Robert W Tarr

Response to Intra-Arterial and Combined Intravenous and Intra-Arterial Thrombolytic Therapy in Patients With Distal Internal Carotid Artery Occlusion

Background and Purpose— The objective of this study was to determine the clinical features, angiographic findings, and response to treatment with thrombolytic therapy in patients with ischemic stroke caused by acute occlusion of the distal internal carotid artery. Methods— This is a retrospective case series from a prospectively collected stroke database for patients with acute internal carotid occlusion presenting within 6 hours of stroke onset to evaluate safety, feasibility, and response to thrombolytic therapy. The University Hospital–based brain attack database was reviewed over a 5-year period. Demographics, clinical features, stroke mechanisms, severity, imaging findings, type of thrombolysis, treatment responses, mortality, and long-term outcome using modified Rankin Scale and Barthel Index were determined. The short-term outcome was assessed using the National Institutes of Health Stroke Scale (NIHSS). Acute thrombolytic therapy was administered using recombinant tissue plasminogen activator or urokinase given intra-arterially or in combination with intravenous (IV) routes. Results— Two hundred seven patients treated with thrombolysis between 1995 and 2000 were reviewed, and of these, 101 were studied with cerebral angiography. Eighteen patients were identified with acute ischemic stroke and ipsilateral occlusion of the distal internal carotid artery. Time to treatment was the most powerful predictor of response to thrombolytic therapy (P <0.001). The response to therapy also correlated well with the severity of the initial clinical deficit as judged by the NIHSS (P <0.001). There was no difference in recanalization rate, symptomatic hemorrhage, and NIHSS for IV/intra-arterial (IA) versus IA alone (P =NS). Complete angiographic recanalization was accomplished in 80% of those who received combined IV/IA thrombolysis and in 62% of those who received IA therapy (P =NS). Those with distal occlusions extending to the middle and anterior cerebral arteries were the least likely to respond to thrombolysis. Symptomatic intracerebral hemorrhage occurred in 20% of the patients receiving IV/IA therapy, and in 15% of the IA only (P =NS). At 24 hours, the NIHSS dropped by 3 points in the IA group and 4 points in the IV/IA group (P =NS). Mild disability with independence was found in 77% of the survivors at 3-month follow-up. The mortality rate was 50% in this group despite thrombolysis. Conclusions— Thrombolytic therapy using a combination of IV and IA routes and using the IA-only route may be effective in improving outcome for the patients suffering from occlusion of the distal internal carotid artery. Shorter intervals between onset and treatment seem to be correlated with higher rate of recanalization and improved outcome.

Predictors of clinical improvement, angiographic recanalization, and intracranial hemorrhage after intra-arterial thrombolysis for acute ischemic stroke.

BACKGROUND AND PURPOSE We sought to evaluate predictors of clinical outcome, angiographic success, and adverse effects after intra-arterial administration of urokinase for acute ischemic stroke. METHODS We designed a Brain Attack program at University Hospitals of Cleveland for diagnosis and treatment of patients presenting within 6 hours of onset of neurological deficit. Patients with ischemia referable to the carotid circulation were treated with intra-arterial urokinase. Angiographic recanalization was assessed at the end of medication infusion. Intracerebral hemorrhage was investigated immediately after and 24 hours after treatment. Stroke severity was determined, followed by long-term outcome. RESULTS Fifty-four patients were treated. There was improvement of >/=4 points on the National Institutes of Health Stroke Scale from presentation to 24 hours after onset in 43% of the treated patients, and this was related to the severity of the initial deficit. Forty-eight percent of patients had a Barthel Index score of 95 to 100 at 90 days, and total mortality was 24%. Cranial CT scans revealed intracerebral hemorrhage in 17% of patients in the first 24 hours, and these patients had more severe deficits at presentation. Eighty-seven percent of patients received intravenous heparin after thrombolysis, and 9% of them developed a hemorrhage into infarction. Angiographic recanalization was the rule in complete occlusions of the horizontal portion of the middle cerebral artery, but distal carotid occlusions responded less well to thrombolysis. CONCLUSIONS The intra-arterial route for thrombolysis allows for greater diagnostic precision and achievement of a higher concentration of the thrombolytic agent in the vicinity of the clot. Disadvantages of this therapy lie in the cost and delay. Severity of stroke and site of angiographic occlusion may be important predictors of successful treatment.

