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Background: Intracranial occlusion site, contrast permeability, and clot burden are thrombus characteristics that influence alteplase-associated reperfusion. In this study, we assessed the reperfusion efficacy of tenecteplase and alteplase in subgroups based on these characteristics in a pooled analysis of the EXTEND-IA TNK trial (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke). Methods: Patients with large vessel occlusion were randomized to treatment with tenecteplase (0.25 or 0.4 mg/kg) or alteplase before thrombectomy in hospitals across Australia and New Zealand (2015–2019). The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion on first-pass angiogram. We compared the effect of tenecteplase versus alteplase overall, and in subgroups, based on the following measured with computed tomography angiography: intracranial occlusion site, contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores). We adjusted for covariates using mixed effects logistic regression models. Results: Tenecteplase was associated with higher odds of early reperfusion (75/369 [20%] versus alteplase: 9/96 [9%], adjusted odds ratio [aOR], 2.18 [95% CI, 1.03–4.63]). The difference between thrombolytics was notable in occlusions with low clot burden (tenecteplase: 66/261 [25%] versus alteplase: 5/67 [7%], aOR, 3.93 [95% CI, 1.50–10.33]) when compared to high clot burden lesions (tenecteplase: 9/108 [8%] versus alteplase: 4/29 [14%], aOR, 0.58 [95% CI, 0.16–2.06]; P interaction =0.01). We did not observe an association between contrast permeability and tenecteplase treatment effect (permeability present: aOR, 2.83 [95% CI, 1.00–8.05] versus absent: aOR, 1.98 [95% CI, 0.65–6.03]; P interaction =0.62). Tenecteplase treatment effect was superior with distal M1 or M2 occlusions (53/176 [30%] versus alteplase: 4/42 [10%], aOR, 3.73 [95% CI, 1.25–11.11]), but both thrombolytics had limited efficacy with internal carotid artery occlusions (tenecteplase 1/73 [1%] versus alteplase 1/19 [5%], aOR, 0.22 [95% CI, 0.01–3.83]; P interaction =0.16). Conclusions: Tenecteplase demonstrates superior early reperfusion versus alteplase in lesions with low clot burden. Reperfusion efficacy remains limited in internal carotid artery occlusions and lesions with high clot burden. Further innovation in thrombolytic therapies are required.

The benefit of combined treatment with intravenous thrombolysis before endovascular thrombectomy in patients with acute ischaemic stroke caused by large vessel occlusion remains unclear. We hypothesised that the clinical outcomes of patients with stroke with large vessel occlusion treated with direct endovascular thrombectomy within 4·5 h would be non-inferior compared with the outcomes of those treated with standard bridging therapy (intravenous thrombolysis before endovascular thrombectomy).DIRECT-SAFE was an international, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Adult patients with stroke and large vessel occlusion in the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or basilar artery, confirmed by non-contrast CT and vascular imaging, and who presented within 4·5 h of stroke onset were recruited from 25 acute-care hospitals in Australia, New Zealand, China, and Vietnam. Eligible patients were randomly assigned (1:1) via a web-based, computer-generated randomisation procedure stratified by site of baseline arterial occlusion and by geographic region to direct endovascular thrombectomy or bridging therapy. Patients assigned to bridging therapy received intravenous thrombolytic (alteplase or tenecteplase) as per standard care at each site; endovascular thrombectomy was also per standard of care, using the Trevo device (Stryker Neurovascular, Fremont, CA, USA) as first-line intervention. Personnel assessing outcomes were masked to group allocation; patients and treating physicians were not. The primary efficacy endpoint was functional independence defined as modified Rankin Scale score 0-2 or return to baseline at 90 days, with a non-inferiority margin of -0·1, analysed by intention to treat (including all randomly assigned and consenting patients) and per protocol. The intention-to-treat population was included in the safety analyses. The trial is registered with ClinicalTrials.gov, NCT03494920, and is closed to new participants.Between June 2, 2018, and July 8, 2021, 295 patients were randomly assigned to direct endovascular thrombectomy (n=148) or bridging therapy (n=147). Functional independence occurred in 80 (55%) of 146 patients in the direct thrombectomy group and 89 (61%) of 147 patients in the bridging therapy group (intention-to-treat risk difference -0·051, two-sided 95% CI -0·160 to 0·059; per-protocol risk difference -0·062, two-sided 95% CI -0·173 to 0·049). Safety outcomes were similar between groups, with symptomatic intracerebral haemorrhage occurring in two (1%) of 146 patients in the direct group and one (1%) of 147 patients in the bridging group (adjusted odds ratio 1·70, 95% CI 0·22-13·04) and death in 22 (15%) of 146 patients in the direct group and 24 (16%) of 147 patients in the bridging group (adjusted odds ratio 0·92, 95% CI 0·46-1·84).We did not show non-inferiority of direct endovascular thrombectomy compared with bridging therapy. The additional information from our study should inform guidelines to recommend bridging therapy as standard treatment.Australian National Health and Medical Research Council and Stryker USA.

