Kallmes, David F.

Background Patients with an acute ischemic stroke (AIS) due to large vessel occlusion often require transfer to an endovascular center for treatment. Objective To assess the effect of hospital transfer on outcomes after endovascular revascularization. Methods Outcomes of endovascular revascularization were compared between directly admitted and transferred patients using data from a national database and our own institution. Results 118 institutions within the database reported outcomes of 8533 inpatient admissions for endovascular treatment of AIS. Mortality rate (14.9% vs 18.6%; p=0.049) and mortality index (1.1 vs 1.6; p=0.048) were significantly lower among directly admitted patients than among transferred patients. Within our institutional cohort of 140 patients who underwent endovascular therapy, directly admitted patients had a significantly faster time to revascularization than transferred patients (277.4 vs 420.4 min; p≤0.0001). Among transferred patients, an increasing distance of transferred hospital to our home institution was associated with an increasing risk of mortality (unit OR=1.26, 95% CI 1.07 to 1.54; p=0.0061). Conclusions Outcomes of revascularization may improve with methods to identify patients with large vessel occlusion before hospital admission, thus increasing the likelihood of initial triage to a comprehensive stroke center for patients eligible for endovascular intervention.

Background Many CT angiography (CTA) collateral scoring systems are either subjective or complex and time consuming. Objective To evaluate the correlation between a CTA collateral scoring system—the Opercular Index Score (OIS)—with neurological outcomes at 90 days following endovascular treatment for acute ischemic stroke (AIS) secondary to large vessel occlusion. Methods Fifty-five patients with AIS due to distal internal carotid artery, M1, or proximal M2 occlusions who underwent endovascular treatment were included. OIS was retrospectively calculated from CTA images, reconstructed from CT perfusion imaging, as the ratio of opacified M3 opercular branches in the Sylvian fissure on the unaffected side to those on the stroke side and dichotomized into favorable (OIS≤2) and poor (OIS>2). The ability of OIS to predict good neurological outcomes (modified Rankin Scale score ≤2 at 90 days) was assessed using sensitivity, specificity, and area under the curve (AUC) with receiver operating characteristic analysis. Results Thirty-five patients had a favorable OIS and 20 patients had a poor OIS. Patients with favorable OIS had an 80.0% (n=28) rate of good neurological outcomes compared with 15.0% (n=3) of patients with a poor OIS (p<0.0001). On multivariate logistic regression analysis adjusting for baseline National Institutes of Health Stroke Scale score, OIS, and device used, favorable OIS was the only variable independently associated with good neurological outcome (OR=17.2, 95% CI 3.8 to 104.3) and demonstrated a sensitivity of 90.3% and specificity of 70.8% with an AUC of 0.822. Conclusions OIS is a simple and practical non-invasive scoring system that can be used to predict collateral robustness and good neurological outcome among patients with AIS undergoing endovascular treatment.

OBJECTIVEThe authors performed a pooled analysis of 3 studies—IntrePED (International Retrospective Study of the Pipeline Embolization Device), PUFS (Pipeline for Uncoilable or Failed Aneurysms Study), and ASPIRe (Aneurysm Study of Pipeline in an Observational Registry)—in order to assess angiographic outcomes and clinical safety of the Pipeline embolization device (PED).METHODSIntrePED was a retrospective study, while PUFS and ASPIRe were prospective studies. For each patient included in these studies, the authors collected baseline demographic data, aneurysm characteristics, and procedural details. The primary outcomes for this combined analysis were clinical outcomes, including neurological morbidity and mortality and major ipsilateral intracranial hemorrhage and ischemic stroke. The secondary outcomes were angiographic occlusion rates, which were available for ASPIRe and PUFS only.RESULTSA total of 1092 patients with 1221 aneurysms were included across the 3 studies. The mean aneurysm size was 12.0 ± 7.8 mm and the mean neck size was 6.6 ± 4.8 mm. The major ipsilateral ischemic stroke rate was 3.7% (40/1091). The major ipsilateral intracranial hemorrhage rate was 2.0% (22/1091). The major neurological morbidity rate was 5.7% (62/1091). The neurological mortality rate was 3.3% (36/1091). The combined major morbidity and neurological mortality rate was 7.1% (78/1091). The complete occlusion rates were 75.0% at 180 days (111/148) and 85.5% at 1 year (94/110). The overall aneurysm retreatment rate was 3.0% (33/1091) at a mean follow-up time of 10.2 ± 10.8 months.CONCLUSIONSEndovascular treatment of intracranial aneurysms with the PED is safe and effective. Angiographic occlusion rates progressed with follow-up. Rates of stroke, hemorrhage, morbidity and mortality, and retreatment were low, especially given the fact that the aneurysms treated were generally large and wide necked.

