Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy: a systematic review and meta-analysis of observational data.

BACKGROUND: Achieving the best possible reperfusion is a key determinant of clinical outcome after mechanical thrombectomy (MT). However, data on the safety and efficacy of intra-arterial (IA) fibrinolytics as an adjunct to MT with the intention to improve reperfusion are sparse. METHODS: We performed a PROSPERO-registered (CRD42020149124) systematic review and meta-analysis accessing MEDLINE, PubMed, and Embase from January 1, 2000 to January 1, 2020. A random-effect estimate (Mantel-Haenszel) was computed and summary OR with 95% CI were used as a measure of added IA fibrinolytics versus control on the risk of symptomatic intracranial hemorrhage (sICH) and secondary endpoints (modified Rankin Scale ≤2, mortality at 90 days). RESULTS: The search identified six observational cohort studies and three observational datasets of MT randomized-controlled trial data reporting on IA fibrinolytics with MT as compared with MT alone, including 2797 patients (405 with additional IA fibrinolytics (100 urokinase (uPA), 305 tissue plasminogen activator (tPA)) and 2392 patients without IA fibrinolytics). Of 405 MT patients treated with additional IA fibrinolytics, 209 (51.6%) received prior intravenous tPA. We did not observe an increased risk of sICH after administration of IA fibrinolytics as adjunct to MT (OR 1.06, 95% CI 0.64 to 1.76), nor excess mortality (0.81, 95% CI 0.60 to 1.08). Although the mode of reporting was heterogeneous, some studies observed improved reperfusion after IA fibrinolytics. CONCLUSION: The quality of evidence regarding peri-interventional administration of IA fibrinolytics in MT is low and limited to observational data. In highly selected patients, no increase in sICH was observed, but there is large uncertainty.

Impact of EMS bypass to endovascular capable hospitals: geospatial modeling analysis of the US STRATIS registry.

BACKGROUND: Routing patients directly to endovascular capable centers (ECCs) would decrease time to mechanical thrombectomy (MT), but may delay intravenous thrombolysis (IVT). OBJECTIVE: To study the clinical outcomes of patients with a stroke transferred directly to ECCs compared with those transferred to ECCs from non-endovascular capable centers (nECCs). METHODS: Data from the STRATIS registry were analyzed to evaluate process and clinical outcomes under five routing policies: (1) transport to nearest nECC; (2) transport to STRATIS ECC over any distance or (3) within 20 miles; (4) transport to ideal ECC (iECC), over any distance or (5) within 20 miles. RESULTS: Among 236 patients, 117 (49.6%) were transferred by ground, of whom 62 (53%) were transferred within 20 miles. Median MT start time was accelerated in all direct transport models. IVT start was prolonged with direct transport across all distances, but accelerated with direct transport to iECC ≤20 miles. With bypass limited to ≤20 miles, the median modeled EMS arrival to IVT interval decreased for both iECCs and ECCs (by 12 min and 6 min, respectively), and median EMS arrival to puncture time decreased by up to 94 min. In this cohort, no patient would have become ineligible for IVT. Bypass to iECC modeling under 20 miles showed a significant reduction in the level of disability at 3 months, with freedom from disability (modified Rankin Scale score 0-1) at 3 months increased by 12%. CONCLUSIONS: Direct routing of patients with a large vessel occlusion to ECCs, especially when within 20 miles, may lead to better clinical outcomes by accelerating the start of MT without any delay of IVT. CLINICAL TRIAL REGISTRATION NUMBER: http://www.clinicaltrials.gov. Unique identifier: NCT02239640.

Real-world stent retriever thrombectomy for acute ischemic stroke beyond 6 hours of onset: analysis of the NASA and TRACK registries.

