Endovascular Recanalization Therapy Research Articles

Acute endovascular recanalization therapy in wake-up stroke

Background and Purpose Up to 15–25% of patients with ischemic stroke wake up with their deficits. Because of the uncertainty about the time of onset, these patients are generally not offered thrombolytic therapy. Some of these wake-up stroke patients may be eligible for acute endovascular stroke therapy based on hyperacute CT or MR imaging independent of the time window. Report We report two patients with acute ischemic stroke whose symptoms were present upon awakening and who were successfully treated with endovascular interventions. Results The first patient was discharged with complete neurological recovery on second day after endovascular intervention. The second patient went home on fifth day with a mild left facial paresis and left arm drift. Both these patients did not have any neurological deficit on 18-month follow up. Conclusions Some patients who present with stroke on awakening may be candidates for thrombolytic therapy or recanalization techniques irrespective of mode of therapy (intravenous, intravenous + intra-arterial or intra-arterial tPA alone). Further randomized, controlled studies are warranted to safely identify those candidates who would benefit from thrombolysis and endovascular interventions in ischemic wake-up strokes.

Impact of Reperfusion after 3 Hours of Symptom Onset on Tissue Fate in Acute Cerebral Ischemia

Reperfusion of penumbral tissue is a promising strategy for treatment of acute cerebral ischemia more than 3 hours from symptom onset. However, there has been only sparse direct evidence that reperfusion after 3 hours prevents infarct growth. We analyzed clinical and serial magnetic resonance imaging (MRI) data on patients who received endovascular recanalization therapy 3-12 hours after last known well time. Multimodal MRIs were acquired pretreatment, early (1-20 hours), and late (2-7 days) after treatment. Degree of recanalization was assessed on end of procedure catheter angiogram, degree of reperfusion on early posttreatment perfusion MRI, and infarct growth by analysis of diffusion lesion volumes on pretreatment and late MRIs. Twenty-seven (12 men, 15 women) underwent endovascular recanalization procedures at 6.0 +/- 2.1 hours (range, 3.0-11.5 hours) after last known well time. Immediate posttreatment perfusion lesion (Tmax > or =4 seconds) volume correlated strongly with infarct growth (r= .951, P < .001), exceeding the correlations of vessel recanalization score (r=-.198, P= .446) and pretreatment diffusion-perfusion mismatch volume (r= .518, P= .033). Without reperfusion, enlargement of DWI lesion volume was observed in all patients, and extent of enlargement depended on volume of immediate posttreatment perfusion defects. Our data indicate that posttreatment reperfusion is the major determinant of threatened tissue outcome, and suggest reperfusion even after 3 hours of symptom onset can alter tissue fate over a wide range of mismatch volumes.

Impact of Hyperlipidemia and Statins on Ischemic Stroke Outcomes after Intra-Arterial Fibrinolysis and Percutaneous Mechanical Embolectomy

