In the article, there is a spelling mistake of second author's name, and they want to change to G... more In the article, there is a spelling mistake of second author's name, and they want to change to Galia Tsarfati from Galia Tsarfaty. We apologize for any inconvenience that this may have caused.
Introduction Antiphospholipid syndrome (APS) is an autoimmune disorder manifested by thromboembol... more Introduction Antiphospholipid syndrome (APS) is an autoimmune disorder manifested by thromboembolic events, recurrent spontaneous abortions and elevated titers of circulating antiphospholipid antibodies. In addition, the presence of antiphospholipid antibodies seems to confer a fivefold higher risk for stroke or transient ischemic attack. Although the major antigen of APS is β2 glycoprotein I, it is now well established that antiphospholipid antibodies are heterogeneous and bind to various targets. Recently, antibodies to Annexin A2 (ANXA2) have been reported in APS. This is of special interest since data indicated ANXA2 as a key player in fibrinolysis. Therefore, in the present study we assessed whether anti-ANXA2 antibodies play a pathological role in thrombosis associated disease. Materials and Methods Mice were induced to produce anti-ANXA2 antibodies by immunization with ANXA2 (iANXA2) and control mice were immunized with adjuvant only. A middle cerebral artery occlusion stroke...
Background and Aims: Patients with emergent large-vessel occlusion (ELVO) that present earlier th... more Background and Aims: Patients with emergent large-vessel occlusion (ELVO) that present earlier than 4 h from onset are usually treated with bridging systemic thrombolysis followed by endovascular thrombectomy (EVT). Whether direct EVT (dEVT) could improve the chances of favorable outcome remains unknown. Methods: Consecutively, prospectively enrolled patients with ELVO presenting within 4 h of onset were entered into a National Acute Stroke Registry of patients undergoing revascularization. Patients treated with bridging were compared to those treated with dEVT. Excellent outcome was defined as having a modified Rankin Scale score ≤1 at 90 days following stroke. Results: Out of 392 patients that underwent thrombectomy, 270 (68%) presented within 4 h and were included. Of those, 159 (59%) underwent bridging and 111 (41%) underwent dEVT. Atrial fibrillation and congestive heart failure were more common in the dEVT group (43 vs. 30%, p = 0.04 and 20 vs. 8%, p = 0.009, respectively), but other risk factors, demographics, stroke severity and subtypes as well as baseline vessel patency state and time metrics did not differ. Excellent target vessel recanalization defined as TICI 3 (thrombolysis in cerebral infarction score) was more common in the dEVT group (75 vs. 61%, p = 0.03), but in-hospital mortality, discharge destinations, short-and long-term excellent outcome rates did not differ. On multivariate regression analysis, treatment modality did
Introduction: Systemic Thrombolysis with tissue Plasminogen Activator (tPA) has been an establish... more Introduction: Systemic Thrombolysis with tissue Plasminogen Activator (tPA) has been an established therapy for ischemic stroke for more than 20 years, with limited effect on large vessel occlusions. New catheter-based techniques allow high revascularization rates were tPA fails. Systemic thrombolysis remains the standard treatment of care and endovascular treatment is newly established as therapy for large vessel occlusion or rescue therapy after unsuccessful revascularization by thrombolysis. Patients with large vessel occlusions have a very limited reperfusion rate and benefit from direct endovascular treatment (EVT). In this real-life study, patients are compared regarding their outcome after systemic thrombolysis with rescue endovascular treatment in comparison to direct endovascular treatment for large vessel occlusions. Patients and Methods: Patients are categorized retrospectively by their treatment. Data on 120 patients was used, with the exclusion of 13 patients. Analyses were performed according to mRS and EQ5D after 7 days as well as 10 to 14 weeks. Primary observed outcome was quality of life and mRS after 10 to 14 weeks. Results: Regarding mRS, initial outcome after 7 days is more successful with direct EVT, but prior thrombolysis shows additional improvement after 10 to 14 weeks. There is no statistically relevant difference in patients that received prior tPA and rescue endovascular treatment in comparison to direct endovascular treatment after 10 to 14 weeks. EQ5D on the other hand shows higher life quality, according to better functional outcome after endovascular treatment. Regarding the primary endpoint of the study, there is no statistically relevant difference between both study groups at the end point of the study. Discussion: While direct endovascular treatment shows an immediate benefit for patients with large vessel occlusions, over the time course of 10 to 14 weeks there is a higher additional benefit for prior thrombolysis treatment. Regarding that, both treatment arms show a similar outcome. A higher life quality regarding EQ5D is archived after direct EVT while judgement for general ability is rated higher with additional tPA treatment. Conclusion: In this mono-center study it was shown that patients eligible for thrombolysis with large vessel occlusions should receive tPA if eligible. By lack or insufficient improvement, a rescue endovascular treatment should be applied. Direct endovascular treatment shows a similar outcome regarding mRS but a higher life quality index.
