Cloft, Harry J.

Objective: Controversy exists as to whether platelet inhibition testing is necessary prior to aneurysm treatment in patients premedicated with antiplatelet agents. Using the IntrePED ( Int ernational Re trospective Study of P ipeline E mbolization D evice) registry, we studied complication rates in platelet-testing and non-platelet testing groups to determine if platelet testing is associated with improved outcomes. Materials and Methods: Patients with unruptured intracranial aneurysms from the INTREPED registry were divided into those who received platelet testing (testing group) and those who did not (nontesting group). Morbidity, mortality and thrombotic and hemorrhagic complication rates were studied. Comparisons between groups for continuous variables were evaluated using t -tests and Fisher’s exact test or Pearson’s chi-square for binary categorical variables. Multivariate logistic regression analysis was performed to determine if platelet function testing was independently associated with poor outcomes adjusting for age, number of devices, aneurysm location, size, and use of multiple exchange wires. Results: When compared to the non-testing group, the platelet testing group suffered higher rates of ipsilateral intracranial hemorrhage (12/511, 2.3% versus 0/187, 0.0%, P=0.04), neurological morbidity (42/511, 8.2% versus 4/187, 2.1%, P=0.01), and combined neurological morbidity and mortality (45/511, 8.8% versus 6/187, 3.2%, P=0.01). More patients in the testing group were treated with multiple PEDs (228 patients, 38.1% versus 57 patients, 28.4%, P=0.01). On multivariate analysis, the platelet testing group had a higher odds of total major morbidity (OR=3.80, 95%CI=1.30=11.08, P=0.01) and total major morbidity and neurological mortality (OR=2.74, 95%CI=1.11-6.79). Conclusion: Our findings caution against blind acceptance of platelet testing in Pipeline patients. Further prospective studies are needed to determine if and when platelet testing in Pipeline patients is appropriate.

Background: Pressure gradients across an intracranial stenosis, or fractional flow (FF), may identify the hemodynamic significance of symptomatic lesions. Computational fluid dynamic (CFD) simulations on 3D morphology of such lesions can calculate these pressure gradients and model effects of systemic physiology interacting with these lesions, such as hypotension and induced hypertension. We studied SAMMPRIS angiography to calculate FF across symptomatic intracranial stenoses and modeled the downstream effect of systemic blood pressure (BP) fluctuations. Methods: Conventional angiography of symptomatic intracranial stenoses in the SAMMPRIS trial was converted from biplanar images to a 3D geometric mesh. CFD simulations were conducted with Ansys CFX on a Cray supercomputer to calculate FF derived from distal/proximal pressure gradients for each of 3 inflow conditions: normal BP (120/80 mm Hg), hypotension (90/60 mm Hg) and hypertension (180/120 mm Hg). Abnormal FF was defined as ≤ 0.8 during diastole to define hemodynamic significance of a stenosis. Results: 407 patients with 70-99% symptomatic stenosis had conventional angiography with biplanar views available for 3D reconstruction in 249, and CFD simulations in 188 (25 VA, 45 BA, 32 ICA, 86 MCA). Under simulated normal inflow conditions (120/80 mm Hg), only 76/188 (40%) cases had low FF. During simulated hypertension, FF improved to normal in 10/188 (5%) cases. Simulated hypotension caused FF to worsen from normal in 12/188 (6%) cases. Other hemodynamic parameters including shear stress could also be calculated and visually depicted in all cases. Conclusions: CFD and hemodynamic modeling of FF can be retrospectively performed after 3D conversion of biplanar angiogram views. FF estimates predict that only 40% of severe (70-99%) symptomatic intracranial stenoses are hemodynamically significant. Systemic BP fluctuations can be modeled during phases of the cardiac cycle to show downstream flow changes.

