Gary Duckwiler

Mechanical Thrombectomy for Acute Ischemic Stroke Final Results of the Multi MERCI Trial

Background and Purpose— Endovascular mechanical thrombectomy may be used during acute ischemic stroke due to large vessel intracranial occlusion. First-generation MERCI devices achieved recanalization rates of 48% and, when coupled with intraarterial thrombolytic drugs, recanalization rates of 60% have been reported. Enhancements in embolectomy device design may improve recanalization rates. Methods— Multi MERCI was an international, multicenter, prospective, single-arm trial of thrombectomy in patients with large vessel stroke treated within 8 hours of symptom onset. Patients with persistent large vessel occlusion after IV tissue plasminogen activator treatment were included. Once the newer generation (L5 Retriever) device became available, investigators were instructed to use the L5 Retriever to open vessels and could subsequently use older generation devices and/or intraarterial tissue plasminogen activator. Primary outcome was recanalization of the target vessel. Results— One hundred sixty-four patients received thrombectomy and 131 were initially treated with the L5 Retriever. Mean age±SD was 68±16 years, and baseline median (interquartile range) National Institutes of Health Stroke Scale score was 19 (15 to 23). Treatment with the L5 Retriever resulted in successful recanalization in 75 of 131 (57.3%) treatable vessels and in 91 of 131 (69.5%) after adjunctive therapy (intraarterial tissue plasminogen activator, mechanical). Overall, favorable clinical outcomes (modified Rankin Scale 0 to 2) occurred in 36% and mortality was 34%; both outcomes were significantly related to vascular recanalization. Symptomatic intracerebral hemorrhage occurred in 16 patients (9.8%); 4 (2.4%) of these were parenchymal hematoma type II. Clinically significant procedural complications occurred in 9 (5.5%) patients. Conclusions— Higher rates of recanalization were associated with a newer generation thrombectomy device compared with first-generation devices, but these differences did not achieve statistical significance. Mortality trended lower and the proportion of good clinical outcomes trended higher, consistent with better recanalization.

Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion magnetic resonance imaging.

Diffusion magnetic resonance imaging provides an early marker of acute cerebral ischemic injury. Thrombolytic reversal of diffusion abnormalities has not previously been demonstrated in humans. Serial diffusion and perfusion imaging studies were acquired in patients experiencing acute hemispheric cerebral ischemia treated with intra‐arterial thrombolytic therapy within 6 hours of symptom onset. Seven patients met inclusion criteria of prethrombolysis and postthrombolysis magnetic resonance studies, presence of large artery anterior circulation occlusion at angiography, and achievement of vessel recanalization. Mean diffusion‐weighted imaging lesion volume at baseline was 23 cm3 (95% confidence interval [95% CI], 8–38 cm3) and decreased to 10 cm3 (95% CI, 3–17 cm3) 2.5 to 9.5 hours after thrombolysis. Mean apparent diffusion coefficient lesion volume decreased from 9 cm3 (95% CI, 2–16 cm3) at baseline to 1 cm3 (95% CI, 0.4–2 cm3) early after thrombolysis. A secondary increase in diffusion volumes was seen in 3 of 6 patients at day 7. In all 4 patients in whom perfusion imaging was obtained before and after treatment, complete resolution of the perfusion deficit was shown. Diffusion magnetic resonance signatures of early tissue ischemic injury can be reversed in humans by prompt thrombolytic vessel recanalization. The ischemic penumbra includes not only the region of diffusion/perfusion mismatch, but also portions of the region of initial diffusion abnormality. Ann Neurol 2000;47:462–469.

MERCI 1 A Phase 1 Study of Mechanical Embolus Removal in Cerebral Ischemia

Background and Purpose— To report the result of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) 1 study, a phase 1 trial to evaluate the safety and efficacy of mechanical embolectomy in the cerebral vasculature. Methods— MERCI 1 enrolled 30 patients in 7 US centers. Main inclusion criteria were: National Institutes of Health Stroke Scale score (NIHSS) ≥10; treatment performed within 8 hours from symptoms onset and contra-indication to intravenous thrombolysis; no large hypodensity on computed tomography; and occlusion of a major cerebral artery on the angiogram. Safety was defined by the absence of vascular injury or symptomatic intracranial hemorrhage. Efficacy was assessed by recanalization rate and clinical outcome at 1 month. Significant recovery was defined as 30-day modified Rankin of 0 to 2 in patients with baseline NIHSS 10 to 20 and 30-day modified Rankin of 0 to 3 in patients with baseline NIHSS >20. The procedures were performed with the Merci Retrieval System, a system specially designed for intracranial embolectomy. Results— Twenty-eight patients were treated. Median NIHSS was 22. Median time from onset to completion of treatment was 6 hours and 15 minutes. Successful recanalization with mechanical embolectomy only was achieved in 12 (43%) patients, and with additional intra-arterial tissue plasminogen activator in 18 (64%) patients. There was one procedure related technical complication, with no clinical consequence. Twelve asymptomatic and no symptomatic intracranial hemorrhages occurred. At 1 month, 9 of 8 revascularized patients and 0 of 10 nonrevascularized patients had achieved significant recovery. Conclusion— This phase 1 study shows that cerebral embolectomy with the Merci Retriever was safe and that successful recanalization could benefit a significant number of patients, even when performed in an extended 8-hour time window.