BACKGROUND: The DEFUSE 3 and DAWN trials have shown the benefit of thrombectomy beyond 6 hours of stroke symptom onset in carefully selected patients. OBJECTIVE: To evaluate the real-world outcomes of stent retriever thrombectomy beyond 6 hours of stroke onset using combined individual patient data from the North American Solitaire Stent Retriever Acute Stroke (NASA) and Trevo Stent-Retriever Acute Stroke (TRACK) registries. METHODS: Pooled analysis of individual patient data of all cases of anterior circulation acute ischemic stroke (AIS) from NASA and TRACK was performed to compare outcomes of patients presenting within the first hours 6 or beyond 6 hours of stroke symptom onset. RESULTS: Of 830 patients with anterior circulation AIS from the NASA and TRACK registries, 32.7% (271 patients) underwent thrombectomy beyond the first 6 hours of symptom onset. The rates of good clinical outcome (modified Rankin scale score of 0-2 at 90 days), mortality, and symptomatic intracranial hemorrhage were similar: 48.1%, 20.6%, and 8.0% within 0-6 hours, 46.2%, 21.6%, and 10.9% within 6-16 hours, and 38.9%, 33.3%, and 5% within 16-24 hours (p=0.8, 0.6, and 0.5, respectively). The rates of successful recanalization (Thrombolysis in Cerebral Infarction 2b/3) were 79.4% in patients with stroke within 0-6 hours, 72.6% within 6-16 hours, and 85.0% within 16-24 hours (p=0.04). CONCLUSIONS: Real-world experience with patients with anterior circulation AIS treated with the Solitaire and Trevo thrombectomy devices beyond the first 6 hours of symptom onset proved to be equally safe and effective as for patients with symptom onset within the first 6 hours.

North American Solitaire Stent Retriever Acute Stroke registry: post-marketing revascularization and clinical outcome results.

BACKGROUND: Limited post-marketing data exist on the use of the Solitaire FR device in clinical practice. The North American Solitaire Stent Retriever Acute Stroke (NASA) registry aimed to assess the real world performance of the Solitaire FR device in contrast with the results from the SWIFT (Solitaire with the Intention for Thrombectomy) and TREVO 2 (Trevo versus Merci retrievers for thrombectomy revascularization of large vessel occlusions in acute ischemic stroke) trials. METHODS: The investigator initiated NASA registry recruited North American sites to submit retrospective angiographic and clinical outcome data on consecutive acute ischemic stroke (AIS) patients treated with the Solitaire FR between March 2012 and February 2013. The primary outcome was a Thrombolysis in Myocardial Ischemia (TIMI) score of ≥2 or a Treatment in Cerebral Infarction (TICI) score of ≥2a. Secondary outcomes were 90 day modified Rankin Scale (mRS) score, mortality, and symptomatic intracranial hemorrhage. RESULTS: 354 patients underwent treatment for AIS using the Solitaire FR device in 24 centers. Mean time from onset to groin puncture was 363.4±239 min, mean fluoroscopy time was 32.9±25.7 min, and mean procedure time was 100.9±57.8 min. Recanalization outcome: TIMI ≥2 rate of 83.3% (315/354) and TICI ≥2a rate of 87.5% (310/354) compared with the operator reported TIMI ≥2 rate of 83% in SWIFT and TICI ≥2a rate of 85% in TREVO 2. Clinical outcome: 42% (132/315) of NASA patients demonstrated a 90 day mRS ≤2 compared with 37% (SWIFT) and 40% (TREVO 2). 90 day mortality was 30.2% (95/315) versus 17.2% (SWIFT) and 29% (TREVO 2). CONCLUSIONS: The NASA registry demonstrated that the Solitaire FR device performance in clinical practice is comparable with the SWIFT and TREVO 2 trial results.

Complete reperfusion mitigates influence of treatment time on outcomes after acute stroke.

BACKGROUND: Time to reperfusion following endovascular treatment (ET) predicts outcomes after acute ischemic stroke (AIS). OBJECTIVE: To assess the time-outcome relationship within reperfusion grades in the North American Solitaire Acute Stroke registry. METHODS: We identified patients given ET for anterior circulation ischemic stroke within 8 h from onset and in whom reperfusion was achieved. Together with clinical and outcome data, site-adjudicated modified Thrombolysis in Cerebral Ischemia (TICI) was recorded. We assessed the impact of time to reperfusion (onset to procedure completion time) on good outcome (modified Rankin Scale 0-2 at 3 months) in patients who achieved TICI 2 or higher reperfusion in multivariable models. We further assessed this relationship within strata of reperfusion grades. A p<0.05 was considered significant. RESULTS: Independent predictors of good outcome at 3 months among those achieving TICI ≥2a reperfusion (n=188) were initial National Institutes of Health Stroke Scale score (adjusted OR=0.90, 95% CI 0.85 to 0.95), symptomatic hemorrhage (adj. OR=0.16, 95% CI 0.05 to 0.60), TICI grade (TICI 3: adj. OR=11.52, 95% CI 3.34 to 39.77; TICI 2b: adj. OR=5.14, 95% CI 1.61 to 16.39), and time to reperfusion per 30 min interval (adj. OR=0.91, 95% CI 0.82 to 0.99). There was an interaction between final TICI grade and 30 min time to reperfusion intervals (p=0.001) such that the effect of time was strongest in TICI 2a patients. CONCLUSIONS: Time to reperfusion was a strong predictor of outcome following ET for AIS. However, the effect varied by TICI grade such that its greatest effect was in those achieving TICI 2a reperfusion.