Background and Purpose- IV rt-PA has become a widely accepted treatment for a select group of patients with acute ischemic stroke. Quantifying the costs of hospitalization is important for understanding the economic impact of these patients on the hospitals that care for them. We evaluated recent data to determine costs associated with hospitalization for acute ischemic stroke patients treated with intravenous thrombolysis, including subgroup analysis to determine the effects of age and discharge status on hospital costs. Methods- Using the National Inpatient Sample, we evaluated the costs for hospitalization for patients treated with intravenous thrombolysis for acute ischemic stroke in the United States from 2001-2008. The primary endpoint examined in this study was total hospital costs, and these were correlated with clinical outcome. Costs were compared with 2008 Medicare reimbursement for intravenous thrombolysis without complication, and intravenous thrombolysis with major complication. Results- A total of 63472 patients received intravenous thrombolysis for acute ischemic stroke. 24094 patients were <65 years old and 40780 patients were ≥65 years old. Median hospital costs in 2008 dollars were $14102 (IQR $9987-$20819) for patients with good outcome, $18856 (IQR $13145-$30423) for patients with severe disability, and $19129 (IQR $11966-$30781) for patients with mortality. Average 2008 Medicare payments were $10,098 for intravenous thrombolysis without complication and $13,835 for intravenous thrombolysis with major complication. Conclusions- Our study of the NIS shows that hospitalization costs in the United States for ischemic stroke patients treated with intravenous thrombolysis are rather high. Medicare payments have not been adequate reimbursement for these hospitalizations. Hopefully, future reconciliation of costs with payments will be feasible, so that hospitals can afford to provide proper care for ischemic stroke patients treated with intravenous thrombolysis.

Background: Severe intracranial atherosclerosis, in excess of 70% luminal stenosis, is an established cause of recurrent stroke. Collateral circulation and the hemodynamic effects of such stenoses, however, may further delineate such risk. We conducted angiographic analyses in the SAMMPRIS trial to correlate the degree of collaterals and hemodynamic effects of such stenoses with baseline clinical and imaging characteristics of enrolled subjects. Methods: Baseline angiography of SAMMPRIS subjects was submitted for blinded review to grade collaterals with the ASITN/SIR scale and antegrade flow across the lesion with TICI. Hemodynamic effect was defined as any flow reduction (a partial TICI score). The association of these angiographic scores (dichotomized as none/partial versus complete collaterals and partial versus complete TICI) and baseline demographic, clinical and imaging variables were evaluated using chi-square tests for percentages and independent group t-tests for means. Results: 424/451 subjects enrolled in SAMMPRIS had baseline angiography available for review, with adequate information to score collaterals in 376 cases. Complete collaterals were noted in 117 (31%). Hemodynamic effects (partial TICI scores) were noted in only 188 (50%) of these lesions, which were all in excess of 70% luminal stenosis. Mean lesion length (n=184, from stenting arm) did not differ between the two categories of either collaterals or hemodynamic impairment. Mean percent stenosis was higher for patients with complete collaterals (none/partial, mean 73.7%; complete, 77.4%; p<0.001) and hemodynamic impairment was more common (p<0.001). More robust collaterals (complete versus none/partial) were associated with patients who at baseline were younger (mean age 58.0 versus 61.5 years; p=0.009), had higher serum HDL (40.0 versus 37.7 mg /dL, p=0.035), participated in moderate exercise (43.1 versus 27.9%, p=0.004) and did not smoke (79.5 versus 69.4%, p=0.042). Previously reported associations with collateral circulation (diabetes, statins, presence of infarction on CT or MRI) were inapparent. These relationships of collaterals with hemodynamic impairment and other baseline variables were established across all anatomical distributions of intracranial stenosis. Conclusions: Severe intracranial atherosclerotic lesions are not always associated with hemodynamic effects. Collateral circulation may also frequently compensate for severe stenosis, with more robust collaterals in younger and healthier individuals.