Predictors of Rehemorrhage After Treatment of Ruptured Intracranial Aneurysms The Cerebral Aneurysm Rerupture After Treatment (CARAT) Study

Background and Purpose— The primary purpose of intracranial aneurysm treatment is to prevent rupture. Risk factors for rupture after aneurysm treatment have not been clearly established, and the need to completely occlude aneurysms is debated. Methods— The Cerebral Aneurysm Rerupture After Treatment (CARAT) study is an ambidirectional cohort study of all patients with ruptured intracranial aneurysms treated with coil embolization or surgical clipping at 9 high-volume centers in the United States from 1996 to 1998. All subjects were followed through 2005, and all potential reruptures were adjudicated by a panel of 3 specialists without knowledge of the initial treatment or aneurysm characteristics. Degree of aneurysm occlusion post-treatment was evaluated as a predictor of nonprocedural rerupture in univariate Kaplan–Meier analysis (log-rank test) and in a Cox proportional-hazards model after adjustment for potential confounders and censoring at time of retreatment. Results— Among 1001 patients during a mean of 4.0 years follow-up, there were 19 postprocedural reruptures; median time to rerupture was 3 days and 58% led to death. The degree of aneurysm occlusion after treatment was strongly associated with risk of rerupture (overall risk: 1.1% for complete occlusion, 2.9% for 91% to 99% occlusion, 5.9% for 70% to 90%, 17.6% for <70%; P<0.0001 in univariate and multivariable analysis). Overall risk of rerupture tended to be greater after coil embolization compared with surgical clipping (3.4% versus 1.3%; P=0.092), but the difference did not persist after adjustment (P=0.83). Conclusions— Degree of aneurysm occlusion after the initial treatment is a strong predictor of the risk of subsequent rupture in patients presenting with subarachnoid hemorrhage, which justifies attempts to completely occlude aneurysms.

Embolization of Arteriovenous Malformations with Onyx: Clinicopathological Experience in 23 Patients

OBJECTIVE To report our experience in treatment of arteriovenous malformations (AVMs) using a new liquid embolic agent, Onyx (Micro Therapeutics, Inc., Irvine, CA). METHODS Between January 1998 and May 1999, 23 patients (8 men and 15 women) were treated. The patients’ average age was 40 years, with seizure being the most common presenting symptom (39%). The average Spetzler-Martin grade on presentation was 3. The average AVM volume before embolization was 14.5 cm3. RESULTS We observed an average 63% reduction in AVM volume after 129 arterial feeders were embolized. There were four adverse events. Two patients experienced ischemia because of inadvertent occlusion of an arterial feeder. One of these patients made a full recovery, but the other patient had a permanent deficit. Two other patients experienced transient neurological deficits that resolved within 1 week of embolization. Permanent morbidity was thus 4% (1 of 23 patients). There were no deaths. Twelve patients underwent subsequent radiosurgery, and 11 patients had surgery that resulted in complete resection of their AVMs. Histopathological examinations showed mild acute inflammation in specimens resected 1 day after embolization. Chronic inflammatory changes were observed in specimens resected more than 4 days after embolization. In two patients, angionecrosis of the embolized vessels was noted. No evidence of parenchymal hemorrhage was observed in these patients, and vessel wall integrity was maintained as well. CONCLUSION Onyx is a new nonadhesive liquid embolic agent that has been used to treat 23 patients at our institution with good results. Its nonadhesive nature and ease of use make it a promising agent in the future treatment of AVMs.

Mechanical Thrombectomy of Intracranial Internal Carotid Occlusion. Pooled Results of the MERCI and Multi MERCI Part I Trials

