Yazan J. Alderazi

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.

A Model to Prevent Fibrinolysis in Patients with Stroke Mimics

BACKGROUND Many patients with stroke-mimicking conditions receive treatment with intravenous fibrinolysis (IVF), a treatment associated with potentially serious complications. We sought to determine if any clinical or radiographic characteristics can help predict stroke mimics among IVF candidates. METHODS This retrospective study was carried out at a single institution. Patients treated with intravenous recombinant tissue plasminogen activator (rt-PA; n = 193) were divided into 3 categories: acute ischemic stroke (n = 142), aborted stroke (n = 21), and stroke mimics (n = 30). Analysis of variance and the chi-square test were used to assess differences, while logistic regression models were computed to predict groups. RESULTS Mimics treated with rt-PA did not experience complications (intracranial bleeding, systemic hemorrhage, or angioedema), and had better neurologic and functional outcomes than stroke patients (P < .05). Several variables helped differentiate strokes from mimics, including atherosclerosis on computed tomographic angiography (odds ratio [OR] 23.6; 95% confidence interval [CI] 8.4-66.2), atrial fibrillation (OR 11.4; 95% CI 1.5-86.3), age >50 years (OR 7.2; 95% CI 2.8-18.5), and focal weakness (OR 4.15; 95% CI 1.75-9.8). Other variables decreased chances of stroke: migraine history (OR 0.05; 95% CI 0.01-0.4), epilepsy (OR 0.13; 95% CI 0.02-0.8), paresthesia (OR 0.1; 95% CI 0.04-0.3), and precordialgia (OR 0.045; 95% CI 0.002-0.9). A regression model using focal weakness, computed tomographic angiography findings, and precordialgia had a 90.2% predictive accuracy. CONCLUSIONS IVF has low complication rates in stroke mimics. Certain clinical characteristics appear predictive of stroke mimics, particularly normal computed tomographic angiography. If confirmed, this may help prevent giving IVF to patients without stroke.

Acute Antithrombotic Treatment of Ischemic Stroke

Antithrombotic medication is a cornerstone of acute ischemic stroke treatment and secondary prevention. The efficacy of thrombolysis with alteplase in acute stroke has been demonstrated in several clinical trials. This safe and costeffective therapy has transformed the practice of stroke care and has led to subsequent trials of other antithrombotic medications for treatment of ischemic stroke in the acute phase. These antithrombotics include thrombolytic, antiplatelet and anticoagulant agents. While, no other medication has yet demonstrated adequate efficacy, our current and evolving understanding of infarct expansion, ischemic penumbra, collateral circulation and the blood brain barrier is allowing testing of antithrombotic medications tailored to individual patient pathophysiology in clinical trials. This understanding accompanies developments in neuroimaging and organization of stroke care that allow for wide-spread recruitment in these trials. Alteplase remains the mainstay treatment of arterial acute ischemic stroke; however, anticoagulation is the standard therapy for cerebral venous sinus thrombosis. Antithrombotic use in acute stroke, arterial and venous, has demonstrated efficacy but leaves many questions unanswered. This patient population is a fertile ground for novel research, especially as it relates to; combination antithrombotic therapy, combination of pharmacological and mechanical thrombolysis, and the transition to secondary prevention. Here we review the current antithrombotics in the acute phase of ischemic stroke highlighting the evidence-base and areas of uncertainty.

Clotting Factors to Treat Thrombolysis-related Symptomatic Intracranial Hemorrhage in Acute Ischemic Stroke

BACKGROUND Symptomatic intracranial hemorrhage (sICH) occurs uncommonly after ischemic stroke therapy with tissue plasminogen activator (tPA). Clotting factor administration may be a treatment option. OBJECTIVE To determine if treatment with clotting factors (fresh frozen plasma [FFP] or cryoprecipitate) was associated with improved outcomes in sICH. METHODS We conducted a retrospective cohort study within University of Texas at Houston Stroke registry involving consecutive patients from February 1, 2007, to June 30, 2011, with tPA-related sICH, including cases with subsequent intra-arterial therapy. Outcomes were Modified Rankin Scale (mRS) score at discharge, death, and hematoma expansion. RESULTS Of 921 patients treated with tPA, 48 (5.2%) had sICH and 45 met criteria for the study. Nineteen patients received clotting factors (42.2%; 18 received FFP and 7 received cryoprecipitate), whereas 26 (57.8%) patients received conservative management without clotting factors. None of the patients treated with clotting factors and only 2 of those who did not receive clotting factors had a good outcome, mRS score of 2 or less. All the patients treated with clotting factors and most of those not treated were left bedridden or dead (mRS score 4-6), 19 (100%) versus 22 (85%). Mortality was 9 (47.4%) versus 9 (34.6%), respectively. There was no difference in hematoma expansion between the 2 groups. CONCLUSIONS We found no evidence that treatment for sICH with clotting factors has a favorable effect on clinical or radiological outcomes. However, the sample was small because of the low frequency of sICH. New treatments are urgently needed for this uncommon yet serious condition.

