Mark Dannenbaum

Endovascular therapy for acute ischemic stroke with occlusion of the middle cerebral artery M2 segment

Importance Randomized clinical trials have shown the superiority of endovascular therapy (EVT) compared with best medical management for acute ischemic strokes with large vessel occlusion (LVO) in the anterior circulation. However, of 1287 patients enrolled in 5 trials, 94 with isolated second (M2) segment occlusions were randomized and 51 of these received EVT, thereby limiting evidence for treating isolated M2 segment occlusions as reflected in American Heart Association guidelines. Objective To evaluate EVT safety and effectiveness in M2 occlusions in a cohort of patients with acute ischemic stroke. Design, Setting, and Participants This multicenter retrospective cohort study pooled patients with acute ischemic strokes and LVO isolated to M2 segments from 10 US centers. Patients with acute ischemic strokes and LVO in M2 segments presenting within 8 hours from their last known normal clinical status (LKN) from January 1, 2012, to April 30, 2015, were divided based on their treatment into EVT and medical management groups. Logistic regression was used to compare the 2 groups. Univariate and multivariate analyses evaluated associations with good outcome in the EVT group. Main Outcomes and Measures The primary outcome was the 90-day modified Rankin Scale score (range, 0-6; scores of 0-2 indicate a good outcome); the secondary outcome was symptomatic intracerebral hemorrhage. Results A total of 522 patients (256 men [49%]; 266 women [51%]; mean [SD] age, 68 [14.3] years) were identified, of whom 288 received EVT and 234 received best medical management. Patients in the medical management group were older (median [interquartile range] age, 73 [60-81] vs 68 [56-78] years) and had higher rates of intravenous tissue plasminogen activator treatment (174 [74.4%] vs 172 [59.7%]); otherwise the 2 groups were balanced. The rate of good outcomes was higher for EVT (181 [62.8%]) than for medical management (83 [35.4%]). The EVT group had 3 times the odds of a good outcome as the medical management group (odds ratio [OR], 3.1; 95% CI, 2.1-4.4; P < .001) even after adjustment for age, National Institute of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early Computed Tomographic Score (ASPECTS), intravenous tissue plasminogen activator treatment, and time from LKN to arrival in the emergency department (OR, 3.2; 95% CI, 2-5.2; P < .001). No statistical difference in symptomatic intracerebral hemorrhage was found (5.6% vs 2.1% for the EVT group vs the medical management group; P = .10). The treatment effect did not change after adjusting for center (OR, 3.3; 95% CI, 1.9-5.8; P < .001). Age, NIHSS score, ASPECTS, time from LKN to reperfusion, and successful reperfusion score of at least 2b (range, 0 [no perfusion] to 3 [full perfusion with filling of all distal branches]) were independently associated with good outcome of EVT. A linear association was found between good outcome and time from LKN to reperfusion. Conclusions and Relevance Although a randomized clinical trial is needed to confirm these findings, available data suggest that EVT is reasonable, safe, and effective for LVO of the M2 segment relative to best medical management.

Optimizing Prediction Scores for Poor Outcome After Intra-Arterial Therapy in Anterior Circulation Acute Ischemic Stroke

Background and Purpose— Intra-arterial therapy (IAT) promotes recanalization of large artery occlusions in acute ischemic stroke. Despite high recanalization rates, poor clinical outcomes are common. We attempted to optimize a score that combines clinical and imaging variables to more accurately predict poor outcome after IAT in anterior circulation occlusions. Methods— Patients with acute ischemic stroke undergoing IAT at University of Texas (UT) Houston for large artery occlusions (middle cerebral artery or internal carotid artery) were reviewed. Independent predictors of poor outcome (modified Rankin Scale, 4–6) were studied. External validation was performed on IAT-treated patients at Emory University. Results— A total of 163 patients were identified at UT Houston. Independent predictors of poor outcome (P⩽0.2) were identified as score variables using sensitivity analysis and logistic regression. Houston Intra-Arterial Therapy 2 (HIAT2) score ranges 0 to 10: age (⩽59=0, 60–79=2, ≥80 years=4), glucose (<150=0, ≥150=1), National Institute Health Stroke Scale (⩽10=0, 11–20=1, ≥21=2), the Alberta Stroke Program Early CT Score (8–10=0, ⩽7=3). Patients with HIAT2≥5 were more likely to have poor outcomes at discharge (odds ratio, 6.43; 95% confidence interval, 2.75–15.02; P<0.001). After adjusting for reperfusion (Thrombolysis in Cerebral Infarction score ≥2b) and time from symptom onset to recanalization, HIAT2≥5 remained an independent predictor of poor outcome (odds ratio, 5.88; 95% confidence interval, 1.96–17.64; P=0.02). Results from the cohort of Emory (198 patients) were consistent; patients with HIAT2 score ≥5 had 6× greater odds of poor outcome at discharge and at 90 days. HIAT2 outperformed other previously published predictive scores. Conclusions— The HIAT2 score, which combines clinical and imaging variables, performed better than all previous scores in predicting poor outcome after IAT for anterior circulation large artery occlusions.

