Tareq Kass-Hout

Intravenous Thrombolysis and Endovascular Therapy for Acute Ischemic Stroke With Internal Carotid Artery Occlusion: A Systematic Review of Clinical Outcomes

Background and Purpose— Strokes secondary to acute internal carotid artery (ICA) occlusion are associated with extremely poor prognosis. The best treatment approach to acute stroke in this setting is unknown. We sought to determine clinical outcomes in patients with acute ischemic stroke attributable to ICA occlusion treated with intravenous (IV) systemic thrombolysis or intra-arterial endovascular therapy. Methods— Using the PubMed database, we searched for studies that included patients with acute ischemic stroke attributable to ICA occlusion who received treatment with IV thrombolysis or intra-arterial endovascular interventions. Studies providing data on functional outcomes beyond 30 days and mortality and symptomatic intracerebral hemorrhage (sICH) rates were included in our analysis. We compared the proportions of patients with favorable functional outcomes, sICH, and mortality rates in the 2 treatment groups by calculating &khgr;2 and confidence intervals for odds ratios. Results— We identified 28 studies with 385 patients in the IV thrombolysis group and 584 in the endovascular group. Rates of favorable outcomes and sICH were significantly higher in the endovascular group than the IV thrombolysis-only group (33.6% vs 24.9%, P=0.004 and 11.1% vs 4.9%, P=0.001, respectively). No significant difference in mortality rate was found between the groups (27.3% in the IV thrombolysis group vs 32.0% in the endovascular group; P=0.12). Conclusions— According to our systematic review, endovascular treatment of acute ICA occlusion results in improved clinical outcomes. A higher rate of sICH after endovascular treatment does not result in increased overall mortality rate.

Flow Diverters for Intracranial Aneurysms

Flow diverters (pipeline embolization device, Silk flow diverter, and Surpass flow diverter) have been developed to treat intracranial aneurysms. These endovascular devices are placed within the parent artery rather than the aneurysm sac. They take advantage of altering hemodynamics at the aneurysm/parent vessel interface, resulting in gradual thrombosis of the aneurysm occurring over time. Subsequent inflammatory response, healing, and endothelial growth shrink the aneurysm and reconstruct the parent artery lumen while preserving perforators and side branches in most cases. Flow diverters have already allowed treatment of previously untreatable wide neck and giant aneurysms. There are risks with flow diverters including in-stent thrombosis, perianeurysmal edema, distant and delayed hemorrhages, and perforator occlusions. Comparative efficacy and safety against other therapies are being studied in ongoing trials. Antiplatelet therapy is mandatory with flow diverters, which has highlighted the need for better evidence for monitoring and tailoring antiplatelet therapy. In this paper we review the devices, their uses, associated complications, evidence base, and ongoing studies.

Is Bridging with Intravenous Thrombolysis of Any Benefit in Endovascular Therapy for Acute Ischemic Stroke

OBJECTIVE Large vessel occlusions with heavy clot burden are less likely to improve with intravenous (IV) thrombolysis alone. The purpose of this study was to show whether a combination of IV thrombolysis and endovascular therapy was superior to endovascular treatment alone. METHODS Data for 104 patients with acute large artery occlusion treated between 2005 and 2010 were reviewed. Forty-two received endovascular therapy in combination with IV thrombolysis (bridging group), and 62 received endovascular therapy only. Clinical outcome, mortality rate, and symptomatic intracranial hemorrhage (sICH) rate were compared between the two groups. RESULTS The two groups had similar demographic and vascular risk factor distribution, as well as National Institutes of Health Stroke Scale score on admission (mean±SD: 14.8±4.7 and 16.0±5.3; P=0.23). No difference was found in Thrombolysis in Myocardial Infarction recanalization rates (score of 2 or 3) after combined or endovascular therapy alone (83.33% and 79.03%; P=0.585). Favorable outcome, defined as a modified Rankin Scale score of <2 at 90 days, also did not differ between the bridging group and the endovascular-only group (37.5% and 32.76%; P=0.643). There was no difference in mortality rate (19.04% and 29.03%; P=0.5618) and sICH rate (11.9% and 9.68%; P=0.734). A significant difference was found in mean time from symptom onset to treatment in the bridging group and the endovascular-only group (227±88 min vs. 125±40 min; P<0.0001). CONCLUSION Combining IV thrombolysis with endovascular therapy resulted in similar outcome, revascularization, sICH, and mortality rates compared with endovascular therapy alone. Prospective clinical studies comparing both treatment strategies in acute ischemic stroke are warranted.

