Predictors of acute post-thrombectomy intracranial hemorrhage expansion in anterior circulation infarcts.

BACKGROUND: Post-mechanical thrombectomy (MT) intracranial hemorrhage (ICH) is a major source of morbidity in treated acute ischemic stroke patients with large vessel occlusion. ICH expansion may further contribute to morbidity. We sought to identify factors associated with ICH expansion on imaging evaluation post-MT. METHODS: We performed a retrospective cohort study of patients undergoing MT at a single comprehensive stroke center. Per protocol, patients underwent dual-energy head CT (DEHCT) post-MT followed by a 24-h interval non-contrast enhanced MRI. ICH expansion was defined as any increase in blood volume between the two studies if identified on the DEHCT. Univariate and multivariable analyses were performed to identify risk factors for ICH expansion. RESULTS: ICH was identified on DEHCT in 13% of patients (n = 35/262), with 20% (7/35) demonstrating expansion on interval MRI. The average increase in blood volume was 11.4 ml (SD 6.9). Univariate analysis identified anticoagulant usage (57% vs 14%, p = 0.03), petechial hemorrhage inside the infarct margins or intraparenchymal hematoma on DEHCT (ECASS-II HI2/PH1/PH2) (71% vs 14%, p < 0.01), basal ganglia hemorrhage (71% vs 21%, p = 0.02), and basal ganglia infarction (86% vs 32%, p = 0.03) as factors associated with ICH expansion. Multivariate regression demonstrated that anticoagulant usage (OR 20.3, 95% C.I. 2.43-446, p < 0.05) and ECASS II scores of HI2/PH1/PH2 (OR 11.7, 95% C.I. 1.24-264, p < 0.05) were significantly predictive of ICH expansion. CONCLUSION: Expansion of post-MT ICH on 24-h interval MRI relative to immediate post-thrombectomy DEHCT is significantly associated with baseline anticoagulant usage and petechial hemorrhage inside the infarct margins or presence of intraparenchymal hematoma (ECASS-II HI2/PH1/PH2).

Low Levels of Low-Density Lipoprotein Cholesterol Increase the Risk of Post-Thrombectomy Delayed Parenchymal Hematoma.

PURPOSE: Low levels of low-density lipoprotein cholesterol (LDL-C) have been suggested to increase the risk of hemorrhagic transformation (HT) following acute ischemic stroke. However, the literature on the relationship between LDL-C levels and post-thrombectomy HT is sparse. The aim of our study is to investigate the association between LDL-C and delayed parenchymal hematoma (PH) that was not seen on immediate post-thrombectomy dual-energy computed tomography (DECT). MATERIALS AND METHODS: A retrospective analysis was conducted on all patients with anterior circulation large vessel occlusion who underwent thrombectomy at a comprehensive stroke center from 2018-2021. Per institutional protocol, all patients received DECT immediately post-thrombectomy and magnetic resonance imaging or CT at 24 hours. The presence of immediate hemorrhage was assessed by DECT, while delayed PH was assessed by 24-hour imaging. Multivariable analysis was performed to identify predictors of delayed PH. Patients with hemorrhage on immediate post-thrombectomy DECT were excluded to select only those with delayed PH. RESULTS: Of 159 patients without hemorrhage on immediate post-thrombectomy DECT, 18 (11%) developed delayed PH on 24-hour imaging. In multivariable analysis, LDL-C (odds ratio [OR], 0.76; P=0.038; 95% confidence interval [CI], 0.59-0.99; per 10 mg/dL increase) independently predicted delayed PH. High-density lipoprotein cholesterol, triglyceride, and statin use were not associated. After adjusting for potential confounders, LDL-C ≤50 mg/dL was associated with an increased risk of delayed PH (OR, 5.38; P=0.004; 95% CI, 1.70-17.04), while LDL-C >100 mg/dL was protective (OR, 0.26; P=0.041; 95% CI, 0.07-0.96). CONCLUSION: LDL-C ≤50 mg/dL independently predicted delayed PH following thrombectomy and LDL-C >100 mg/dL was protective, irrespective of statin. Thus, patients with low LDL-C levels may warrant vigilant monitoring and necessary interventions, such as blood pressure control or anticoagulation management, following thrombectomy even in the absence of hemorrhage on immediate post-thrombectomy DECT.

The clinical utility of dual-energy CT in post-thrombectomy care: Part 2, the predictive value of contrast density and volume for delayed hemorrhagic transformation.

OBJECTIVES: Dual-energy CT allows differentiation between blood and iodinated contrast. This study aims to determine the predictive value of contrast density and volume on post-thrombectomy dual-energy CT for delayed hemorrhagic transformation and its impact on 90-day outcomes. MATERIALS AND METHODS: A retrospective analysis was performed on patients who underwent thrombectomy for anterior circulation large-vessel occlusion at a comprehensive stroke center from 2018-2021. Per institutional protocol, all patients underwent dual-energy CT immediately post-thrombectomy and MRI or CT 24 hours afterward. The presence of hemorrhage and contrast staining was evaluated by dual-energy CT. Delayed hemorrhagic transformation was determined by 24-hour imaging and classified into petechial hemorrhage or parenchymal hematoma using ECASS III criteria. Univariable and multivariable analyses were performed to determine predictors and outcomes of delayed hemorrhagic transformation. RESULTS: Of 97 patients with contrast staining and without hemorrhage on dual-energy CT, 30 and 18 patients developed delayed petechial hemorrhage and delayed parenchymal hematoma, respectively. On multivariable analysis, delayed petechial hemorrhage was predicted by anticoagulant use (OR,3.53;p=0.021;95%CI,1.19-10.48) and maximum contrast density (OR,1.21;p=0.004;95%CI,1.06-1.37;per 10 HU increase), while delayed parenchymal hematoma was predicted by contrast volume (OR,1.37;p=0.023;95%CI,1.04-1.82;per 10 mL increase) and low-density lipoprotein (OR,0.97;p=0.043;95%CI,0.94-1.00;per 1 mg/dL increase). After adjusting for potential confounders, delayed parenchymal hematoma was associated with worse functional outcomes (OR,0.07;p=0.013;95%CI,0.01-0.58) and mortality (OR,7.83;p=0.008;95%CI,1.66-37.07), while delayed petechial hemorrhage was associated with neither. CONCLUSION: Contrast volume predicted delayed parenchymal hematoma, which was associated with worse functional outcomes and mortality. Contrast volume can serve as a useful predictor of delayed parenchymal hematoma following thrombectomy and may have implications for patient management.