Very late thrombosis of a pipeline embolization device construct: Case report

BACKGROUND The Pipeline embolization device (PED) is a new endoluminal construct designed to exclude aneurysms from the parent cerebrovasculature. We report the very late (>1 year) thrombosis of a PED construct placed for the treatment of a left vertebral aneurysm. CLINICAL PRESENTATION A patient with an occluded right vertebral artery and a large, fusiform intracranial left vertebral artery aneurysm was treated with PED and coil reconstruction. A durable, complete occlusion of the aneurysm was confirmed with control angiography at 1 year. The patient remained neurologically normal for 23 months until he experienced a transient visual disturbance followed weeks later by a minor brainstem stroke. INTERVENTION Imaging evaluation showed thrombosis of the PED construct with complete occlusion of the left vertebral artery. After this stroke, he was initially treated with dual antiplatelet therapy and was then converted to warfarin. The patient remained neurologically stable for 5 months until he experienced progressive basilar thrombosis that ultimately resulted in a fatal stroke. CONCLUSION The PED represents a promising new endovascular technology for the treatment of cerebral aneurysms; however, as an investigational device, long-term follow-up data are sparse at this point. The etiology of the very late thrombosis of the PED construct in this case remains unknown; however, this report underscores the need for a continued, careful systematic evaluation and close long-term follow-up of treated patients.

Predictors of Hyperacute Clinical Worsening in Ischemic Stroke Patients Receiving Thrombolytic Therapy

Background and Purpose— Although long-term outcome determinants in acute ischemic stroke (AIS) patients have been defined, less is known about those predicting hyperacute worsening after thrombolytic therapy (TT). We investigated predictors of short-term clinical worsening (National Institutes of Health Stroke Scale [NIHSS] change ≥4 within 24 hours of admission). Methods— We studied 201 AIS patients who received TT within 6 hours of symptom onset. We determined baseline demographics, comorbidities, NIHSS at baseline and at 24 hours after TT, head computed tomography scan before and within 24 hours after TT, and angiographic recanalization in patients treated with intra-arterial (IA) thrombolysis. Significance of relationships was evaluated by t test or Wilcoxon signed rank sum test. Logistic regression model (LRM) was fitted to determine independence of significant variables. Results— Of 201 patients, 13% worsened, 39% improved, and 48% remained unchanged 24 hours after TT. Most patients (72%) received IA thrombolysis. Patients who deteriorated, compared with those who improved, were more likely to have complicating intracranial hemorrhage (ICH; P <0.001), absent recanalization (P =0.026), and higher blood glucose (BG; P =0.049). Hyperglycemia (>150 mg/dL) was greater in patients who worsened even in presence of recanalization (P =0.004, odds ratio [OR] 6.47). LRM showed that adjusted OR for increased risk of bad outcome and mortality for an increase of BG by 50 mg/dL is 1.56 and 1.38, respectively. Conclusions— Hyperglycemia and ICH are independent predictors of hyperacute worsening in AIS patients receiving TT. Although recanalization is the purpose of IA thrombolysis, its impact on clinical improvement may not be apparent without strict BG control.

The POST trial: initial post-market experience of the Penumbra system: revascularization of large vessel occlusion in acute ischemic stroke in the United States and Europe

Background and purpose The purpose of this study was to assess the initial post-market experience of the device and how it is compared with the Penumbra Pivotal trial used to support the 510k application. Methods A retrospective case review of 157 consecutive patients treated with the Penumbra system at seven international centers was performed. Primary endpoints were revascularization of the target vessel (TIMI score of 2 or 3), good functional outcome as defined by a modified Rankin scale (mRS) score of ≤2 and incidence of procedural serious adverse events. Results were compared with those of the Penumbra pivotal trial. Results A total of 157 vessels were treated. Mean baseline values at enrollment were: age 65 years, NIHSS score 16. After use of the Penumbra system, 87% of the treated vessels were revascularized to TIMI 2 (54%) or 3 (33%) as compared with 82% reported in the Pivotal trial. Nine procedural serious adverse events were reported in 157 patients (5.7%). All-cause mortality was 20% (32/157), and 41% had a mRS of ≤2 at 90-day follow-up as compared with only 25% in the Pivotal trial. Patients who were successfully revascularized by the Penumbra system had significantly better outcomes than those who were not. Conclusion Initial post-market experience of the Penumbra system revealed that the revascularization rate and safety profile of the device are comparable to those reported in the Pivotal trial. However, the proportion of patients who had good functional outcome was higher than expected.

Endovascular administration after intravenous infusion of thrombolytic agents for the treatment of patients with acute ischemic strokes.