Intracerebral hemorrhage secondary to intravenous and endovascular intraarterial revascularization therapies in acute ischemic stroke: an update on risk factors, predictors, and management

Intracerebral hemorrhage (ICH) secondary to intravenous and intraarterial revascularization strategies for emergent treatment of acute ischemic stroke is associated with high mortality. ICH from systemic thrombolysis typically occurs within the first 24-36 hours of treatment initiation and is characterized by rapid hematoma development and growth. Pathophysiological mechanisms of revascularization therapy-induced ICH are complex and involve a combination of several distinct processes, including the direct effect of thrombolytic agents, disruption of the blood-brain barrier secondary to ischemia, and direct vessel damage from wire and microcatheter manipulations during endovascular procedures. Several definitions of ICH secondary to thrombolysis currently exist, depending on clinical or radiological characteristics used. Multiple studies have investigated clinical and laboratory risk factors associated with higher rates of ICH in this setting. Early ischemic changes seen on noncontrast CT scanning are strongly associated with higher rates of hemorrhage. Modern imaging techniques, particularly CT perfusion, provide rapid assessment of hemodynamic parameters of the brain. Specific patterns of CT perfusion maps can help identify patients who are likely to benefit from revascularization or to develop hemorrhagic complications. There are no established guidelines that describe management of revascularization therapy-induced ICH, and great variability in treatment protocols currently exist. General principles that apply to the management of spontaneous ICH might not be as effective for revascularization therapy-induced ICH. In this article, the authors review current knowledge of risk factors and radiological predictors of ICH secondary to stroke revascularization techniques and analyze medical and surgical management strategies for ICH in this setting.

Platelet function inhibitors and platelet function testing in neurointerventional procedures

Over the past decade there has been a growing use of intracranial stents for the treatment of both ischemic and hemorrhagic cerebrovascular disease, including stents to assist in the remodeling of the neck of aneurysms as well as the use of flow diverting devices for aneurysm treatment. With this increase in stent usage has come a growing need for the neurointerventional (NI) community to understand the pharmacology of medications used for modifying platelet function, as well as the testing methodologies available. Platelet function testing in NI procedures remains controversial. While pre-procedural antiplatelet assays might lead to a reduced rate of thromboembolic complications, little evidence exists to support this as a standard of care practice. Despite the routine use of dual antiplatelet therapy (DAT) with aspirin and a P2Y12 receptor antagonist (such as clopidogrel, prasugrel, or ticagrelor) in most neuroembolization procedures necessitating intraluminal reconstruction devices, thromboembolic complications are still encountered.1–3 Moreover, DAT carries the risk of hemorrhagic complications, with intracerebral hemorrhage (ICH) being the most potentially devastating.4 ,5 Light transmission aggregometry (LTA) is the gold standard to test for platelet reactivity, but it is usually expensive and may not be easily obtainable at many centers. This has led to the development of point-of-care assays, such as the VerifyNow (Accumetrics, San Diego, California, USA), which correlates strongly with LTA and can reliably measure the degree of P2Y12 receptor inhibition.6–9 VerifyNow results are reported in P2Y12 reaction units (PRUs), with a lower PRU value corresponding to a higher level of P2Y12 receptor inhibition and, presumably, a lower probability of platelet aggregation, and a higher PRU value corresponding to a lower level of P2Y12 receptor inhibition and, hence, a higher chance of platelet activation and aggregation. While aspirin resistance is perhaps less common, clopidogrel resistance may be more challenging as …