The optimal general anesthetic (GA) technique for stroke patients undergoing endovascular thrombectomy (ET) is unclear. We compared favorable outcomes and mortality in patients receiving propofol or volatile GA during ET and assessed associations between mean arterial pressure (MAP) and outcome.Ninety-three patients with anterior circulation stroke who received propofol or volatile GA during ET between February 2015 and February 2018 were included in this retrospective study. Ninety-day modified Rankin scores were compared and mortality was adjusted for intravenous thrombolysis and diabetes. We performed ordinal logistic regression analyses containing MAP time/exposure thresholds.There was no difference in the rate of favorable outcome (modified Rankin scores 0-2) in the volatile and propofol groups (48.8% vs. 55.8%, respectively; P=0.5). Ninety-day mortality was lower in patients receiving propofol (11.5%) than in those receiving volatile GA (29.3%) (odds ratio, 0.32; 95% confidence interval, 0.11 to 0.94; P=0.03); this mortality benefit was greater in patients that did not receive intravenous thrombolysis before ET (odds ratio for survival, 6; 95% confidence interval, 1.13 to 31.74). There was no difference in MAP between groups and a (nonsignificant) trend towards the benefit of MAP90 mm Hg but not70 mm Hg.Favorable outcome rates were similar in stroke patients receiving propofol or volatile GA during ET. Propofol was associated with lower mortality, an effect magnified in patients that did not receive intravenous thrombolysis. MAP time/exposure thresholds were associated with outcome but independent of the anesthetic agent. Our data suggest that a difference in outcome related to an anesthetic agent may exist; this hypothesis needs to be tested in a prospective study.

Background: Middle meningeal artery (MMA) embolization has recently emerged as a potential treatment for chronic subdural hematoma (cSDH). Numerous retrospective studies have suggested that it can potentially reduce the risk of hematoma recurrence following surgical evacuation. We have conducted a randomized controlled trial to investigate the effectiveness of postoperative MMA embolization in reducing recurrence rate, residual hematoma thickness as well as improving functional outcome. Methods: Patients aged 18 or above were recruited. Following evacuation through burr hole or craniotomy, patients were randomly allocated to undergo either MMA embolization or standard care (monitoring). The primary outcome was symptomatic recurrence requiring redo evacuation. Secondary outcomes include residual hematoma thickness and modified Rankin Scale (mRS) at 6 weeks and 3 months. Results: Thirty-six patients (41 cSDHs) were recruited between April 2021 and September 2022. Seventeen patients (19 cSDHs) were allocated to the embolization group and 19 patients (22 cSDHs) were in the control group. No symptomatic recurrence was observed in the treatment group while 3 control patients (15.8%) underwent repeat surgery for symptomatic recurrence, however, it was not statistically significant (P = 0.234). Furthermore, there was no significant difference in residual hematoma thickness at 6 weeks or 3 months between the two groups. All patients in the embolization group had a good functional outcome (mRS 0–1) at 3 months, which was significantly higher than the 53% observed in the control group. No complications related to MMA embolization were reported. Conclusion: Further study with larger sample size is required to evaluate the efficacy of MMA embolization.