Background: The degree of collateral circulation is a powerful risk factor for recurrent stroke in the setting of medical therapy for symptomatic intracranial atherosclerosis. The impact of collaterals on the short-term risk for stroke in patients treated by stenting or intensive medical therapies is not known. We systematically evaluated baseline angiographic features of collateral circulation and antegrade flow across intracranial stenoses in randomized subjects of the multicenter SAMMPRIS trial and correlated these to their 30-day risk of ischemic stroke. Methods: Digital review of baseline angiograms in SAMMPRIS was conducted to score ASITN/SIR collateral grade and TICI antegrade flow, blind to other data. Dichotomized collateral and TICI scores (none/partial versus complete) were analyzed independently and in combinations with trial endpoints of territorial ischemic stroke or stroke in territory (SIT) and intracranial hemorrhage (ICH) within 30 days in the intensive medical and stenting arms of the study. Log-rank tests with follow-up time censored at 30 days were used in the analysis. Results: Collaterals could be assessed on 376/424 baseline angiography studies available for digital imaging review for the 451 randomized subjects in SAMMPRIS (186 medical, 190 stenting). Early territorial stroke (SIT) occurred in 6/186 (3.2%) subjects in the medical arm and 20/190 (10.5%) after stenting. SIT was not associated with TICI in either arm, whereas collaterals exerted a potent protective influence in medical (p=0.067) and stented (p=0.004) cases, with 0/66 (0%) SIT in the medical arm and 0/51 (0%) SIT in the stented arm when collaterals were complete. SIT in medical cases was associated with partial TICI/partial collaterals (5/25 (20.0%)) versus complete TICI/partial collaterals (1/95 (1.1%)) and partial TICI/complete collaterals (0/66 (0%)), p<0.001. SIT in stented cases was associated with partial TICI/partial collaterals (11/46 (23.9%)) versus complete TICI/partial collaterals (9/93 (9.7%)) and partial TICI/complete collaterals (0/51 (0%)), p<0.001. ICH within 30 days occurred in 0/186 (0%) subjects randomized to medical therapy. In the stenting arm, early ICH occurred in 8/190 (4.2%) and was associated with TICI (p=0.036) and collaterals (p=0.077). Overall, early ICH after stenting was associated with partial TICI/partial collaterals (7/46 (15.2%)) versus complete TICI/partial collaterals (1/93 (1.1%)) and partial TICI/complete collaterals (0/51 (0%)), p<0.001. Conclusions: Patients with impaired collateral flow associated with severe intracranial stenosis had the highest risk for stroke within 30 days, both with intensive medical therapy and as a complication of angioplasty and stenting.

Introduction: A common risk factor of chronic, nontraumatic subdural hematoma (SDH) is anticoagulation therapy. Anticoagulation is generally held in patients who develop SDH, but this can lead to thromboembolic events. While prior studies have reported the clinical outcomes of patients with anticoagulation-related SDH, there remains little evidence regarding ongoing anticoagulation treatment. Case Report: We report the management of 2 patients who developed anticoagulation-related SDH and underwent middle meningeal artery (MMA) embolization and successful reinitiation of anticoagulation therapy. In both patients, we conservatively managed anticoagulation with heparin and/or enoxaparin as a bridge to warfarin after MMA embolization. Follow-up computed tomography head revealed interval decrease of SDH and stable neurological status. Conclusions: These cases provide anecdotal evidence of a challenging clinical scenario where there is a necessary indication for therapeutic anticoagulation (ie, venous sinus thrombosis or atrial appendage thrombus) and comorbid SDH. Endovascular MMA embolization may be an effective adjunct therapy for clinical scenarios in patients with SDH and an urgent indication for anticoagulation. Longer follow-up, prospective series, and future randomized clinical trials are needed to objectively assess outcomes in this clinically challenging patient population.

OBJECTIVE There is a reported elevated risk of cerebral aneurysms in patients with intracranial dural arteriovenous fistulas (dAVFs). However, the natural history, rate of spontaneous regression, and ideal treatment regimen are not well characterized. In this study, the authors aimed to describe the characteristics of patients with dAVFs and intracranial aneurysms and propose a classification system. METHODS The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database from 12 centers was retrospectively reviewed. Analysis was performed to compare dAVF patients with (dAVF+ cohort) and without (dAVF-only cohort) concomitant aneurysm. Aneurysms were categorized based on location as a dAVF flow-related aneurysm (FRA) or a dAVF non–flow-related aneurysm (NFRA), with further classification as extra- or intradural. Patients with traumatic pseudoaneurysms or aneurysms with associated arteriovenous malformations were excluded from the analysis. Patient demographics, dAVF anatomical information, aneurysm information, and follow-up data were collected. RESULTS Of the 1077 patients, 1043 were eligible for inclusion, comprising 978 (93.8%) and 65 (6.2%) in the dAVF-only and dAVF+ cohorts, respectively. There were 96 aneurysms in the dAVF+ cohort; 10 patients (1%) harbored 12 FRAs, and 55 patients (5.3%) harbored 84 NFRAs. Dural AVF+ patients had higher rates of smoking (59.3% vs 35.2%, p < 0.001) and illicit drug use (5.8% vs 1.5%, p = 0.02). Sixteen dAVF+ patients (24.6%) presented with aneurysm rupture, which represented 16.7% of the total aneurysms. One patient (1.5%) had aneurysm rupture during follow-up. Patients with dAVF+ were more likely to have a dAVF located in nonconventional locations, less likely to have arterial supply to the dAVF from external carotid artery branches, and more likely to have supply from pial branches. Rates of cortical venous drainage and Borden type distributions were comparable between cohorts. A minority (12.5%) of aneurysms were FRAs. The majority of the aneurysms underwent treatment via either endovascular (36.5%) or microsurgical (15.6%) technique. A small proportion of aneurysms managed conservatively either with or without dAVF treatment spontaneously regressed (6.2%). CONCLUSIONS Patients with dAVF have a similar risk of harboring a concomitant intracranial aneurysm unrelated to the dAVF (5.3%) compared with the general population (approximately 2%–5%) and a rare risk (0.9%) of harboring an FRA. Only 50% of FRAs are intradural. Dural AVF+ patients have differences in dAVF angioarchitecture. A subset of dAVF+ patients harbor FRAs that may regress after dAVF treatment.