Background: Endovascular recanalization therapies are an increasingly employed treatment strategy in acute cerebral ischemia. The determinants of the final clinical outcome after endovascular treatment have been understudied. We investigated the effects of hyperlipidemia and statins on acute ischemic stroke outcomes after endovascular procedures. Methods: An inquiry of a prospectively maintained stroke registry was conducted. Endovascular procedures were performed using recombinant tissue plasminogen activator, prourokinase or the Merci device within 12 hours after symptom onset. The analyzed outcomes were revascularization, hemorrhage and excellent functional outcome (Rankin score of 0–1 at 3 months). The analyses included χ² and Wilcoxon rank sum, logistic regression (for multivariate analyses with binary outcomes) and linear regression (for continuous outcomes). Significance was set at p < 0.05. Results: We included 142 patients, 80% treated with intra-arterial fibrinolysis, 22% with percutaneous mechanical embolectomy and 27% treated with intravenous fibrinolysis prior to endovascular intervention. Age (OR = 0.956, 95% CI = 0.927–0.986, p = 0.0041), National Institutes of Health Stroke Scale (NIHSS) score on admission (OR = 0.881, 95% CI = 0.812–0.957, p = 0.0025) and history of hyperlipidemia (OR = 0.284, 95% CI = 0.08–0.99, p = 0.0478) were negatively associated with excellent functional outcome at 3 months. Every 50 mg/dl increment in the total cholesterol level resulted in 64% decrease in the odds of excellent functional outcome (OR = 0.36, 95% CI = 0.447–0.882, p = 0.0253). History of hyperlipidemia decreased the likelihood of neurological improvement (p = 0.0462) and was associated with a higher NIHSS score at 7 days or discharge. Statin use was related to an average 6.5-unit NIHSS decrease at discharge (p = 0.0168). Statins were not associated with increased frequency of recanalization or symptomatic intracerebral hemorrhage. Conclusions: History of hyperlipidemia may have a negative impact on the outcomes of acute ischemic stroke treated with intra-arterial fibrinolysis or percutaneous mechanical embolectomy. Statin use before and after these procedures may be related to better neurological outcomes. Larger prospective studies are needed to endorse these findings.

Major Neurologic Improvement following Endovascular Recanalization Therapy for Acute Ischemic Stroke

Background: We aimed to identify the rate of major neurologic improvement (MNI) at 24 h following endovascular recanalization therapy (ERT) for acute ischemic stroke and its association with short-term outcome. Methods: We retrospectively reviewed consecutive acute ischemic stroke patients presenting to our institution over 4 years and undergoing ERT. Angiograms were independently reviewed. Data on demographics, medical history, initial NIHSS score, 24-hour NIHSS score, site of acute vascular lesion, pre- and posttreatment Thrombolysis in Myocardial Infarction scores, symptomatic intracerebral hemorrhage (within 36 h of intervention that was associated with a 4-point decline in NIHSS score) and discharge disposition were collected. We used logistic regression analysis to identify predictors of MNI (defined as ≥8-point improvement in NIHSS or a score of 0–1 at 24 h) and favorable discharge status (defined as home or acute rehabilitation). Results: Sixty-eight patients were included (median age = 71 years, 60% women, median NIHSS score = 19.5, anterior circulation = 75%). The modes of ERT were pharmacologic only (28%), mechanical only (35%) and multimodal therapy (37%). Thrombolysis in Myocardial Infarction 2 or 3 recanalization was achieved in 64.7% (mechanical only 46%, pharmacologic only 63% and multimodal 84%). The outcomes were: symptomatic intracerebral hemorrhage (11.8%), MNI (26.5%) and favorable discharge (41.2%). Age (OR = 0.93, p = 0.003) and cardioembolic stroke subtype (OR = 6.0, p = 0.018) were independent predictors of MNI. MNI was a strong predictor of favorable discharge status (OR = 46.4, p < 0.001). Conclusions: Despite initial stroke severity, MNI occurred in over one fourth of the patients and independently and strongly predicted favorable discharge outcome.

Intra-Arterial Fibrinolysis for Acute Ischemic Stroke

See related article, pages 2633–2639. For nearly a decade, intra-arterial fibrinolytic therapy for acute ischemic stroke has stood poised on the threshold of a definitive evidential basis and widespread acceptance. The positive result of the phase 3 PROACT II trial in 1999 appeared to validate the pathophysiologically eminently reasonable strategy of endovascular recanalization in acute ischemic stroke.1 Endovascular therapy delivers lytic agent at high concentration directly to the clot, increasing lysis rates compared with intravenous therapy, while minimizing systemic exposure and extracerebral bleeding complications.2 Leading stroke centers adopted endovascular recanalization therapies as a common off-label treatment option for patients beyond the 3-hour window.3 However, proponents of evidence-based medicine noted that a single, small phase 3 clinical trial was insufficient to provide definitive proof of efficacy. The US Food and Drug Administration and international regulatory agencies did not approve a stroke label for pro-urokinase. The expense of a confirmatory phase 3 trial of pro-urokinase proved daunting to pharma and none was undertaken. In US national practice guidelines, intra-arterial fibrinolysis occupied a gray zone, receiving a Level B recommendation, indicating the incomplete foundation of a single dose-ranging and single positive phase 3 trial.4 The limitations of this evidential base have prevented regional emergency medical systems from organizing delivery of patients directly to endovascular hospitals. The results of the MELT trial, reported in this issue of Stroke , are therefore very welcome, providing additional information regarding intra-arterial fibrinolytic therapy that complements and supports previous studies. …