OBJECTIVEThe long-term effectiveness of endovascular treatment of large and giant wide-neck aneurysms using traditional endovascular techniques has been disappointing, with high recanalization and re-treatment rates. Flow diversion with the Pipeline Embolization Device (PED) has been recently used as a stand-alone therapy for complex aneurysms, showing significant improvement in effectiveness while demonstrating a similar safety profile to stent-supported coil treatment. However, relatively little is known about its long-term safety and effectiveness. Here the authors report on the 3-year safety and effectiveness of flow diversion with the PED in a prospective cohort of patients with large and giant internal carotid artery aneurysms enrolled in the Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial.METHODSThe PUFS trial is a prospective study of 107 patients with 109 aneurysms treated with the PED. Primary effectiveness and safety end points were demonstrated based on independently monitored 180-day clinical and angiographic data. Patients were enrolled in a long-term follow-up protocol including 1-, 3-, and 5-year clinical and imaging follow-up. In this paper, the authors report the midstudy (3-year) effectiveness and safety data.RESULTSAt 3 years posttreatment, 74 subjects with 76 aneurysms underwent catheter angiography as required per protocol. Overall, complete angiographic aneurysm occlusion was observed in 71 of these 76 aneurysms (93.4% cure rate). Five aneurysms were re-treated, using either coils or additional PEDs, for failure to occlude, and 3 of these 5 were cured by the 3-year follow-up. Angiographic cure with one or two treatments of Pipeline embolization alone was therefore achieved in 92.1%. No recanalization of a previously completely occluded aneurysm was noted on the 3-year angiograms. There were 3 (2.6%) delayed device- or aneurysm-related serious adverse events, none of which led to permanent neurological sequelae. No major or minor late-onset hemorrhagic or ischemic cerebrovascular events or neurological deaths were observed in the 6-month through 3-year posttreatment period. Among 103 surviving patients, 85 underwent functional outcome assessment in which modified Rankin Scale scores of 0–1 were demonstrated in 80 subjects.CONCLUSIONSPipeline embolization is safe and effective in the treatment of complex large and giant aneurysms of the intracranial internal carotid artery. Unlike more traditional endovascular treatments, flow diversion results in progressive vascular remodeling that leads to complete aneurysm obliteration over longer-term follow-up without delayed aneurysm recanalization and/or growth.Clinical trial registration no.: NCT00777088 (clinicaltrials.gov)

Patients with connective tissue diseases are thought to be at a higher risk for a number of cerebrovascular diseases such as intracranial aneurysms, dissections, and acute ischemic strokes. In this report, we aim to understand the prevalence and occurrences of such neurovascular manifestations in four heritable connective tissue disorders: Marfan syndrome, Ehlers-Danlos syndrome, Neurofibromatosis Type 1, and Loeys-Dietz syndrome. We discuss the fact that although there are various case studies reporting neurovascular findings in these connective tissue diseases, there is a general lack of case-control and prospective studies investigating the true prevalence of these findings in these patient populations. Furthermore, the differences observed in the manifestations and histology of such disease pathologies encourages future multi-center registries and studies in better characterizing the pathophysiology, prevalence, and ideal treatment options of neurovascular lesions in patents with connective tissue diseases.