Predictors of poor outcome despite recanalization: a multiple regression analysis of the NASA registry.

BACKGROUND: Mechanical thrombectomy with stent-retrievers results in higher recanalization rates compared with previous devices. Despite successful recanalization rates (Thrombolysis in Cerebral Infarction (TICI) score ≥2b) of 70-83%, good outcomes by 90-day modified Rankin Scale (mRS) score ≤2 are achieved in only 40-55% of patients. We evaluated predictors of poor outcomes (mRS >2) despite successful recanalization (TICI ≥2b) in the North American Solitaire Stent Retriever Acute Stroke (NASA) registry. METHODS: Logistic regression was used to evaluate baseline characteristics and recanalization outcomes for association with 90-day mRS score of 0-2 (good outcome) vs 3-6 (poor outcome). Univariate tests were carried out for all factors. A multivariable model was developed based on backwards selection from the factors with at least marginal significance (p≤0.10) on univariate analysis with the retention criterion set at p≤0.05. The model was refit to minimize the number of cases excluded because of missing covariate values; the c-statistic was a measure of predictive power. RESULTS: Of 354 patients, 256 (72.3%) were recanalized successfully. Based on 234 recanalized patients evaluated for 90-day mRS score, 116 (49.6%) had poor outcomes. Univariate analysis identified an increased risk of poor outcome for age ≥80 years, occlusion site of internal carotid artery (ICA)/basilar artery, National Institute of Health Stroke Scale (NIHSS) score ≥18, history of diabetes mellitus, TICI 2b, use of rescue therapy, not using a balloon-guided catheter or intravenous tissue plasminogen activator (IV t-PA), and >30 min to recanalization (p≤0.05). In multivariable analysis, age ≥80 years, occlusion site ICA/basilar, initial NIHSS score ≥18, diabetes, absence of IV t-PA, ≥3 passes, and use of rescue therapy were significant independent predictors of poor 90-day outcome in a model with good predictive power (c-index=0.80). CONCLUSIONS: Age, occlusion site, high NIHSS, diabetes, no IV t-PA, ≥3 passes, and use of rescue therapy are associated with poor 90-day outcome despite successful recanalization.

North American Solitaire Stent Retriever Acute Stroke registry: post-marketing revascularization and clinical outcome results.

BACKGROUND: Limited post-marketing data exist on the use of the Solitaire FR device in clinical practice. The North American Solitaire Stent Retriever Acute Stroke (NASA) registry aimed to assess the real world performance of the Solitaire FR device in contrast with the results from the SWIFT (Solitaire with the Intention for Thrombectomy) and TREVO 2 (Trevo versus Merci retrievers for thrombectomy revascularization of large vessel occlusions in acute ischemic stroke) trials. METHODS: The investigator initiated NASA registry recruited North American sites to submit retrospective angiographic and clinical outcome data on consecutive acute ischemic stroke (AIS) patients treated with the Solitaire FR between March 2012 and February 2013. The primary outcome was a Thrombolysis in Myocardial Ischemia (TIMI) score of ≥2 or a Treatment in Cerebral Infarction (TICI) score of ≥2a. Secondary outcomes were 90 day modified Rankin Scale (mRS) score, mortality, and symptomatic intracranial hemorrhage. RESULTS: 354 patients underwent treatment for AIS using the Solitaire FR device in 24 centers. Mean time from onset to groin puncture was 363.4±239 min, mean fluoroscopy time was 32.9±25.7 min, and mean procedure time was 100.9±57.8 min. Recanalization outcome: TIMI ≥2 rate of 83.3% (315/354) and TICI ≥2a rate of 87.5% (310/354) compared with the operator reported TIMI ≥2 rate of 83% in SWIFT and TICI ≥2a rate of 85% in TREVO 2. CLINICAL OUTCOME: 42% (132/315) of NASA patients demonstrated a 90 day mRS ≤2 compared with 37% (SWIFT) and 40% (TREVO 2). 90 day mortality was 30.2% (95/315) versus 17.2% (SWIFT) and 29% (TREVO 2). CONCLUSIONS: The NASA registry demonstrated that the Solitaire FR device performance in clinical practice is comparable with the SWIFT and TREVO 2 trial results.