Neurointerventional Stenting and Antiplatelet Function Testing: To Do or Not to Do?

Background and Purpose: Platelet function testing in neurointerventional (NI) procedures is still controversial. We compared the clinical outcomes between antiplatelet responders and nonresponders based on the results of the VerifyNow (VN) testing method. Methods: This is a retrospective single-center analysis of all consecutive patients who underwent NI stenting procedures from January 2007 through July 2013 and had documented preprocedural aspirin (ASA) and clopidogrel VN assays. Patients were divided into two groups based on their responsiveness to antiplatelet. Baseline characteristics, good functional outcome measured by the modified Rankin Scale (mRS) at 90 days, combined procedural complication rate defined as postprocedural stroke, in-stent thrombosis, and intraoperative rupture were compared between the two groups. Results: Our cohort included 37 patients: 26 were in the responder group (RG) and 11 were in the nonresponder group (NRG). Baseline characteristics were similar between the two groups. Even though the combined complication rate was similar between the two groups [NRG: 2/11 (18%) vs. RG: 2/26 (7%); p = 0.33], there was a trend for a higher rate of good functional outcome (90-day mRS: 0-2) in the RG (22/22, 100%) as compared to the NRG (8/10, 80%) (p = 0.0907). Conclusion: Overall, utilizing the VN antiplatelet function testing did not significantly change the clinical outcome after the NI procedures. Larger randomized trials are warranted to provide a better understanding of the utility of the antiplatelet testing in NI stenting procedures.

Clinical outcomes after intravenous fibrinolysis in cryptogenic strokes with or without patent foramen ovale.

BACKGROUND Pivotal clinical trials suggest that intravenous (IV) recombinant tissue plasminogen activator (rt-PA) benefits stroke patients regardless of the underlying etiology. Paradoxical strokes, presumed to be caused by fibrin-rich clots originating in the venous circulation, may respond better to fibrinolysis than other ischemic stroke subtypes. In this study, we compared the response with IV rt-PA in paradoxical stroke patients and other stroke subtypes. METHODS In total, 486 patients treated with IV rt-PA at a single institution were retrospectively reviewed. Adjudication of stroke mechanism was based on chart review. Five major stroke mechanisms--cardioembolic, artery-to-artery emboli, lacunar, cryptogenic, and paradoxical--were identified by final diagnosis from chart reviews. Mimics, undefined etiology, and defined etiology not falling into the major mechanisms were excluded. Analysis of variance and general linear model were used to assess the differences between groups. RESULTS A total of 323 patients were analyzed. We found significant differences in clinical outcome between stroke mechanisms, including discharge National Institutes of Health Stroke Scale (NIHSS) (P=.007), discharge Rankin (P=.011), discharge disposition (P=.000), and infarct volume (P=.007). Post hoc analysis showed that cardioembolic patients had the worst outcomes (discharge NIHSS score 11.12±12.26), whereas paradoxical strokes had the best outcomes (discharge NIHSS score 3.67±4.90), but these did not approach statistical significance. However, regression analysis showed that 4 variables--congestive heart failure, admission NIHSS, age, and mean infarct volume--rather than stroke mechanism were the true predictors of poor outcome. CONCLUSIONS Paradoxical strokes had better outcomes after IV fibrinolysis than other ischemic stroke subtypes, but this difference is attributable to younger age and milder stroke severity on presentation.

Arteriovenous Malformations in the Pediatric Population: Review of the Existing Literature

Arteriovenous malformations (AVMs) in the pediatric population are relatively rare but reportedly carry a higher rate of rupture than in adults. This could be due to the fact that most pediatric AVMs are only detected after rupture. We aimed to review the current literature regarding the natural history and the clinical outcome after multimodality AVM treatment in the pediatric population, as optimal management for pediatric AVMs remains controversial. A multidisciplinary approach using multimodality therapy if needed has been proved to be beneficial in approaching these lesions in all age groups. Microsurgical resection remains the gold standard for the treatment of all accessible pediatric AVMs. Embolization and radiosurgery should be considered as an adjunctive therapy. Embolization provides a useful adjunct therapy to microsurgery by preventing significant blood loss and to radiosurgery by decreasing the volume of the AVM. Radiosurgery has been described to provide an alternative treatment approach in certain circumstances either as a primary or adjuvant therapy.