Background Prior research on the efficacy of vertebroplasty has focused primarily on subjective, patient-reported outcomes. Objective To apply an armband activity monitor (SenseWear by BodyMedia Inc, USA) to patients presenting for consideration for vertebroplasty and to determine the correlation between patient-reported outcomes and quantitative activity metrics at baseline and 30 days after presentation. Materials and methods Nineteen patients were enrolled (15 receiving vertebroplasty, 4 not receiving vertebroplasty). Patients reported their average pain over the past 24 hours and completed the Roland–Morris disability questionnaire at baseline and 30 days. Patients wore the SenseWear Armband activity monitor for a median of 4 days at baseline and at the 30-day time period to assess steps, metabolic equivalents expended, sedentary activity time, moderate activity time, sleep efficiency, and total sleep time. Pain and disability scores were correlated with activity monitor metrics using linear regression analysis. Results Changes in reported average pain in the past 24 hours and disability scores were not significantly different between vertebroplasty and non-vertebroplasty groups (p>0.05). Changes in activity monitor data were not significantly different between the vertebroplasty and non-vertebroplasty groups (p>0.05). None of the correlations between the reported pain or disability scores and the activity monitor data were significant. Conclusions Activity monitors can be used to objectively record changes in activity following vertebroplasty procedures. Patient-reported pain or disability scores do not correlate with activity monitor-measured activity or sleep metrics.

Abstract Rationale There is sparse published literature on the causes and outcomes of hospitalization of patients with hereditary hemorrhagic telangiectasia (HHT). Objectives To evaluate rates of various complications, comorbidities, and in-hospital outcomes of patients with HHT using a large, multihospital inpatient database. Methods We identified patients with HHT in the U.S. Nationwide Inpatient Sample between 2000 and 2012. Rates of hemorrhagic, neurological, hepatic, and cardiopulmonary complications among hospitalized patients with HHT were evaluated. We also studied procedure use rates for blood transfusion, endoscopy, and epistaxis treatment. Hospitalization outcomes, including in-hospital mortality, discharge status, charges, and length of stay, were evaluated. Measurements and Main Results: We identified 10,293 patients with HHT. The mean age of the HHT population was 60.7 years. Sixty percent of patients were female. More than 75% of HHT hospitalizations occurred in those older than 50 years of age. Patients with HHT had high rates of bleeding-related complications, including anemia (53.3%), epistaxis (16.2%), and gastrointestinal bleeding (10.8%). Overall, bleeding complications accounted for 62.7% of HHT-related complications. Thirty-eight percent of hospitalized patients with HHT received one or more transfusions of a blood product. Cardiopulmonary complications were present in 41.0% of the cases. Congestive heart failure was the second most common individual complication among patients with HHT, affecting 19.9% of patients. The in-hospital mortality rate was 1.9%. Conclusions In this large, nationwide study, we found that nearly two-thirds of patients hospitalized with HHT experienced a bleeding-related complication. Nearly 40% of hospitalized patients with HHT required transfusion of blood products. Cardiopulmonary complications, including congestive heart failure, were the second most common complication. The high burden of bleeding-related complications points to a significant unmet clinical need for these patients.

Objective To assess the feasibility of using MicroFil polymer perfusion to detect concomitant saccular aneurysms in an intracranial arterial dolichoectasia (IADE) model in mice, and to report detailed histomorphometric features of these aneurysms. Materials and methods IADE models were created in C57/BL6 mice via microsurgical injection of 25 mU elastase into the cisterna magna. The cerebral vasculature was perfused with MicroFil polymer and harvested at 1, 3, and 7 days, and 2 and 4 weeks (n=8 for each group). IADE was defined by a tortuosity index >10 combined with a 25% increase in diameter of the A1 segment of the anterior cerebral artery (ACA), internal carotid artery (ICA), or basilar artery compared with the baseline of controls, which received heat-inactivated elastase. Saccular aneurysm occurrence rate, location, and morphological parameters were investigated using macroscopic and microscopic analysis. Results IADE was present in 95% (36/38) of the subjects, with a mortality rate of 5% (2/40). Fifteen concomitant saccular aneurysms were detected in 8 (21%) of the 38 surviving mice, including 6 at the posterior communicating artery, 1 along the ACA, 2 along the anterior communicating artery complex, 3 along the ICA, and 3 along the middle cerebral artery. Rupture was confirmed in two aneurysms. Histological examination indicated that the aneurysms develop via arterial-wall remodelling, which is characterized by internal elastic lamina disruptions and muscular layer discontinuity in the media. Conclusions The proportion of subjects developing saccular aneurysms in addition to IADE in our mouse model is similar to the 15% of patients with IADE who have concomitant saccular aneurysms.