Thrombolysis or anticoagulation for cerebral venous thrombosis: rationale and design of the TO-ACT trial.

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. 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. 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. 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. 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.

Coutinho JM ，Ferro JM ，Zuurbier SM ，Mink MS ，Canhão P ，Crassard I ，Majoie CB ，Reekers JA ，Houdart E ，de Haan RJ ，Bousser MG ，Stam J ... -  《-》

Cerebral venous congestion as indication for thrombolytic treatment.

Tsai FY ，Kostanian V ，Rivera M ，Lee KW ，Chen CC ，Nguyen TH ... -  《CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY》

Effect of Endovascular Treatment With Medical Management vs Standard Care on Severe Cerebral Venous Thrombosis: The TO-ACT Randomized Clinical Trial.

Coutinho JM ，Zuurbier SM ，Bousser MG ，Ji X ，Canhão P ，Roos YB ，Crassard I ，Nunes AP ，Uyttenboogaart M ，Chen J ，Emmer BJ ，Roosendaal SD ，Houdart E ，Reekers JA ，van den Berg R ，de Haan RJ ，Majoie CB ，Ferro JM ，Stam J ，TO-ACT investigators ... -  《-》

Systemic thrombolysis for cerebral venous and dural sinus thrombosis: a systematic review.

The use of thrombolytics is frequently considered in patients with cerebral venous and dural sinus thrombosis (CVT) who deteriorate despite anticoagulant therapy. To collect all the published information about the use of systemic thrombolysis in CVT in order to assess its efficacy and safety. We performed a PubMed search, checked all reference lists of studies found and used data from the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Outcome was classified at the last available follow-up by the modified Rankin Scale (mRS). The cases were stratified according to variables that might influence outcome. A total of 16 reports (26 patients, 2 from the ISCVT and 24 from the systematic review of the literature) were included. No randomized clinical trial was found. Seven patients presented with isolated intracranial hypertension syndrome (26.9%), 17 with encephalopathy (65.4%) and 2 were comatose (7.7%). The superior sagittal sinus was the one most often affected (n = 21; 80.8%), and there was thrombosis of the deep cerebral venous system in 5 patients (19.2%). Urokinase was the thrombolytic agent most frequently administered (n = 19; 73.1%), whereas streptokinase and recombinant tissue plasminogen activator were used in 2 cases each (7.7%). Intracranial hemorrhages occurred in 3 cases (11.5%). Extracranial hemorrhages occurred in 5 cases (19.2%), and overall there were 3 cases of serious bleeding (11.5%), including 2 deaths (7.7%). Partial or complete recanalization was verified in most patients (n = 16; 61.5%). The survival rate was 92.3% (24/26 patients). At the last available follow-up, 22/25 patients regained independency (mRS scores 0-2; 88%), 2/25 died (mRS score 6; 8%) and 1/25 was severely dependent (mRS scores 3-5; 4%). In all, 88% of the CVT patients treated with systemic thrombolysis regained their independency, but 2 deaths associated with intracranial hemorrhage occurred. The mortality rate and disability at the last available follow-up were similar to those found in 2 previous systematic reviews concerning the use of thrombolytics in CVT. Due to the small sample size and lack of controls, the efficacy of systemic thrombolysis in acute CVT cannot be assessed from the published information. Concerning safety, a nonnegligible proportion of bleedings was reported.

Viegas LD ，Stolz E ，Canhão P ，Ferro JM ... -  《-》

Endovascular thrombectomy and thrombolysis for severe cerebral sinus thrombosis: a prospective study.

Stam J ，Majoie CB ，van Delden OM ，van Lienden KP ，Reekers JA ... -  《-》