the modified Rankin score (mRS) at 12 months, with a score ≥2 defined as poor outcome. Secondary outcomes are six-months mRS, mortality, and recanalization rate. Major intracranial and extracranial hemorrhagic complications within one-week after the intervention are the principal safety outcomes. Results will be analyzed according to the 'intention-to-treat' principle. Blinded assessors not involved in the treatment of the patient will assess endpoints with standardized questionnaires., (© 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.)

Background: Ethnic differences have been reported with regard to several medical therapies. The aim of this study was to investigate the relation between ethnicity and thrombolysis in stroke patients., Methods: Retrospective single-centre study. Patients admitted with an ischemic stroke between 2003 and 2008 were included. Ethnicity was determined by self-identification and stratified into white and non-white (all other ethnicities). The main outcome measure was the difference in thrombolysis rate between white and non-white patients. Logistic regression analysis was used to identify potential confounders of the relation between ethnicity and thrombolysis., Results: 510 patients were included, 392 (77%) white and 118 (23%) non-white. Non-white patients were younger (median 69 vs. 60 years, p<0.001), had a higher blood pressure at admission (median systolic 150 vs. 160 mmHg, p=0.02) and a lower stroke severity (median NIHSS 5 vs. 4, p=0.04). Non-white patients were significantly less often treated with thrombolysis compared to white patients (odds ratio 0.34, 95% CI 0.17-0.71), which was partly explained by a later arrival at the hospital. After adjustment for potential confounders (late arrival, age, blood pressure above upper limit for thrombolysis, and oral anticoagulation use), a trend towards a lower thrombolysis rate in non-whites remained (adjusted odds ratio 0.38, 95% CI 0.13 to 1.16)., Conclusions: Non-white stroke patients less often received thrombolysis than white patients, partly as a result of a delay in presentation. In this single centre study, potential bias due to hospital differences or insurance status could be ruled out as a cause. The magnitude of the difference is worrisome and requires further investigation. Modifiable causes, such as patient delay, awareness of stroke symptoms, language barriers and treatment of cardiovascular risk factors, should be addressed specifically in these ethnic groups in future stroke campaigns., (© 2011 Coutinho et al; licensee BioMed Central Ltd.)

Background: Thrombolysis with intravenous rt-PA is currently the only approved acute therapy for ischemic stroke. Re-occlusion after initial recanalization occurs in up to 34% in patients treated with rt-PA, probably caused by platelet activation. In acute myocardial infarction, the combination of thrombolysis and antiplatelet therapy leads to a greater reduction of mortality compared to thrombolysis alone. In patients with acute ischemic stroke, several studies showed that patients already on antiplatelet treatment prior to thrombolysis had an equal or even better outcome compared to patients without prior antiplatelet treatment, despite an increased risk of intracerebral bleeding. Based on the fear of intracerebral haemorrhage, current international guidelines recommend postponing antiplatelet therapy until 24 hours after thrombolysis. Remarkably, prior use of antiplatelet therapy is not a contra-indication for thrombolysis. We hypothesize that antiplatelet therapy in combination with rt-PA thrombolysis will improve outcome by enhancing fibrinolysis and preventing re-occlusion., Methods/design: ARTIS is a randomised multi-center controlled trial with blind endpoint assessment. Our objective is to investigate whether immediate addition of aspirin to rt-PA thrombolysis improves functional outcome in ischemic stroke. Patients with acute ischemic stroke eligible for rt-PA thrombolysis are randomised to receive 300 mg aspirin within 1.5 hours after start of thrombolysis or standard care, consisting of antiplatelet therapy after 24 hours. Primary outcome is poor functional health at 3 months follow-up (modified Rankin Scale 3 - 6)., Discussion: This is the first clinical trial investigating the combination of rt-PA and acute aspirin by means of a simple and cheap adjustment of current antiplatelet regimen. We expect the net benefit of improved functional outcome will overcome the possible slightly increased risk of intracerebral haemorrhage., Trial Registration: The Netherlands National Trial Register NTR822. The condensed rationale of the ARTIS-Trial has already been published in Cerebrovascular Diseases.

Background: Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is currently the only approved acute therapy for ischemic stroke. After rt-PA-induced recanalization, reocclusion is observed in 20-34%, probably caused by platelet activation. In acute myocardial infarction, the combination of thrombolytic and antiplatelet therapy leads to a better outcome compared to thrombolytic treatment alone. In patients with acute ischemic stroke, several studies showed that those on antiplatelet treatment prior to rt-PA had an equal or even better outcome compared to patients without prior use of antiplatelet therapy, despite an increased risk of bleeding., Methods: We present the protocol of a multicenter randomized clinical trial (n = 800) investigating the effects of immediate addition of aspirin to rt-PA on poor outcome (modified Rankin score >2) in ischemic stroke patients., Conclusion: This study will answer the question whether the combination of rt-PA and antiplatelet therapy improves the functional outcome in ischemic stroke patients.