Background Many patients with large vessel occlusion (LVO) who are otherwise candidates for endov... more Background Many patients with large vessel occlusion (LVO) who are otherwise candidates for endovascular treatment (EVT) have had previous strokes. We aimed to examine the effect of previous stroke on outcome after EVT. Methods Consecutive patients with LVO were prospectively entered into a National Acute Stroke registry of patients undergoing EVT. Patients treated with EVT were divided into those with and without previous strokes. The rates of favorable reperfusion status, mortality, and excellent outcome at 90 days post-stroke as well as symptomatic intracranial hemorrhage (sICH) were evaluated. Results A total of 390 underwent EVT and 35 had previous strokes. Patients with previous strokes were significantly older; more frequently had a history of prior myocardial infarction and more often had pre-existing functional disability. Favorable target vessel recanalization was less frequently achieved in patients with previous strokes (60% vs. 82%; p = 0.005) and ordinal regression ana...
Journal of neurointerventional surgery, Jan 30, 2017
The region defined as 'at risk' penumbra by current CT perfusion (CTP) maps is largely ov... more The region defined as 'at risk' penumbra by current CT perfusion (CTP) maps is largely overestimated. We aimed to quantitate the portion of true 'at risk' tissue within CTP penumbra and to determine the parameter and threshold that would optimally distinguish it from false 'at risk' tissue, that is, benign oligaemia. Among acute stroke patients evaluated by multimodal CT (NCCT/CTA/CTP) we identified those that had not undergone endovascular/thrombolytic treatment and had follow-up NCCT. Maps of absolute and relative CBF, CBV, MTT, TTP and Tmax as well as summary maps depicting infarcted and penumbral regions were generated using the Intellispace Portal (Philips Healthcare, Best, Netherlands). Follow-up CT was automatically co-registered to the CTP scan and the final infarct region was manually outlined. Perfusion parameters were systematically analysed - the parameter that resulted in the highest true-negative-rate (ie, proportion of benign oligaemia correctl...
Despite overwhelming evidence for the benefits of anticoagulation in patients with brain ischemia... more Despite overwhelming evidence for the benefits of anticoagulation in patients with brain ischemia and atrial fibrillation, vast underuse has been reported. Use of anticoagulation for secondary stroke prevention was assessed in the National Acute Stroke Israeli Survey registry (NASIS) of hospitalized patients with atrial fibrillation and acute brain ischemia. Logistic regression analysis was performed to evaluate the effects of clinical covariates on anticoagulation therapy at discharge, and anticoagulation use over time was assessed in subgroups of patients with identified barriers to anticoagulation utilization. There were 1254 survivors of acute brain ischemia with atrial fibrillation (mean age 77.2±10.6 years; 57.7% female). Between 2004 and 2013, the proportion of patients discharged on anticoagulation increased from 55% to 76.2%, and among those without perceived contraindications from 70% to 96% (P<0.0001). Older age, greater stroke severity, earlier registry period, and pr...
Rapid restoration of cerebral blood flow is the principle goal of acute ischemic stroke therapy. ... more Rapid restoration of cerebral blood flow is the principle goal of acute ischemic stroke therapy. Intravenous recombinant tissue plasminogen activator is an effective therapy for acute ischemic stroke. It has been available in the United States for over a decade and was approved for use in Israel at the end of 2004. To assess the implementation of intravenous rt-PA in routine clinical care at our center after its formal approval in Israel, and the therapeutic and logistic implications for reperfusion therapy for acute ischemic stroke in Israel. Patients with acute ischemic stroke admitted between January 2005 and June 2006 who were treated with intravenous rt-PA or endovascular-based reperfusion were reviewed. Implementation, timing, safety and clinical outcomes were assessed. Forty-six patients received reperfusion therapy (37 with intravenous rt-PA and 9 with endovascular-based therapy), corresponding to 4.0% of ischemic stroke patients in 2005 and a projection of 6.2% in 2006. The...
Endovascular intraarterial (IA) strategies have emerged as important treatment options for patien... more Endovascular intraarterial (IA) strategies have emerged as important treatment options for patients with acute ischemic stroke who are ineligible for intravenous (IV) tissue plasminogen activator (tPA) or in whom such therapy has failed. The goal of this article is to provide a comprehensive review of percutaneous IA endovascular techniques aimed at revascularization in the setting of acute ischemic stroke from IA thrombolysis, mechanical thrombectomy, and primary intracranial stenting to retrievable-stent technology. For each modality, we focus on the existing clinical data, including our institutional experience and techniques.