Impact of Protocol Deviations in Acute Ischemic Stroke Treated With Intravenous rt-PA Within 4.5 Hours After Symptom Onset.

Background: There is limited experience in the community with intravenous tissue plasminogen activator (rt-PA) administered 3 to 4.5 hours after acute ischemic stroke (AIS) onset. Many patients do not meet entry criteria of pivotal clinical trials because of severe stroke, age >80, severe hypertension (sHTN), or history of previous stroke and diabetes. Whether rt-PA benefits these patients is unclear. Thus, we investigated the outcomes of stroke patients treated with rt-PA with or without these adverse clinical characteristics. Methods: Chart review of patients with AIS treated with intravenous rt-PA at a single institution. Outcomes at discharge were compared between patients with severe stroke, age >80, sHTN, or previous stroke/diabetes and those without these characteristics. Good outcome was defined as modified Rankin score (mRS) of 0 to 1. Analysis of variance and t tests were used to compare the outcomes. Results: Of the 118 cases analyzed, 103 (87%) were treated ≤3 hours and 15 (13%) between 3 and 4.5 hours. Sixty-three (53%) patients had severe stroke, age >80, sHTN, or previous stroke/diabetes, whereas 55 (47%) did not. Compared to controls, patients with these adverse characteristics were less likely to have good outcomes (35% vs 56%, p = .02). No patients treated within the 3- to 4.5-hour window experienced symptomatic intracranial hemorrhage (sICH). Eight patients treated between 3 and 4.5 hours had severe stroke, age >80, sHTN, or previous stroke/diabetes. Of these, 6 had poor outcomes. Conclusions: In a highly selected group of patients treated with intravenous rt-PA, lack of adherence to current guidelines did not improve stroke outcomes. This was related to more severe strokes at baseline, not sICH. Prospective studies of this patient group are needed.

The importance of specialized stroke care for patients with TIA

TIA as a medical emergency requires early appropriate management to minimize the risk of adverse outcomes.1 Traditionally, we addressed this challenge by admitting all patients with TIA to the hospital, presuming that this would offer the best care available with the least possible delay. Over the past decade, increasing evidence has emerged that not all patients with TIA require hospital admission, and that some or even most patients can be safely managed in the outpatient setting.2

Endovascular Therapy for Acute Ischemic Stroke: Time to Enter a New Era in Stroke Management

Endovascular thrombectomy in acute ischemic stroke (AIS) generated significant controversy regarding its role in achieving good clinical outcome. This was especially palpable as of February 2013 when 3 prospective randomized controlled trials (Interventional Management of Stroke [IMS III] (Ref 2), Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy [MR RESCUE] (Ref 6), and SYNTHESIS-Expansion (Ref 4)) were presented in the International Stroke Conference and simultaneously published in the New England Journal of Medicine —. None of these trials were able to demonstrate clinical outcome benefit of endovascular therapy versus medical management, which was the standard of care in AIS. Despite the significant design flaws in all of these trials (which was mostly due to slow patient enrollment, slow endovascular therapy delivery, older thrombectomy devices, and poor target lesion selection), the results of these trials had a significant effect on triaging and referral pattern of patients with emergent large vessel occlusion (ELVO) acute ischemic stroke. This motivated stroke investigators around the globe to conduct trials with improved design parameters to avoid the shortcomings reported in the preceding trials. Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) (1) was the first prospective randomized controlled trial to prove superiority of endovascular intervention to medical therapy in ELVO strokes. This trial was conducted in 16 centers in the Netherlands, included 500 patients, and compared endovascular therapies with medical management for patients with ELVO (233 assigned to intra-arterial [IA] treatment and 267 to usual care alone). Most patients in both groups received intravenous tissue plasminogen activator (IV tPA) (intervention arm, 87.1%; control arm, 90.6%) with similar reported times to treatment (intervention arm, 85 minutes; control arm, 87 minutes). Time to groin puncture in the intervention arm was 260 minutes. The mean age of treated patients was 65 years (range, 23e96 years), and newest stent-retriever technology was used in 190 of the 233 patients (81.5%) assigned to IA therapy. General demographics were similar between the 2 groups, with a median National Institutes of Health Stroke Scale score of 17 in the intervention group and 18 in the control group; 25.7% of the patients in the intervention group