In the European Cooperative Acute Stroke Study 3 (ECASS3), the efficacy of intravenous thrombolysis between 3 and 4.5 hours following onset of ischaemic stroke was investigated. Compared to the placebo group, patients treated with intravenous alteplase had a better functional outcome after 3 months (odds ratio 1.34, 95% confidence interval 1.02-1.76). The risk of symptomatic intracerebral haemorrhage was higher in the alteplase group (2.4% versus 0.3%). The time window for intravenous alteplase can be safely extended to 4.5 hours, but efforts should be made to start treatment as soon as possible, since the effectiveness ofalteplase decreases over time.

Background and Purpose: Most patients with cerebral sinus thrombosis (CST) recover after treatment with heparin, but a subgroup has a poor prognosis. Those patients may benefit from endovascular thrombolysis., Methods: Prospective case series. Patients with sinus thrombosis were selected for thrombolysis if they had an altered mental status, coma, straight sinus thrombosis, or large space-occupying lesions. Urokinase was infused into the sinuses (bolus 120 to 600 x 10(3) U; then 100 x 10(3) U/h) via a jugular catheter, in 15 cases combined with mechanical thrombus disruption or removal., Results: We treated 20 patients (16 women), mean age 32 years. Twelve patients were comatose and 14 had hemorrhagic infarcts before thrombolysis. Twelve patients recovered (Rankin score 0 to 2), 2 survived with handicaps, and 6 died. Factors associated with a fatal outcome were leukemia (3/6 versus 0/14, P=0.02) and large hemorrhagic infarcts (4/6 versus 2/14, P=0.04). Seizures were less frequent in the fatal cases (P=0.05). Patients who died had a larger mean lesion surface than survivors (30.5 versus 13.6 cm(2); P=0.03), larger midline shift (5.2 versus 1.7 mm; P=0.02), and a more rapid course (2.7 versus 8.2 days; P=0.01). Five patients who died had large hemispheric infarcts and edema before thrombolysis, causing herniation. Five patients had increased cerebral hemorrhage (3 minor, 2 major) after thrombolysis., Conclusions: Thrombolysis can be effective for severe sinus thrombosis, but patients may deteriorate because of increased cerebral hemorrhage. Patients with large infarcts and impending herniation did not benefit.

Two patients with cerebral sinus thrombosis were successfully treated with neuroradiological intervention procedures, one with local thrombolysis and the other with mechanical thrombosuction using a hydrolyser catheter. The first patient, a 20-year-old woman, was treated with asparaginase for acute lymphatic leukaemia. She lapsed into coma with extensor posturing due to superior sagittal and right transverse sinus thrombosis. She recovered completely after local thrombolysis with 2,940,000 units urokinase, administered over a period of 40 hours. The second patient was a 29-year-old man who presented with clinical deterioration after seizures due to superior sagittal, left transverse and straight sinus thrombosis. A CT-scan demonstrated bilateral haemorrhagic cerebral infarctions. Since the risk of haemorrhage during thrombolysis with urokinase was considered to be high, mechanical thrombosuction with a hydrolyser catheter was performed. This procedure took only 4 hours. The patient recovered completely in two weeks. These cases add further evidence to the effectiveness of thrombolysis and thrombosuction in selected patients with severe cerebral sinus thrombosis.

Thrombolysis by intravenous application of thrombolytic drugs may improve the outcome of patients with a brain infarct, but it also entails risks. The effect of recombinant tissue plasminogen activator (rtPA) was compared with placebo in three medium-sized randomized controlled clinical trials. One study, performed in North America, showed a clear benefit of rtPA administered within 3 hours after the onset of symptoms. Two European trials showed a less strong effect, but the number of patients who were independent after 3 months' follow-up was also larger after treatment with rtPA within 6 hours. A meta-analysis of all three trials demonstrates a significant advantage of rtPA over placebo for all the usual outcome measures, without significant excess mortality in the rtPA group. The chance of being able to live independently increases by about 8% after treatment with rtPA. In conclusion there is now sufficient evidence to start with thrombolytic treatment for cerebral infarcts in hospitals with a stroke unit, if a number of additional quality standards for the acute diagnosis and treatment of stroke patients are met.