Background and Purpose— Acute stroke from occlusion of the intracranial internal carotid artery (ICA) generally has a poor prognosis and appears to respond poorly to intravenous thrombolysis. Mechanical thrombectomy is a newly available modality for acute stroke therapy, but it is unknown whether this endovascular therapy may have a role in the specific setting of intracranial ICA occlusion. We therefore assessed the success rate of the Merci Retriever mechanical thrombectomy device in recanalization of intracranial ICA occlusions and sought to determine whether ICA recanalization with this therapy can result in better outcomes. Methods— All patients with acute stroke from intracranial ICA occlusion were identified in the MERCI and Multi MERCI Part I trials. We determined the success rate of ICA recanalization with endovascular thrombectomy and then assessed clinical outcomes according to whether vessel recanalization was successful. Results— Eighty patients with acute stroke from intracranial ICA occlusion were identified. Of these 80 patients, 53% had successful ICA recanalization with the Merci Retriever alone and 63% had ICA recanalization with use of the Merci Retriever plus adjunctive endovascular treatment. Baseline patient characteristics and procedural complications did not differ between the recanalized and nonrecanalized groups. Good clinical outcome, defined by a modified Rankin Scale of 0 to 2 at 90 days, occurred in 39% of patients with ICA recanalization (n=19 of 49) and in 3% of patients without ICA recanalization (n=1 of 30) (P<0.001; one patient was lost to follow up for 90-day modified Rankin Scale). Ninety-day mortality was 30% (n=15 of 50) in the recanalized group and 73% (n=22 of 30) in the nonrecanalized group (P<0.001). Symptomatic hemorrhage was not significantly different between the recanalized (6% [n=3 of 50]) and nonrecanalized (16.7% [n=5 of 30]) groups (P=0.14). Hemorrhage rates were also not found to be influenced by use of intravenous thrombolysis before mechanical thrombectomy. Multivariable logistic regression identified ICA recanalization (OR=28.4, 95% CI=2.6 to >99.9) and lack of history of hypertension (OR=0.15, 95% CI=0.04 to 0.57) as significant predictors of a good 90-day outcome. Failure to recanalize the ICA (OR=0.16, 95% CI=0.05 to 0.51) and age (per decade, OR=1.07, 95% CI=1.03 to 1.13) were significant predictors of mortality at 90 days. Conclusions— Mechanical thrombectomy of acute intracranial ICA occlusion using the Merci Retriever device, alone or in combination with adjunctive endovascular therapy, has a high rate of successful vessel recanalization. Subjects with successful ICA recanalization by this method have improved poststroke clinical outcome and survival compared with subjects in which the ICA is not successfully recanalized.

Impact of collateral flow on tissue fate in acute ischaemic stroke

Background: Collaterals may sustain penumbra prior to recanalisation yet the influence of baseline collateral flow on infarct growth following endovascular therapy remains unknown. Methods: Consecutive patients underwent serial diffusion and perfusion MRI before and after endovascular therapy for acute cerebral ischaemia. We assessed the relationship between MRI diffusion and perfusion lesion indices, angiographic collateral grade and infarct growth. Tmax perfusion lesion maps were generated and diffusion–perfusion mismatch regions were divided into Tmax ⩾4 s (severe delay) and Tmax ⩾2 but <4 s (mild delay). Results: Among 44 patients, collateral grade was poor in 7 (15.9%), intermediate in 20 (45.5%) and good in 17 (38.6%) patients. Although diffusion–perfusion mismatch volume was not different depending on the collateral grade, patients with good collaterals had larger areas of milder perfusion delay than those with poor collaterals (p = 0.005). Among 32 patients who underwent day 3–5 post-treatment MRIs, the degree of pretreatment collateral circulation (r = −0.476, p = 0.006) and volume of diffusion–perfusion mismatch (r = 0.371, p = 0.037) were correlated with infarct growth. Greatest infarct growth occurred in patients with both non-recanalisation and poor collaterals. Multiple regression analysis revealed that pretreatment collateral grade was independently associated with infarct growth. Conclusion: Our data suggest that angiographic collateral grade and penumbral volume interactively shape tissue fate in patients undergoing endovascular recanalisation therapy. These angiographic and MRI parameters provide complementary information about residual blood flow that may help guide treatment decision making in acute cerebral ischaemia.

Analysis of Thrombi Retrieved From Cerebral Arteries of Patients With Acute Ischemic Stroke

Background and Purpose— Information regarding the histological structure of thromboemboli that cause acute stroke provides insight into pathogenesis and clinical management. Methods— This report describes the histological analysis of thromboemboli retrieved by endovascular mechanical extraction from the middle cerebral artery (MCA) and intracranial carotid artery (ICA) of 25 patients with acute ischemic stroke. Results— The large majority (75%) of thromboemboli shared architectural features of random fibrin:platelet deposits interspersed with linear collections of nucleated cells (monocytes and neutrophils) and confined erythrocyte-rich regions. This histology was prevalent with both cardioembolic and atherosclerotic sources of embolism. “Red” clots composed uniquely of erythrocytes were uncommon and observed only with incomplete extractions, and cholesterol crystals were notably absent. The histology of thromboemboli that could not be retrieved from 29 concurrent patients may be different. No thrombus >3 mm wide caused stroke limited to the MCA, and no thrombus >5 mm wide was removed from the ICA. A mycotic embolus was successfully removed in 1 case, and a small atheroma and attached intima were removed without clinical consequence from another. Conclusions— Thromboemboli retrieved from the MCA or intracranial ICA of patients with acute ischemic stroke have similar histological components, whether derived from cardiac or arterial sources. Embolus size determines ultimate destination, those >5 mm wide likely bypassing the cerebral vessels entirely. The fibrin:platelet pattern that dominates thromboembolic structure provides a foundation for both antiplatelet and anticoagulant treatment strategies in stroke prevention.