Extracranial carotid artery pseudoaneurysm presenting with embolic stroke in a pediatric patient. Case report.

Extracranial carotid artery (CA) aneurysms are rare in the pediatric population and are usually the result of connective tissue disorders, traumatic dissection, or infection. The authors present the case of a large calcified internal carotid artery pseudoaneurysm of obscure origins presenting with embolic stroke in a child. Aneurysm excision and CA reconstruction would have been extremely difficult due to the distal location of the lesion, and CA ligation was contraindicated due to a failed balloon test occlusion. Therefore, after anticoagulation therapy, the patient was treated endovascularly with a covered stent and complete exclusion of the aneurysm from the circulation. The patient recovered all neurological function and has remained in excellent condition. A follow-up angiogram performed at 6 months showed no recurrence or stenosis.

Endovascular treatment of ruptured aneurysms and vasospasm.

Despite various criticisms, the International Subarachnoid Aneurysm Trial (ISAT) has provided Class I evidence that endovascular therapy (EVT) results in superior 1-year outcomes, compared with surgical repair of ruptured aneurysms equally amenable to both types of treatment. Although the lower occlusion rates and higher rates of recanalization in aneurysms treated with EVT necessitate serial imaging follow-up, these findings do not seem to translate into unacceptably high rates of rebleeding or retreatment morbidity that outweigh the upfront advantage over surgical clipping. EVT also compares favorably to surgery in the treatment of unruptured aneurysms. A randomized, controlled study similar to ISAT is needed for comparing EVT to surgery. EVT appears to have more limitations of durability in large and giant aneurysms, which warrants further research into stent or liquid embolic-assisted treatment because surgical treatment morbidity is also high. Vasospasm is a frequent and potentially devastating complication of aneurysmal subarachnoid hemorrhage. Angioplasty and intra-arterial drug therapy are effective treatments, with an acceptable morbidity and mortality. Angioplasty is more effective and durable and should be considered early in patients with signs of ischemia refractory to maximal medical therapy.

Risk of extubation failure in patients with myasthenic crisis.

INTRODUCTION: Weaning patients with myasthenic crisis (MC) from mechanical ventilation is often difficult, and the ideal time for extubation is often uncertain. However, little is known about the risk of extubation failure and the factors that may affect its occurrence. The goals of this study were to assess the risk of extubation failure in patients with MC and to determine which clinical variables may predict unsuccessful extubation. MATERIALS AND METHODS: Retrospective review of consecutive patients admitted for MC. Weaning method was categorized as T-piece or continuous positive airway pressure (i.e., T-piece trials not performed). Extubation failure was defined as need for reintubation or tracheostomy due to persistent neuromuscular insufficiency. Functional outcome was assessed using the modified Rankin score. RESULTS: We identified 26 episodes of MC in 20 patients. Median age was 42.1 years (range 14-83 years). Most patients were treated with immunomodulatory therapy (73%). There were seven episodes of extubation failure (prevalence rate 27%). Median time to reintubation was 36 hours. Older age (p = 0.05), atelectasis (p < 0.01), and pneumonia (p =0.02) were significantly associated with extubation failure. Patients with failed extubation had considerably prolonged intensive care unit stays (median 28 versus 7 days; p < 0.01) and hospital stays (median 40 versus 12 days; p < 0.01). CONCLUSION: Extubation failure may often complicate MC. Older age and development of pulmonary complications during mechanical ventilation increase the risk of extubation failure.