Endovascular Recanalization Therapy in Acute Ischemic Stroke

To assess the outcome in acute ischemic stroke patients not eligible for systemic thrombolysis (outside the 3-hour time window, after surgery, or on anticoagulant) undergoing endovascular recanalization therapy (ERT) at the Columbia University Medical Center (CUMC) and to determine US nationwide usage and outcome of ERT in acute ischemic stroke. Patients treated at CUMC from 2001 to 2004 and the Nationwide Inpatient Sample (NIS) comprising 20% of all admissions in the United States from 1999 to 2002 were analyzed retrospectively. Thirty-one patients underwent ERT. Mean age was 68+/-14 years, 68% were female, and 45% nonwhite (occlusion sites: internal carotid artery 29%; middle cerebral artery 39%; posterior circulation 32%). Pharmacological or mechanical ERT was initiated beyond 3 hours after symptom onset (median time 4.4 hours) in 61%, 29% had surgery, and 39% were on anticoagulant medication. At discharge, 32% had modified Rankin Scale scores of 0 to 2 (52% discharged home or to rehabilitation facilities); overall mortality was 29%, of which 19% were fatal intracerebral hemorrhages. From the NIS cohort, 477 patients (0.17% of all strokes and 14% of all thrombolysis cases) underwent ERT. Fifteen percent died, and approximately 50% were discharged home or to rehabilitation facilities. Intracerebral hemorrhage occurred in 6%. Fewer good outcomes of the CUMC cohort may be explained by more unfavorable premorbid patient characteristics compared with the NIS cohort. Despite significant variability in patient characteristics and treatment methods among 2 sources of data analyzed, ERT in stroke patients not eligible for intravenous thrombolysis appears to be a relatively safe and effective treatment alternative that is being used increasingly nationwide.

Approval of the MERCI Clot Retriever

Section Editors: Marc Fisher MD Antoni Davalos MD The Food and Drug Administration (FDA) evaluates applications for new human drugs, biologics, and complex medical devices. Companies must obtain FDA approval to legally market these products. In August, the FDA gave Concentric Medical clearance to market its Merci Retriever system to “remove blood clots from the brain in patients experiencing an ischemic stroke.” Given that the FDA is charged with “protecting the public health by assuring the safety, efficacy, and security of… biological products and medical devices…, ” “advancing public health by helping to speed innovations that make medicines … more effective, safer, and more affordable,” and “helping the public get the accurate, science-based information they need to use medicines … to improve their health,”1 the FDA’s decision to approve the Merci Retriever system is of concern. The pathways to approval are reviewed by Felten et al in the accompanying article and are outlined in Figure 1. Figure 1. Potential pathways for device approval. The decision to approve the Merci Retriever was based on data from the MERCI (Mechanical Embolus Removal in Cerebral Ischemia) Trial; the approval was granted through the 510(k) process. The Merci Retriever system includes a flexible nickel titanium (nitinol) wire that obtains a helical shape once it is passed through the tip of the guidance catheter. In practice, the catheter/wire is passed distal to the thrombus, the catheter is removed, and the helical configuration assumed by the wire; the clot is then trapped in the helix and withdrawn from the vasculature (Figure 2). The 510(k) clearance means that the Merci Retriever was felt to be substantially equivalent to a predicate device. In this case, the predicate device was the Concentric Retriever, which itself received 510(k) clearance by the FDA in May 2001 for “use in …