Effect of antiplatelet therapy and platelet function testing on hemorrhagic and thrombotic complications in patients with cerebral aneurysms treated with the pipeline embolization device: a review and meta-analysis.

Purpose The pipeline embolization device (PED) necessitates dual antiplatelet therapy (APT) to decrease thrombotic complications while possibly increasing bleeding risks. The role of APT dose, duration, and response in patients with hemorrhagic and thromboembolic events warrants further analysis. Methods A PubMed and Google Scholar search from 2009 to 2014 was performed using the following search terms individually or in combination: pipeline embolization device, aneurysm(s), and flow diversion, excluding other flow diverters. Review of the bibliographies of the retrieved articles yielded 19 single and multicenter studies. A statistical meta-analysis between aspirin (ASA) dose (low dose ≤160 mg, high dose ≥300 mg), loading doses of APT agents, post-PED APT regimens, and platelet function testing (PFT) with hemorrhagic or thrombotic complications was performed. Results ASA therapy for ≤6 months post-PED was associated with increased hemorrhagic events. High dose ASA ≤6 months post-PED was associated with fewer thrombotic events compared with low dose ASA. Post-PED clopidogrel for ≤6 months demonstrated an increased incidence of symptomatic thrombotic events. Loading doses of ASA plus clopidogrel demonstrated a decreased incidence of permanent symptomatic hemorrhagic events. PFT did not show a statistically significant relationship with symptomatic hemorrhagic or thrombotic complications. Conclusions High dose ASA >6 months is associated with fewer permanent thrombotic and hemorrhagic events. Clopidogrel therapy ≤6 months is associated with higher rates of thrombotic events. Loading doses of ASA and clopidogrel were associated with a decreased incidence of hemorrhagic events. PFT did not have any significant association with symptomatic events.

A Randomized Trial of Unruptured Brain Arteriovenous Malformations Trial: An Editorial Review

A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) is the first randomized trial that attempts to answer the clinical question: what is the best management for an unruptured brain arteriovenous malformation (AVM).1 More concisely, is the natural history or is treatment the riskier management choice? Unquestionably, the investigators engaged in a difficult task. AVMs are different in each individual and so are their treatments.2 Therefore, any randomized trial of AVM management will pose many methodological problems and provoke criticisms from the outset and may not be able to provide definitive answers to many pivotal questions. ARUBA separated unruptured AVMs into a medical treatment alone group (109 patients) and an interventional group subjected to open surgery, radiosurgery, endovascular intervention, or combinations (114 patients).1 The study followed all of these patients until primary end points, such as death or symptomatic stroke, were reached. The study was terminated prematurely at 33.3 months because the incidence of primary end points was dramatically higher in the treatment group compared with the medical management group (30.7% versus 10.1%).1 The first great concern with this study is the generalization that one treatment method is equal in complexity to the other, that is, a simple either/or choice between 2 management methods. Medical management (observation) is a homogenous management delivery system with almost zero clinical variability between practitioners. Interventional therapy, however, represents several individual technologies and methods that are heterogeneous and complex.3 Surgery, endovascular intervention, and radiosurgery are not the same in any shape or form, and when combinations of therapy are included in the analysis, …

Antiplatelet therapy for the prevention of peri-coiling thromboembolism in high-risk patients with ruptured intracranial aneurysms

OBJECTIVE The most frequent procedural complication of the endovascular treatment of intracranial aneurysms is a thromboembolic event (TEE); in a subset of patients, such events will cause permanent neurological disability. In patients with unruptured aneurysms, increasing evidence supports the use of periprocedural antiplatelet therapy to prevent TEEs. The object of this study was to evaluate whether patients with ruptured aneurysms and subarachnoid hemorrhage would also benefit from periprocedural antiplatelet therapy. METHODS The authors reviewed a prospective registry of 169 patients with endovascularly treated intracranial aneurysms to delineate angiographic features associated with periprocedural TEEs. They then performed a controlled before-and-after study in 79 patients with ruptured aneurysms who were deemed to be at high risk for TEEs (for example, patients with at least 1 angiographic feature associated with TEEs) to evaluate whether selective aspirin administration would reduce the rate of periprocedural thromboembolism without increasing major hemorrhagic complications. RESULTS Six angiographic features were associated with periprocedural TEEs in the study cohort: wide aneurysm neck, coil or loop protrusion, small parent artery diameter, an incorporated branch, intraprocedural thrombus formation, and intracranial parent vessel atherosclerosis. Aspirin administration to high-risk patients significantly decreased the rate of periprocedural TEEs, from 53.8% in the control group to 10.6% in the aspirin-treated group (p = 0.001). The reduction in TEEs in the aspirin-treated group continued to be statistically significant even when adjusted for age, sex, cardiovascular risk factors (smoking, diabetes, hypertension, dyslipidemia, coronary artery disease), and factors associated with TEEs in other large studies (wide aneurysm neck, aneurysm size ≥ 10 mm), with an adjusted OR of 0.16 (95% CI 0.03-0.8). There were no major systemic hemorrhagic complications, and aspirin did not increase the risk of aneurysm rebleeding, symptomatic intracranial hemorrhage, or major external ventricular drain (EVD)-associated hemorrhage (p = 0.3), though there was an increase in asymptomatic, minor (< 1 cm) EVD-associated hemorrhage in the aspirin-treated group (p = 0.02). CONCLUSIONS The study findings suggest that for ruptured aneurysm patients with high-risk features, antiplatelet therapy can significantly reduce the rate of periprocedural TEE without increasing major systemic or intracranial hemorrhages.