Early carotid angioplasty and stenting may offer non-inferior treatment for symptomatic cases of carotid artery stenosis

Objective Early intervention is desirable in patients presenting with stroke or transient ischemic attack (TIA) referable to carotid artery stenosis because of the high incidence of recurrent ischemic events within 48 h post-ictus. However, the optimal timing of performing carotid angioplasty and stenting (CAS) in these patients remains unclear amid concerns for an elevated risk of perioperative complications. The primary outcome of this study was the combined incidence of major perioperative complications (stroke, myocardial infarction (MI), death) based on timing of CAS relative to symptom onset. Methods A prospectively maintained database of all neuroendovascular procedures at our hospital was searched for consecutive cases of extracranial internal CAS procedures performed for symptomatic atherosclerotic carotid stenosis between January 2009 and January 2012. Rates of perioperative complications including 30-day stroke, MI and death were assembled in a total of 221 patients. Results The primary outcome was not statistically different among groups stratified based on intervention timing, with a combined incidence of stroke, MI or death of 7.1% in patients treated within 2 days, 4.5% in patients treated between days 3 and 7, 2.8% in patients treated between days 8 and 14 and 3.7% in patients treated between days 15 and 90 (p=0.749, Fisher exact test). Conclusions Our results support the conclusion that early CAS (within 2 days) carries no additional risks compared with CAS after 2 days or any other timing of the intervention up to 90 days. Early CAS may represent a reasonable option for acute revascularization to minimize the risk of perioperative stroke and overall perioperative complications.

A Novel Approach to Diagnose Reversible Cerebral Vasoconstriction Syndrome: A Case Series

BACKGROUND Reversible cerebral vasoconstriction syndrome (RCVS) is classically diagnosed based on the presence of severe thunderclap headache, focal neurologic symptoms, and the radiographic findings of reversible diffuse segmental cerebral vasoconstriction. We present a diagnostic test that may assist in the clinical diagnosis and facilitate treatment. METHODS From October 1, 2010, to August 1, 2013, we identified consecutive patients who presented with a presumptive diagnosis of RCVS and underwent cerebral diagnostic angiography with intra-arterial (IA) vasodilator therapy. Medical records including clinical presentation, radiographic, and angiographic images were all reviewed. RESULTS We identified a total of 7 patients (4 females; age range, 22-56; mean, 45 years) who met our inclusion criteria. Four patients received a combination of milrinone and nicardipine infusion either in the internal carotid arteries or in the left vertebral artery; the remaining patients received IA therapy solely with either nicardipine or milrinone. Five patients had a positive angiographic response, defined as significant improvement or resolution of the blood vessels irregularities. All 5 patients had a definite discharge diagnosis of RCVS. The remaining 2 patients had a negative angiographic response and based on their clinical and radiographic course had a final diagnosis of intracranial atherosclerotic disease. CONCLUSIONS Our small case series suggest that IA administration of vasodilators is safe and may aid in distinguishing vasodilator responsive syndromes such as RCVS from other causes. Further study is required with long-term clinical outcome to determine the utility of this diagnostic test.

Blood Pressure Management and Evolution of Thrombolysis-associated Intracerebral Hemorrhage in Acute Ischemic Stroke