Background: Cerebral venous and sinus thrombosis (CVST) is a rather rare disease which accounts for <1% of all strokes. Diagnosis is still frequently overlooked or delayed as a result of the wide spectrum of clinical symptoms and the often subacute or lingering onset. Current therapeutic measures which are used in clinical practice include the use of anticoagulants such as dose-adjusted intravenous heparin or body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH), the use of thrombolysis and symptomatic therapy including control of seizures and elevated intracranial pressure. Methods: We searched MEDLINE (National Library of Medicine), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Library to review the strength of evidence to support these interventions and the preparation of recommendations on the therapy of CVST based on the best available evidence. Review articles and book chapters were also included. Recommendations were reached by consensus. Where there was a lack of evidence but consensus was clear we stated our opinion as good practice points. Results and conclusions: Patients with CVST without contraindications for anticoagulation (AC) should be treated either with body weight-adjusted subcutaneous LMWH or with dose-adjusted intravenous heparin (level B recommendation). Concomitant intracranial haemorrhage (ICH) related to CVST is not a contraindication for heparin therapy. The optimal duration of oral anticoagulant therapy after the acute phase is unclear. Oral AC may be given for 3 months if CVST was secondary to a transient risk factor, for 6–12 months in patients with idiopathic CVST and in those with “mild” thrombophilia, such as heterozygous factor V Leiden or prothrombin G20210A mutation and high plasma levels of factor VIII. Indefinite AC should be considered in patients with recurrent episodes of CVST and in those with one episode of CVST and ‘severe’ thrombophilia, such as antithrombin, protein C or protein S deficiency, homozygous factor V Leiden or prothrombin G20210A mutation, antiphospholipid antibodies and combined abnormalities (good practice point). There is insufficient evidence to support the use of either systemic or local thrombolysis in patients with CVST. If patients deteriorate despite adequate AC and other causes of deterioration have been ruled out, thrombolysis may be a therapeutic option in selected cases, possibly in those without large ICH and threatening herniation (good practice point). There are no controlled data about the risks and benefits of certain therapeutic measures to reduce an elevated intracranial pressure (with brain displacement) in patients with severe CVST. However, in severe cases with impending herniation craniectomy can be used as a life-saving intervention (good practice point). [ABSTRACT FROM AUTHOR]

Cerebral venous and sinus thrombosis (CVST) is a rather rare disease which accounts for <1% of all strokes. Diagnosis is still frequently overlooked or delayed due to the wide spectrum of clinical symptoms and the often subacute or lingering onset. Current therapeutic measures which are used in clinical practice include the use of anticoagulants such as dose-adjusted intravenous heparin or body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH), the use of thrombolysis, and symptomatic therapy including control of seizures and elevated intracranial pressure. We searched MEDLINE (National Library of Medicine), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Library to review the strength of evidence to support these interventions and the preparation of recommendations on the therapy of CVST based on the best available evidence. Review articles and book chapters were also included. Recommendations were reached by consensus. Where there was a lack of evidence, but consensus was clear we stated our opinion as good practice points. Patients with CVST without contraindications for anticoagulation should be treated either with body weight-adjusted subcutaneous LMWH or dose-adjusted intravenous heparin (good practice point). Concomitant intracranial haemorrhage related to CVST is not a contraindication for heparin therapy. The optimal duration of oral anticoagulation after the acute phase is unclear. Oral anticoagulation may be given for 3 months if CVST was secondary to a transient risk factor, for 6–12 months in patients with idiopathic CVST and in those with ‘mild’ hereditary thrombophilia. Indefinite anticoagulation (AC) should be considered in patients with two or more episodes of CVST and in those with one episode of CVST and ‘severe’ hereditary thrombophilia (good practice point). There is insufficient evidence to support the use of either systemic or local thrombolysis in patients with CVST. If patients deteriorate despite adequate anticoagulation and other causes of deterioration have been ruled out, thrombolysis may be a therapeutic option in selected cases, possibly in those without intracranial haemorrhage (good practice point). There are no controlled data about the risks and benefits of certain therapeutic measures to reduce an elevated intracranial pressure (with brain displacement) in patients with severe CVST. Antioedema treatment (including hyperventilation, osmotic diuretics and craniectomy) should be used as life saving interventions (good practice point). [ABSTRACT FROM AUTHOR]

Background: Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is currently the only approved acute therapy for ischemic stroke. After rt-PA-induced recanalization, reocclusion is observed in 20–34%, probably caused by platelet activation. In acute myocardial infarction, the combination of thrombolytic and antiplatelet therapy leads to a better outcome compared to thrombolytic treatment alone. In patients with acute ischemic stroke, several studies showed that those on antiplatelet treatment prior to rt-PA had an equal or even better outcome compared to patients without prior use of antiplatelet therapy, despite an increased risk of bleeding. Methods: We present the protocol of a multicenter randomized clinical trial (n = 800) investigating the effects of immediate addition of aspirin to rt-PA on poor outcome (modified Rankin score >2) in ischemic stroke patients. Conclusion: This study will answer the question whether the combination of rt-PA and antiplatelet therapy improves the functional outcome in ischemic stroke patients. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]