In the article, there is a spelling mistake of second author's name, and they want to change to G... more In the article, there is a spelling mistake of second author's name, and they want to change to Galia Tsarfati from Galia Tsarfaty. We apologize for any inconvenience that this may have caused.
Introduction Antiphospholipid syndrome (APS) is an autoimmune disorder manifested by thromboembol... more Introduction Antiphospholipid syndrome (APS) is an autoimmune disorder manifested by thromboembolic events, recurrent spontaneous abortions and elevated titers of circulating antiphospholipid antibodies. In addition, the presence of antiphospholipid antibodies seems to confer a fivefold higher risk for stroke or transient ischemic attack. Although the major antigen of APS is β2 glycoprotein I, it is now well established that antiphospholipid antibodies are heterogeneous and bind to various targets. Recently, antibodies to Annexin A2 (ANXA2) have been reported in APS. This is of special interest since data indicated ANXA2 as a key player in fibrinolysis. Therefore, in the present study we assessed whether anti-ANXA2 antibodies play a pathological role in thrombosis associated disease. Materials and Methods Mice were induced to produce anti-ANXA2 antibodies by immunization with ANXA2 (iANXA2) and control mice were immunized with adjuvant only. A middle cerebral artery occlusion stroke...
Background and Aims: Patients with emergent large-vessel occlusion (ELVO) that present earlier th... more Background and Aims: Patients with emergent large-vessel occlusion (ELVO) that present earlier than 4 h from onset are usually treated with bridging systemic thrombolysis followed by endovascular thrombectomy (EVT). Whether direct EVT (dEVT) could improve the chances of favorable outcome remains unknown. Methods: Consecutively, prospectively enrolled patients with ELVO presenting within 4 h of onset were entered into a National Acute Stroke Registry of patients undergoing revascularization. Patients treated with bridging were compared to those treated with dEVT. Excellent outcome was defined as having a modified Rankin Scale score ≤1 at 90 days following stroke. Results: Out of 392 patients that underwent thrombectomy, 270 (68%) presented within 4 h and were included. Of those, 159 (59%) underwent bridging and 111 (41%) underwent dEVT. Atrial fibrillation and congestive heart failure were more common in the dEVT group (43 vs. 30%, p = 0.04 and 20 vs. 8%, p = 0.009, respectively), but other risk factors, demographics, stroke severity and subtypes as well as baseline vessel patency state and time metrics did not differ. Excellent target vessel recanalization defined as TICI 3 (thrombolysis in cerebral infarction score) was more common in the dEVT group (75 vs. 61%, p = 0.03), but in-hospital mortality, discharge destinations, short-and long-term excellent outcome rates did not differ. On multivariate regression analysis, treatment modality did
Introduction: Systemic Thrombolysis with tissue Plasminogen Activator (tPA) has been an establish... more Introduction: Systemic Thrombolysis with tissue Plasminogen Activator (tPA) has been an established therapy for ischemic stroke for more than 20 years, with limited effect on large vessel occlusions. New catheter-based techniques allow high revascularization rates were tPA fails. Systemic thrombolysis remains the standard treatment of care and endovascular treatment is newly established as therapy for large vessel occlusion or rescue therapy after unsuccessful revascularization by thrombolysis. Patients with large vessel occlusions have a very limited reperfusion rate and benefit from direct endovascular treatment (EVT). In this real-life study, patients are compared regarding their outcome after systemic thrombolysis with rescue endovascular treatment in comparison to direct endovascular treatment for large vessel occlusions. Patients and Methods: Patients are categorized retrospectively by their treatment. Data on 120 patients was used, with the exclusion of 13 patients. Analyses were performed according to mRS and EQ5D after 7 days as well as 10 to 14 weeks. Primary observed outcome was quality of life and mRS after 10 to 14 weeks. Results: Regarding mRS, initial outcome after 7 days is more successful with direct EVT, but prior thrombolysis shows additional improvement after 10 to 14 weeks. There is no statistically relevant difference in patients that received prior tPA and rescue endovascular treatment in comparison to direct endovascular treatment after 10 to 14 weeks. EQ5D on the other hand shows higher life quality, according to better functional outcome after endovascular treatment. Regarding the primary endpoint of the study, there is no statistically relevant difference between both study groups at the end point of the study. Discussion: While direct endovascular treatment shows an immediate benefit for patients with large vessel occlusions, over the time course of 10 to 14 weeks there is a higher additional benefit for prior thrombolysis treatment. Regarding that, both treatment arms show a similar outcome. A higher life quality regarding EQ5D is archived after direct EVT while judgement for general ability is rated higher with additional tPA treatment. Conclusion: In this mono-center study it was shown that patients eligible for thrombolysis with large vessel occlusions should receive tPA if eligible. By lack or insufficient improvement, a rescue endovascular treatment should be applied. Direct endovascular treatment shows a similar outcome regarding mRS but a higher life quality index.