USE OF FEMORAL ARTERY ULTRASOUND DURING INTRAARTERIAL CHEMOTHERAPY FOR CHILDREN UNDER 10 KG WITH RETINOBLASTOMA

Purpose: To demonstrate the safety and efficacy of intraarterial chemotherapy (IAC) in small infants (<10 kg) with retinoblastoma. Methods: Retrospective, consecutive, observational case series of patients treated with IAC. Femoral arterial access was obtained using a micropuncture kit and ultrasound guidance, which enabled direct visualization. Melphalan (1.5–5.0 mg), topotecan (0.3–2.0 mg), and/or carboplatin (30–40 mg) were used. Patients underwent adjuvant therapies including laser, cryotherapy, and intravitreal melphalan if persistent disease or recurrence was observed. Results: Fifty-nine injections were administered to 11 eyes of 6 patients. All eyes but one were classified as International Classification Groups C or D. Median patient weight at first IAC cycle was 9.2 kg (mean, 8.9 kg). Median diameter of the femoral artery at the catheterization site was 3.74 mm, measured by two independent observers. Median follow-up was 21.4 months (range 13.1–34.5 months). All eyes were salvaged. Conclusion: This study confirmed the safety and efficacy of IAC in infants under 10 kg. Ultrasound guidance enabled successful catheterization of femoral arteries as small as 2.7 mm in diameter. Patients in this study appeared to require fewer injections and lower total doses of chemotherapy compared with previously reported series of comparably advanced disease in larger infants.

Safety and Feasibility of Argatroban, Recombinant Tissue Plasminogen Activator, and Intra-Arterial Therapy in Stroke (ARTSS-IA Study)

BACKGROUND A randomized trial of concurrent recombinant tissue-type plasminogen activator (r-tPA) + thrombin-inhibition with Argatroban in stroke patients recently demonstrated safety and signal of efficacy compared to r-tPA alone, but patients having endovascular therapy (EVT) were excluded. The current study intended to study feasibility and safety of concurrent r-tPA and Argatroban in patients undergoing EVT. METHODS We conducted a single-arm, feasibility, and safety study of patients that received standard-dose r-tPA, had intracranial large vessel occlusions, and underwent EVT within 6 hours of stroke onset. During r-tPA, a 100 μg/kg Argatroban bolus, followed by 12-hour infusion, targeted an activated Partial Thromboplastin Time (aPTT) 2.25 timesbaseline. Feasibility was defined as ability to combine treatments without EVT time-metric delays, compared to cotemporaneous r-tPA + EVT treatments. Safety was incidence of symptomatic intracerebral hemorrhage (sICH), systemic hemorrhage, or EVT complications. RESULTS All preplanned 10 patients were enrolled. Arterial occlusions were middle cerebral artery (n = 8), internal carotid artery (n = 1), and posterior cerebral artery (n = 1). All received Argatroban before EVT and completed infusions. There were no delays in time-metrics compared to nonstudy patients during the same period. Nine patients achieved excellent angiographic reperfusion (Thrombolysis In Cerebral Ischemia [TICI] ≥2b); with 7 complete (TICI = 3). There were no sICH, systemic hemorrhage, or EVT complications. At 90 days, 6 (60%) patients had a modified Rankin Scale of 0-2 and none died. CONCLUSIONS In patients treated with r-tPA and EVT, concomitant Argatroban is feasible, does not delay EVT provision, produces high rates of recanalization, is probably safe, and warrants further study.

Preoperative Tumor Embolization

The resection of vascular intra- and extracranial tumors is among the greatest challenges faced by neurological and ENT surgeons. Adjunctive techniques such as stereotactic imaging and neuronavigation have greatly enhanced the safety and efficacy of these procedures. Neurointervention also has a role to play in these complex conditions. Preoperative tumor embolization may reduce blood loss and the need of complex skull base approaches to occlude large vascular pedicles.