Importance Intravenous thrombolysis with tenecteplase improves reperfusion prior to endovascular thrombectomy for ischemic stroke compared with alteplase. Objective To determine whether 0.40 mg/kg of tenecteplase safely improves reperfusion before endovascular thrombectomy vs 0.25 mg/kg of tenecteplase in patients with large vessel occlusion ischemic stroke. Design, setting, and participants Randomized clinical trial at 27 hospitals in Australia and 1 in New Zealand using open-label treatment and blinded assessment of radiological and clinical outcomes. Patients were enrolled from December 2017 to July 2019 with follow-up until October 2019. Adult patients (N = 300) with ischemic stroke due to occlusion of the intracranial internal carotid, \basilar, or middle cerebral artery were included less than 4.5 hours after symptom onset using standard intravenous thrombolysis eligibility criteria. Interventions Open-label tenecteplase at 0.40 mg/kg (maximum, 40 mg; n = 150) or 0.25 mg/kg (maximum, 25 mg; n = 150) given as a bolus before endovascular thrombectomy. Main outcomes and measures The primary outcome was reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, assessed by consensus of 2 blinded neuroradiologists. Prespecified secondary outcomes were level of disability at day 90 (modified Rankin Scale [mRS] score; range, 0-6); mRS score of 0 to 1 (freedom from disability) or no change from baseline at 90 days; mRS score of 0 to 2 (functional independence) or no change from baseline at 90 days; substantial neurological improvement at 3 days; symptomatic intracranial hemorrhage within 36 hours; and all-cause death. Results All 300 patients who were randomized (mean age, 72.7 years; 141 [47%] women) completed the trial. The number of participants with greater than 50% reperfusion of the previously occluded vascular territory was 29 of 150 (19.3%) in the 0.40 mg/kg group vs 29 of 150 (19.3%) in the 0.25 mg/kg group (unadjusted risk difference, 0.0% [95% CI, -8.9% to -8.9%]; adjusted risk ratio, 1.03 [95% CI, 0.66-1.61]; P = .89). Among the 6 secondary outcomes, there were no significant differences in any of the 4 functional outcomes between the 0.40 mg/kg and 0.25 mg/kg groups nor in all-cause deaths (26 [17%] vs 22 [15%]; unadjusted risk difference, 2.7% [95% CI, -5.6% to 11.0%]) or symptomatic intracranial hemorrhage (7 [4.7%] vs 2 [1.3%]; unadjusted risk difference, 3.3% [95% CI, -0.5% to 7.2%]). Conclusions and relevance Among patients with large vessel occlusion ischemic stroke, a dose of 0.40 mg/kg, compared with 0.25 mg/kg, of tenecteplase did not significantly improve cerebral reperfusion prior to endovascular thrombectomy. The findings suggest that the 0.40-mg/kg dose of tenecteplase does not confer an advantage over the 0.25-mg/kg dose in patients with large vessel occlusion ischemic stroke in whom endovascular thrombectomy is planned. Trial registration ClinicalTrials.gov Identifier: NCT03340493.

Background: Mechanical thrombectomy (MT) became standard care in 2015 after positive trials in patients presenting with acute ischemic stroke and large vessel occlusion (LVO) 0-6h and in 2018 for selected patients up to 24h from symptom onset. Objective: To evaluate whether patients receiving MT at our center would have comparable outcomes in patients presenting to our comprehensive stroke center (direct) vs transfer patients (drip-and-ship) Methods: This is a retrospective observational study utilising prospectively collected stroke database for patients receiving MT for LVO in anterior and posterior circulation in South Brisbane network of 7 hospitals (6 drip-and-ship centers and 1 MT-capable center), Australia which serves 1.6 million. Day 90 modified Rankin scale (mRS) was used to assess functional outcomes via outpatient follow up at direct or referral center. The association of drip and ship versus mothership treatment with day 90 mRS was tested in ordinal logistic regression adjusted for age, baseline NIHSS and IV thrombolysis. Results: Of 191 patients who underwent Mechanical Thrombectomy from 2015 to June 2018 at our center, 22 patients were excluded from analysis as either their baseline mRS was >1 (13) or follow up data was missing (9). The mean age was 64.4 years. Median (inter-quartile range, IQR) NIHSS was 16 (9-21) on admission and 7 (2-18) on day 1. Thrombolysis in Cerebral Infarction (TICI) ≥2b was achieved in 88.9%. At 90 days, 50.9% achieved excellent functional outcome (mRS 0-1), 61.4% achieved good functional outcome (mRS 0-2) and 69% achieved favorable outcome (mRS 0-3). Median mRS was 1 (IQR 0-5) in 96 patients presenting directly to the endovascular center and 1 (IQR 1-4) in 73 drip-and-ship patients (common odds ratio 1.07 (95%CI 0.62-1.83), p=0.82) Conclusion: Our 7-center network experience confirms real world reproducibility of trial results, interestingly with no difference in functional outcomes for direct vs drip-and-ship patients.