Background Many patients with large vessel occlusion (LVO) who are otherwise candidates for endov... more Background Many patients with large vessel occlusion (LVO) who are otherwise candidates for endovascular treatment (EVT) have had previous strokes. We aimed to examine the effect of previous stroke on outcome after EVT. Methods Consecutive patients with LVO were prospectively entered into a National Acute Stroke registry of patients undergoing EVT. Patients treated with EVT were divided into those with and without previous strokes. The rates of favorable reperfusion status, mortality, and excellent outcome at 90 days post-stroke as well as symptomatic intracranial hemorrhage (sICH) were evaluated. Results A total of 390 underwent EVT and 35 had previous strokes. Patients with previous strokes were significantly older; more frequently had a history of prior myocardial infarction and more often had pre-existing functional disability. Favorable target vessel recanalization was less frequently achieved in patients with previous strokes (60% vs. 82%; p = 0.005) and ordinal regression ana...
Journal of neurointerventional surgery, Jan 30, 2017
The region defined as 'at risk' penumbra by current CT perfusion (CTP) maps is largely ov... more The region defined as 'at risk' penumbra by current CT perfusion (CTP) maps is largely overestimated. We aimed to quantitate the portion of true 'at risk' tissue within CTP penumbra and to determine the parameter and threshold that would optimally distinguish it from false 'at risk' tissue, that is, benign oligaemia. Among acute stroke patients evaluated by multimodal CT (NCCT/CTA/CTP) we identified those that had not undergone endovascular/thrombolytic treatment and had follow-up NCCT. Maps of absolute and relative CBF, CBV, MTT, TTP and Tmax as well as summary maps depicting infarcted and penumbral regions were generated using the Intellispace Portal (Philips Healthcare, Best, Netherlands). Follow-up CT was automatically co-registered to the CTP scan and the final infarct region was manually outlined. Perfusion parameters were systematically analysed - the parameter that resulted in the highest true-negative-rate (ie, proportion of benign oligaemia correctl...
Despite overwhelming evidence for the benefits of anticoagulation in patients with brain ischemia... more Despite overwhelming evidence for the benefits of anticoagulation in patients with brain ischemia and atrial fibrillation, vast underuse has been reported. Use of anticoagulation for secondary stroke prevention was assessed in the National Acute Stroke Israeli Survey registry (NASIS) of hospitalized patients with atrial fibrillation and acute brain ischemia. Logistic regression analysis was performed to evaluate the effects of clinical covariates on anticoagulation therapy at discharge, and anticoagulation use over time was assessed in subgroups of patients with identified barriers to anticoagulation utilization. There were 1254 survivors of acute brain ischemia with atrial fibrillation (mean age 77.2±10.6 years; 57.7% female). Between 2004 and 2013, the proportion of patients discharged on anticoagulation increased from 55% to 76.2%, and among those without perceived contraindications from 70% to 96% (P<0.0001). Older age, greater stroke severity, earlier registry period, and pr...
Rapid restoration of cerebral blood flow is the principle goal of acute ischemic stroke therapy. ... more Rapid restoration of cerebral blood flow is the principle goal of acute ischemic stroke therapy. Intravenous recombinant tissue plasminogen activator is an effective therapy for acute ischemic stroke. It has been available in the United States for over a decade and was approved for use in Israel at the end of 2004. To assess the implementation of intravenous rt-PA in routine clinical care at our center after its formal approval in Israel, and the therapeutic and logistic implications for reperfusion therapy for acute ischemic stroke in Israel. Patients with acute ischemic stroke admitted between January 2005 and June 2006 who were treated with intravenous rt-PA or endovascular-based reperfusion were reviewed. Implementation, timing, safety and clinical outcomes were assessed. Forty-six patients received reperfusion therapy (37 with intravenous rt-PA and 9 with endovascular-based therapy), corresponding to 4.0% of ischemic stroke patients in 2005 and a projection of 6.2% in 2006. The...
Endovascular intraarterial (IA) strategies have emerged as important treatment options for patien... more Endovascular intraarterial (IA) strategies have emerged as important treatment options for patients with acute ischemic stroke who are ineligible for intravenous (IV) tissue plasminogen activator (tPA) or in whom such therapy has failed. The goal of this article is to provide a comprehensive review of percutaneous IA endovascular techniques aimed at revascularization in the setting of acute ischemic stroke from IA thrombolysis, mechanical thrombectomy, and primary intracranial stenting to retrievable-stent technology. For each modality, we focus on the existing clinical data, including our institutional experience and techniques.
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Papers by David Orion