OBJECTIVE To determine the feasibility of combined intravenous and intra-arterial thrombolytic therapy for acute ischemic strokes and to evaluate its associated risks, using magnetic resonance imaging as a triage tool. Intravenous treatment followed by intra-arterial infusion may increase the rate of recanalization and lead to better clinical results, with reduced frequency of intracranial hemorrhage. METHODS Our Brain Attack Team evaluated patients who presented within 3 hours after symptom onset. Patients who did not demonstrate improvement and exhibited no evidence of intracranial hemorrhage on head computed tomographic scans were treated with intravenously administered recombinant tissue plasminogen activator (0.6 mg/kg) and underwent emergency magnetic resonance imaging of the head. T2-weighted turbo-gradient and spin echo and echo-planar diffusion- and perfusion-weighted imaging scans were obtained. Patients with evidence of imaging abnormalities indicating acute cortical infarction underwent cerebral angiography. After determination of vessel occlusion, intra-arterially administered urokinase (up to 750,000 units) or intra-arterially administered recombinant tissue plasminogen activator (maximal dose, 0.3 mg/kg) was used to achieve recanalization. RESULTS We treated 45 patients with this protocol. The mean age was 67 ± 13 years, and 58% of the patients were women. There was a significant improvement in National Institutes of Health Stroke Scale scores after treatment. There was good correlation between abnormal perfusion-weighted imaging findings and cerebral angiographic findings (complete vessel occlusion). The incidence of symptomatic intracranial hemorrhage was 4.4% in this cohort. Seven patients died in the hospital, and the majority of survivors (77%) experienced good outcomes (Barthel index of ≥95) 3 months after treatment. CONCLUSION Our data demonstrate that this protocol is feasible and that combined intravenous and intra-arterial thrombolysis to treat acute ischemic strokes is sufficiently safe to warrant further evaluation.

Older age does not increase risk of hemorrhagic complications after intravenous and/or intra-arterial thrombolysis for acute stroke.

BACKGROUND The elderly have significantly higher incidence of ischemic stroke and have higher mortality and morbidity compared with younger patients. Intracranial hemorrhage (ICH) after thrombolysis is one of the causes of unfavorable outcome. However, it is unclear whether age over 80 years is a predictor for hemorrhagic transformation after intravenous, intra-arterial, or a combination of both thrombolytic therapies. METHODS A database of 488 consecutive patients with ischemic stroke who received thrombolytic therapy was analyzed using logistic regression model to determine whether factors such as age over 80 years, demographic characteristics, onset to treatment time, severity of neurologic deficits, route of administration, blood glucose, or mean arterial pressure were associated with symptomatic ICH. RESULTS The rates of symptomatic hemorrhage were 12.82% and 10.4% in older and younger groups, respectively. The odds of symptomatic hemorrhage after thrombolytic therapy for patients over 80 years of age after adjusting for route of administration, National Institutes of Health Stroke Scale score, mean arterial pressure, and glucose was not significantly different from that of the younger age group (odds ratio [OR] = 1.64; 95% confidence interval [CI]: 0.729-3.66). Hyperglycemia (>150 mg/dL) was associated with increased odds of symptomatic ICH (OR = 2.32; 95% CI: 1.09-4.93). Patients older than 80 years had similar rates of recanalization (OR = 0.8; 95% CI: 0.4-1.8) and rates of asymptomatic ICH (OR = 2.40; 95% CI: 0.89-6.5). CONCLUSIONS Risks of ICH after thrombolysis for acute ischemic stroke are similar in patients over and under 80 years of age. Our data suggest that the decision to provide thrombolytic therapy should not be solely based on patients age.

Embolectomy for stroke with emergent large vessel occlusion (ELVO): report of the Standards and Guidelines Committee of the Society of NeuroInterventional Surgery