Background and hypothesis Intravenous thrombolysis with alteplase remains standard care prior to thrombectomy for eligible patients within 4.5 h of ischemic stroke onset. However, alteplase only succeeds in reperfusing large vessel arterial occlusion prior to thrombectomy in a minority of patients. We hypothesized that tenecteplase is non-inferior to alteplase in achieving reperfusion at initial angiogram, when administered within 4.5 h of ischemic stroke onset, in patients planned to undergo endovascular therapy. Study design EXTEND-IA TNK is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, blinded-endpoint non-inferiority study. Eligibility requires a diagnosis of ischemic stroke within 4.5 h of stroke onset, pre-stroke modified Rankin Scale≤3 (no upper age limit), large vessel occlusion (internal carotid, basilar, or middle cerebral artery) on multimodal computed tomography and absence of contraindications to intravenous thrombolysis. Patients are randomized to either IV alteplase (0.9 mg/kg, max 90 mg) or tenecteplase (0.25 mg/kg, max 25 mg) prior to thrombectomy. Study outcomes The primary outcome measure is reperfusion on the initial catheter angiogram, assessed as modified treatment in cerebral infarction 2 b/3 or the absence of retrievable thrombus. Secondary outcomes include modified Rankin Scale at day 90 and favorable clinical response (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0–1) at day 3. Safety outcomes are death and symptomatic intracerebral hemorrhage. Trial registration ClinicalTrials.gov NCT02388061

A healthy 51-year-old female presented with a spontaneous direct carotid-cavernous sinus fistula associated with a persistent primitive trigeminal artery. She had no history of connective tissue or cerebrovascular disorders or significant head trauma. This is a rare lesion with only 18 previously reported cases. It had similar clinical presentation and imaging appearance to a high-flow direct carotid-cavernous fistula and was uncovered after successful trans-venous coil embolisation of the fistula. It therefore needs to be considered in cases of direct carotid-cavernous fistula without history of trauma. Knowledge of types of persistent primitive trigeminal artery is also important for their critical treatment implications.

Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion.We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage.Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group.Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset. (Funded by the National Health and Medical Research Council of Australia and others; EXTEND-IA TNK ClinicalTrials.gov number, NCT02388061 .).

Introduction Severely tilted and embedded inferior vena cava (IVC) filters remain the most challenging IVC filters to remove. Heavy endothelialisation over the filter hook can prevent engagement with standard snare and cone recovery techniques. The rigid forceps technique offers a way to dissect the endothelial cap and reliably retrieve severely tilted and embedded filters. By developing this technique, failed IVC retrieval rates can be significantly reduced and the optimum safety profile offered by temporary filters can be achieved. We present our initial experience with the rigid forceps technique described by Stavropoulos et al. for removing wall-embedded IVC filters. Methods We retrospectively reviewed the medical imaging and patient records of all patients who underwent a rigid forceps filter removal over a 22-month period across two tertiary referral institutions. Results The rigid forceps technique had a success rate of 85% (11/13) for IVC filter removals. All filters in the series showed evidence of filter tilt and embedding of the filter hook into the IVC wall. Average filter tilt from the Z-axis was 19 degrees (range 8–56). Filters observed in the case study were either Bard G2X (n = 6) or Cook Celect (n = 7). Average filter dwell time was 421 days (range 47–1053). There were no major complications observed. Conclusion The rigid forceps technique can be readily emulated and is a safe and effective technique to remove severely tilted and embedded IVC filters. The development of this technique across both institutions has increased the successful filter removal rate, with perceived benefits to the safety profile of our IVC filter programme.