CT and MRI Early Vessel Signs Reflect Clot Composition in Acute Stroke

Background and Purpose— The purpose of this study was to provide the first correlative study of the hyperdense middle cerebral artery sign (HMCAS) and gradient-echo MRI blooming artifact (BA) with pathology of retrieved thrombi in acute ischemic stroke. Methods— Noncontrast CT and gradient-echo MRI studies before mechanical thrombectomy in 50 consecutive cases of acute middle cerebral artery ischemic stroke were reviewed blinded to clinical and pathology data. Occlusions retrieved by thrombectomy underwent histopathologic analysis, including automated quantitative and qualitative rating of proportion composed of red blood cells (RBCs), white blood cells, and fibrin on microscopy of sectioned thrombi. Results— Among 50 patients, mean age was 66 years and 48% were female. Mean (SD) proportion was 61% (±21) fibrin, 34% (±21) RBCs, and 4% (±2) white blood cells. Of retrieved clots, 22 (44%) were fibrin-dominant, 13 (26%) RBC-dominant, and 15 (30%) mixed. HMCAS was identified in 10 of 20 middle cerebral artery stroke cases with CT with mean Hounsfield Unit density of 61 (±8 SD). BA occurred in 17 of 32 with gradient-echo MRI. HMCAS was more commonly seen with RBC-dominant and mixed than fibrin-dominant clots (100% versus 67% versus 20%, P=0.016). Mean percent RBC composition was higher in clots associated with HMCAS (47% versus 22%, P=0.016). BA was more common in RBC-dominant and mixed clots compared with fibrin-dominant clots (100% versus 63% versus 25%, P=0.002). Mean percent RBC was greater with BA (42% versus 23%, P=0.011). Conclusions— CT HMCAS and gradient-echo MRI BA reflect pathology of occlusive thrombus. RBC content determines appearance of HMCAS and BA, whereas absence of HMCAS or BA may indicate fibrin-predominant occlusive thrombi.

Predictors of Good Clinical Outcomes, Mortality, and Successful Revascularization in Patients With Acute Ischemic Stroke Undergoing Thrombectomy: Pooled Analysis of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI Trials

Background and Purpose— The Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials evaluated the safety and efficacy of thrombectomy in the treatment of intracranial arterial occlusions within 8 hours of symptom onset. We sought to determine the predictors of clinical and angiographic outcomes in these patients. Methods— The trial cohorts were combined in a data set of 305 patients. Twenty-eight baseline variables were included in univariate and multivariate analyses to define the independent predictors of good outcomes (modified Rankin Scale score ≤2), mortality, and successful revascularization (Thrombolysis In Myocardial Ischemia 2 to 3 flow). Results— In the univariate analysis, final revascularization, baseline National Institutes of Health Stroke Scale, age, and systolic blood pressure were associated with both good outcomes and mortality at 90 days (P<0.0018 for all). In the multivariate analysis, final revascularization (OR, 20.4; 95% CI, 7.7 to 53.9; P<0.0001), baseline National Institutes of Health Stroke Scale (OR, 0.86; 95% CI, 0.81 to 0.92; P<0.0001), and age (OR, 0.96; 95% CI, 0.95 to 0.98; P=0.0004) were independent predictors of good outcome. Final revascularization (OR, 0.28; 95% CI, 0.16 to 0.50; P<0.0001), baseline National Institutes of Health Stroke Scale score (odds ratio, 1.09; 95% CI, 1.04 to 1.14; P=0.0001), age (OR, 1.05; 95% CI, 1.03 to 1.07; P<0.0001), and internal carotid artery occlusion (OR, 2.17; 95% CI, 1.22 to 3.86; P=0.0084) were the strongest predictors of mortality. Systolic blood pressure (<150 versus ≥150 mm Hg; OR, 0.42; 95% CI, 0.26 to 0.70; P=0.0007) and M2 occlusion (OR, 3.86; 95% CI, 1.28 to 11.67; P=0.0168) were independent predictors of revascularization. Conclusion— Final recanalization status represents the strongest predictor of clinical outcomes in patients undergoing thrombectomy. The ability to remove the clot is negatively influenced by systolic blood pressure on presentation perhaps because of the hydraulic forces imposed by higher blood pressures. Although internal carotid artery occlusions are associated with increased mortality, they do not appear to influence the chances of good outcomes. This finding supports the inclusion of internal carotid artery occlusions in future efficacy trials.