Background and Purpose: We performed a systematic review and meta-analysis comparing rates of recanalization, good neurological outcome, and mortality between patients treated with three modern devices used for endovascular treatment of acute ischemic stroke. Materials and Methods: We performed a comprehensive literature search on studies reporting outcomes of endovascular treatment of acute ischemic stroke. We selected studies including≥30 patients treated with either the Trevo stent-retriever, Penumbra aspiration system or the Solitaire stent-retriever. Outcomes studied included mrs≤2, 90-day mortality, symptomatic and intracranial hemorrhage (sICH), recanalization. Outcomes were pooled across studies using a random-effects meta-analysis. Results: 27 articles with 2666 patients were included (1514 Solitaire, 260 Trevo and 892 Penumbra). Rates of good neurological outcome (mRS≤2) were higher in the Solitaire group (54.0%, 95%CI=49.0-58.0%) than the Penumbra group (39.0%, 95%CI=31.0%-47.0%) (P<0.01). There was a trend towards higher rates of good neurological outcome in the Solitaire compared to the Trevo group (P=0.08). Rates of 90-day mortality were significantly lower in the Solitaire group (16.0%, 95%CI=11.0%-22.0%) than in the Penumbra group (27.0%, 95%CI=24.0%-30.0%) (P<0.01) and the Trevo group (23.0%, 95%CI=13.0-33.0)(P=0.01). Recanalization rates were similar between groups at 80.0% (95%CI=75.0%-84.0% for the Solitaire group, 82.0% (95%CI=75.0%-88.0%) for the Penumbra group (P=0.54) and 76.0% (95%CI=68.0-83.0) for the Trevo group (P=0.13 vs Penumbra and P=0.27 vs. Solitaire). Conclusions: Meta-analysis of incidence rates in noncomparative series reporting on over 2500 patients suggests that the Solitaire device maybe associated with superior neurological outcomes and lower rates of 90-day mortality. Comparative studies are needed to confirm these observations.

Introduction: Five randomized trials proving the efficacy and safety of mechanical embolectomy for ischemic stroke patients used differing radiological methods to select patients for treatment. Hypothesis: The percentage of patients evaluated in a non-clinical trial setting that would meet radiological criteria to be included in the five trials will differ substantially. Methods: Retrospective study of consecutive ischemic stroke patients who were considered for endovascular stroke therapy based on confirmed intracranial large vessel occlusion (M1, M2, or carotid terminus) at an academic medical center from April 2010 - November 2014. All patients underwent CT perfusion and CT angiogram. Results: The table shows baseline characteristics of 119 patients. Median age was 69 years (IQR 57-79) and median NIHSS 18 (IQR 14-21). Most patients had ASPECTS score ≥ 6 (n=105, 88.2%). The M1 segment of MCA was the most common vessel occluded (n=81, 68%). All 119 patients (100%) met radiological criteria for MR CLEAN while 105 (88.2%) met criteria for SWIFT-PRIME, 96 (80.7%) for REVASCAT, 80/116 (69.0%) for EXTEND IA, and 74 (62.2%) for ESCAPE. IV TPA was given to 58 patients (48.7%) and acute endovascular stroke therapy attempted in 66 (55.5%). Any intracranial hemorrhage was more common in the patients treated with endovascular therapy than in those who were not (36% vs. 17%, p=0.025). The frequency of symptomatic ICH did not significantly differ between these two groups (6.1% vs 3.8%, p=0.691). Conclusions: The percentage of patients with acute stroke and large vessel occlusion that would qualify for endovascular stroke trials based on radiological criteria varies considerably (62%-100%) in a non-clinical trial cohort from an academic comprehensive stroke center. Additional individual patient characteristics influence treatment decisions in non-clinical trial settings.