Background: Recent data suggest that infrapopliteal percutaneous transluminal angioplasty (PTA) is a reasonable primary therapy for critical limb ischaemia (CLI). Based on the transatlantic intersociety consensus (TASC) classification, this has been found to be true for lesions classified as A, B or C. We report our experience with infrapopliteal PTA stratified by TASC classification. Methods: A retrospective study of patients who underwent infrapopliteal PTA with or without stenting from October 2007 to July 2011 was conducted, revealing 83 limbs. The primary outcome variables were freedom from reintervention and freedom from index limb amputation. Secondary outcomes were technical success, post-operative complications and survival. TASC classification was assessed for the individual vessel(s) chosen for intervention. Results: Median age was 76 years and radiological success was 86.75%. Average follow-up was 15 months. At 1 and 2 years, freedom from re-intervention, or amputation was 65.1% and 55.6%. Limb salvage was 77.7%. Within 2 years, 2% underwent bypass and 18% repeat infrapopliteal PTA. The 30-day mortality was 5%. Overall survival was 84.5%, 71.8% and 61.6% at 1, 2 and 3 years. Eighty-twopercent were classified as TASC D lesions. Radiological success was achieved in 100% of TASC C lesions in contrast to 86.7% of TASC D lesions. There was not a statistically significant relationship between primary outcomes and TASC D classification. Discussion: Given the encouragingly high rates of radiological success and limb salvage, an attempt at PTA is indicated as an alternative to primary amputation even in patients with radiologically demonstrated severe disease.

Severely tilted and embedded inferior vena cava (IVC) filters remain the most challenging IVC filters to remove. Heavy endothelialisation over the filter hook can prevent engagement with standard snare and cone recovery techniques. The rigid forceps technique offers a way to dissect the endothelial cap and reliably retrieve severely tilted and embedded filters. By developing this technique, failed IVC retrieval rates can be significantly reduced and the optimum safety profile offered by temporary filters can be achieved. We present our initial experience with the rigid forceps technique described by Stavropoulos et al. for removing wall-embedded IVC filters.We retrospectively reviewed the medical imaging and patient records of all patients who underwent a rigid forceps filter removal over a 22-month period across two tertiary referral institutions.The rigid forceps technique had a success rate of 85% (11/13) for IVC filter removals. All filters in the series showed evidence of filter tilt and embedding of the filter hook into the IVC wall. Average filter tilt from the Z-axis was 19 degrees (range 8-56). Filters observed in the case study were either Bard G2X (n = 6) or Cook Celect (n = 7). Average filter dwell time was 421 days (range 47-1053). There were no major complications observed.The rigid forceps technique can be readily emulated and is a safe and effective technique to remove severely tilted and embedded IVC filters. The development of this technique across both institutions has increased the successful filter removal rate, with perceived benefits to the safety profile of our IVC filter programme.

Recent data suggest that infrapopliteal percutaneous transluminal angioplasty (PTA) is a reasonable primary therapy for critical limb ischaemia (CLI). Based on the transatlantic intersociety consensus (TASC) classification, this has been found to be true for lesions classified as A, B or C. We report our experience with infrapopliteal PTA stratified by TASC classification.A retrospective study of patients who underwent infrapopliteal PTA with or without stenting from October 2007 to July 2011 was conducted, revealing 83 limbs. The primary outcome variables were freedom from reintervention and freedom from index limb amputation. Secondary outcomes were technical success, post-operative complications and survival. TASC classification was assessed for the individual vessel(s) chosen for intervention.Median age was 76 years and radiological success was 86.75%. Average follow-up was 15 months. At 1 and 2 years, freedom from re-intervention, or amputation was 65.1% and 55.6%. Limb salvage was 77.7%. Within 2 years, 2% underwent bypass and 18% repeat infrapopliteal PTA. The 30-day mortality was 5%. Overall survival was 84.5%, 71.8% and 61.6% at 1, 2 and 3 years. Eighty-two per cent were classified as TASC D lesions. Radiological success was achieved in 100% of TASC C lesions in contrast to 86.7% of TASC D lesions. There was not a statistically significant relationship between primary outcomes and TASC D classification.Given the encouragingly high rates of radiological success and limb salvage, an attempt at PTA is indicated as an alternative to primary amputation even in patients with radiologically demonstrated severe disease.