Stroke is the leading cause of adult disability in North America and is the fifth most common cause of death.1 ,2 The natural history of patients with acute ischemic stroke and occlusion of a major intracranial vessel such as the internal carotid artery (ICA), middle cerebral artery (MCA), or basilar artery is dismal, with high rates of mortality and low rates of disability-free survival.3 ,4 We introduce the term ‘Emergent Large Vessel Occlusion (ELVO)’ to describe this clinical scenario. Among acute ischemic stroke, ELVO accounts for the greatest proportion of patients with long-term disability. For the past two decades the use of endovascular therapy has been performed in many centers across the world. The therapies have spanned from infusion of thrombolytic agents5 ,6 to mechanical embolectomy with the introduction of first-generation devices,7 ,8 aspiration-based embolectomy techniques,9 ,10 and the use of stent-retriever based procedures.11 ,12 However, these embolectomy trials were single-arm trials demonstrating safety of the procedure and technique or superiority over another, without direct comparison with standard medical therapy alone. In the past 3 years, several major trials have been published comparing endovascular therapy with standard medical therapy alone. The purpose of this document is to summarize the results of these trials and synthesize the level of evidence supporting the use of embolectomy in patients with ELVO. This document was prepared by the Standards and Guidelines Committee of the Society of NeuroInterventional Surgery, a multidisciplinary society representing the leaders in the field of endovascular therapy for neurovascular disease. The strength of the evidence supporting each recommendation was summarized using a scale previously described by the American Heart Association. ### Role of intravenous thrombolysis In 1996 the FDA approved the use of recombinant tissue plasminogen activator (tPA) for the treatment of acute ischemic stroke …

Early carotid artery stenting and angioplasty in patients with acute ischemic stroke.

OBJECTIVE:To determine the safety of early percutaneous endovascular carotid angioplasty and stenting (CAS) after an ischemic stroke. METHODS:The neurointerventional database was reviewed for patients who underwent CAS after an acute ischemic stroke in two university hospitals. Clinical and radiological data were reviewed. Outcomes were worsening stroke, new stroke, or stroke-related death up to 30 days after the procedure. Procedure-related complications were also documented. RESULTS:A total of 38 patients with 39 procedures were identified. The mean age was 67 ± 15 years; 31 of 38 patients were Caucasian and 24 were female. Hypertension was found in 21 patients, peripheral vascular disease in 12, diabetes in 13, and coronary artery disease in 18. The median initial National Institutes of Health Stroke Scale score was 8. The carotid artery showed severe to high-grade stenosis in 28 patients, dissection was present in 6, and the rest had an acute occlusion treated with thrombolysis followed by CAS. The mean time from stroke onset to CAS was 55 ± 34 hours. The mean degree of stenosis at baseline was 86 ± 11%. In 37 procedures, complete recanalization was achieved, defined as less than 10% residual narrowing; in 2 procedures, the residual stenosis was mild (10–20%). Neurological deterioration occurred after three procedures (7.7%), with minor nondisabling stroke in two and death from intracranial hemorrhage in one. CONCLUSION:If deemed necessary and in certain circumstances, early CAS seems to be safe after acute ischemic stroke if infarction volume is small and neurological deficit is mild.

Comparison of Combined Venous and Arterial Thrombolysis with Primary Arterial Therapy Using Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke

OBJECTIVE We sought to compare the safety and efficacy of combined intravenous (IV) and intra-arterial (IA) thrombolysis with primary IA therapy using tissue plasminogen activator for acute ischemic stroke presenting within 6 hours of symptom onset. METHODS We performed quasirandomization of a single institutions prospectively collected stroke database, comparing IV/IA (0.6 mg/kg IV < or = 60 mg, followed by 0.3 mg/kg IA < or = 30 mg) versus primary IA. Outcome measures include 90-day modified Rankin scale score, mortality, symptomatic intracerebral hemorrhage, and recanalization rates. Statistical analysis was performed using bivariate and propensity score methods. RESULTS Of 1057 patients, 41 patients were treated with IV/IA, and 55 with IA. There was significant difference in time to treatment (mean of 151 minutes for the combined group and 261 minutes for the IA, P < .0001) and arterial tissue plasminogen activator dose (17.5 mg for IV/IA v 22.8 mg for IA only, P = .05). Propensity score matching yielded 25 patients in each group. Symptomatic intracerebral hemorrhage rate was 12% in each group. Mortality was 20% in the IV/IA group versus 16% in the IA group (relative risk 1.3 [0.4-4.1], P = .7). More patients in IV/IA group had modified Rankin scale score less than or equal to 2 (odds ratio 1.6 [0.5-5.8], P = .3). Recanalization was 64% with IV/IA versus 48% with IA (odds ratio 1.9 [0.5-7.0], P = .3). CONCLUSION This study demonstrates that both combined IV/IA and primary IA recombinant tissue plasminogen activator therapy is feasible and safe in the treatment of acute ischemic stroke. Combined IV/IA therapy may be associated with an improvement in clinical outcome without a significant increase in the risk of symptomatic intracerebral hemorrhage and mortality compared with IA therapy.