BACKGROUND There is limited knowledge on the radiographic features of thrombolysis-induced hemorrhage. The factors that influence early hematoma expansion have not been elucidated. METHODS Patients presenting with a symptomatic intracerebral hemorrhage (ICH) as a result of intravenous (IV) thrombolysis with tissue plasminogen activator (tPA) for acute ischemic stroke and had noncontrast computed tomographic (CT) scans of the head were included in this retrospective study. Calculation of hematoma volumes was obtained. Analysis of covariance was used to evaluate for the effect of baseline blood pressure (BP) on initial hematoma volume and further growth. RESULTS Of 267 patients who were treated with intravenous tPA for acute ischemic stroke at our facility between January 1, 2005 and December 31, 2009, 17 patients developed symptomatic ICH and were included in the final analysis. There was a positive correlation between baseline level of systolic BP after thrombolysis and initial hematoma volume (r = 0.46; P = .03) but not for the diastolic BP (r = 0.07; P = .40). There was a significant increase in mean hematoma volume expansion when comparing results between the first and second CT scans (median 9 hours, 22 minutes; 14.9 ± 19.6 cm(3) to 26.0 ± 26.7 cm(3); P = .04). There was also a negative association between the reduction of systolic BP and hematoma growth (r = -0.67; P = .02), but no correlation with change in diastolic BP (r = -0.22; P = .28). CONCLUSIONS Once diagnosed, thrombolysis-induced symptomatic ICH undergoes significant early expansion in size. Systolic BP may play a role in hematoma expansion.

Intravenous heparin for the treatment of intraluminal thrombus in patients with acute ischemic stroke: a case series

Background and Objectives Current American Stroke Association/American Heart Association recommendations on the management of acute ischemic stroke do not recommend the early use of heparin because of an increased risk of bleeding complications. However, for select patients, such as those with strokes associated with non-occlusive intraluminal thrombus, intravenous heparin might prove to be beneficial. Methods A retrospective analysis of acute ischemic stroke cases associated with non-occlusive intraluminal thrombus of intracranial and extracranial arteries in the corresponding vascular territories was conducted to identify patients in whom treatment with intravenous heparin resulted in near-complete or complete lysis of the thrombus. Imaging findings from CT perfusion and angiography, MRI, and/or digital subtraction angiography were used to describe the location of intraluminal thrombus immediately before and after treatment with intravenous heparin. Results 18 patients with nonocclusive intraluminal thrombus confirmed by CT angiography (CTA) received treatment with intravenous heparin alone (median duration 3.5 days; range 1–8 days). The median National Institutes of Health stroke scale score was 2.5 (range 0–15) on admission and 1 (range 0–9) at discharge. Nine patients had complete lysis, and nine patients had partial lysis of the thrombus with improved flow distal to the location of the thrombus. None of the patients developed intracranial hemorrhage. Conclusion For strokes associated with intraluminal thrombus, intravenous heparin might prove to be an effective treatment strategy. Further studies are necessary to evaluate the efficacy and safety of treatment with intravenous heparin in those patients.

Outcomes in patients with acute ischemic stroke from proximal intracranial vessel occlusion and NIHSS score below 8

Objective Acute ischemic stroke due to proximal intracranial vessel occlusion is associated with poor prognosis and neurologic outcomes. Outcomes specifically in patients with stroke due to these occlusions and lower National Institutes of Health Stroke Scale (NIHSS) scores (0–7 range) have not been described previously. Methods We retrospectively reviewed discharge outcomes (reported in our ‘Get With the Guidelines-Stroke’ database) in patients with an admission NIHSS score of 0–7 due to proximal intracranial large vessel occlusion (based on CT angiography results) who were excluded from receiving intravenous (IV) thrombolysis with recombinant tissue plasminogen activator and endovascular intra-arterial (IA) stroke interventions. Results Among the 204 patients included in our analysis, younger age and lower admission NIHSS score (0–4 range) were strong predictors of good outcome (defined as ability to ambulate independently) at discharge whereas female sex was a predictor of poor outcome. There was no significant difference between cerebrovascular risk factors, specific sites of occlusion, or presenting symptoms and outcomes at discharge. There was great variability in functional outcomes at discharge and discharge disposition (home versus acute or subacute facility or nursing home versus death/hospice) with a trend toward worse outcomes in patients with higher (5–7 range) NIHSS scores on admission. Conclusions Patients with acute stroke due to large vessel occlusion and low admission NIHSS scores (0–7 range) may have poor functional outcomes at discharge. These patients, if not eligible for IV thrombolysis, might benefit from IA revascularization therapies.