The clinical utility of dual-energy CT in post-thrombectomy care: Part 1, predictors and outcomes of subarachnoid and intraparenchymal hemorrhage.

OBJECTIVES: Dual-energy CT allows differentiation between blood and iodinated contrast. We aimed to determine predictors of subarachnoid and intraparenchymal hemorrhage on dual-energy CT performed immediately post-thrombectomy and the impact of these hemorrhages on 90-day outcomes. MATERIALS AND METHODS: A retrospective analysis was performed on patients who underwent thrombectomy for anterior circulation large-vessel occlusion and subsequent dual-energy CT at a comprehensive stroke center from 2018-2021. The presence of contrast, subarachnoid hemorrhage, or intraparenchymal hemorrhage immediately post-thrombectomy was assessed by dual-energy CT. Univariable and multivariable analyses were performed to identify predictors of post-thrombectomy hemorrhages and 90-day outcomes. Patients with unknown 90-day mRS were excluded. RESULTS: Of 196 patients, subarachnoid hemorrhage was seen in 17, and intraparenchymal hemorrhage in 23 on dual-energy CT performed immediately post-thrombectomy. On multivariable analysis, subarachnoid hemorrhage was predicted by stent retriever use in the M2 segment of MCA (OR,4.64;p=0.017;95%CI,1.49-14.35) and the number of thrombectomy passes (OR,1.79;p=0.019;95%CI,1.09-2.94;per an additional pass), while intraparenchymal hemorrhage was predicted by preprocedural non-contrast CT-based ASPECTS (OR,8.66;p=0.049;95%CI,0.92-81.55;per 1 score decrease) and preprocedural systolic blood pressure (OR,5.10;p=0.037;95%CI,1.04-24.93;per 10 mmHg increase). After adjusting for potential confounders, intraparenchymal hemorrhage was associated with worse functional outcomes (OR,0.25;p=0.021;95%CI,0.07-0.82) and mortality (OR,4.30;p=0.023,95%CI,1.20-15.36), while subarachnoid hemorrhage was associated with neither. CONCLUSIONS: Intraparenchymal hemorrhage immediately post-thrombectomy was associated with worse functional outcomes and mortality and can be predicted by low ASPECTS and elevated preprocedural systolic blood pressure. Future studies focusing on management strategies for patients presenting with low ASPECTS or elevated blood pressure to prevent post-thrombectomy intraparenchymal hemorrhage are warranted.

Oral health and functional outcomes following mechanical thrombectomy for ischemic stroke.

BACKGROUND: An association between poor dentition and the risk of ischemic stroke has previously been reported in the literature. In this study we assessed oral hygiene (OH), including tooth loss and the presence of dental disease, to determine if an association exists with functional outcomes following mechanical thrombectomy (MT) for large-vessel ischemic stroke. METHODS: A retrospective review was conducted of consecutive adult patients at a single comprehensive stroke center who underwent MT from 2012 to 2018. Inclusion criteria included availability of CT imaging to radiographically assess OH. A multivariate analysis was performed, with the primary outcome being 90-day post-thrombectomy modified Rankin Scale (mRS) score >2. RESULTS: A total of 276 patients met the inclusion criteria. The average number of missing teeth was significantly higher in patients with a poor functional outcome (mean (SD) 10 (11) vs 4 (6), p<0.001). The presence of dental disease was associated with poor functional outcome, including cavities (21 (27%) vs 13 (8%), p<0.001), periapical infection (18 (23%) vs 11 (6.7%), p<0.001), and bone loss (27 (35%) vs 11 (6.7%), p<0.001). Unadjusted, missing teeth was a univariate predictor of poor outcome (OR 1.09 (95% CI 1.06 to 1.13), p<0.001). After adjustment for recanalization scores and use of tissue plasminogen activator (tPA), missing teeth remained a predictor of poor outcome (OR 1.07 (95% CI 1.03 to 1.11), p<0.001). CONCLUSION: Missing teeth and the presence of dental disease are inversely correlated with functional independence following MT, independent of thrombectomy success or tPA status.

Saline versus Balanced Crystalloids for Adults with Aneurysmal Subarachnoid Hemorrhage: A Subgroup Analysis of the SMART Trial.

Background: Whether the composition of intravenous crystalloid solutions affects outcomes in adults with aneurysmal subarachnoid hemorrhage (aSAH) remains unknown. Therefore, we determined whether the use of saline is associated with lower risk of disability and death in aSAH patients compared to balanced crystalloids. Methods: We conducted a post hoc subgroup analysis of the Isotonic Solutions and Major Adverse Renal Events Trial (SMART), a pragmatic, unblinded, cluster-randomized, multiple-crossover clinical trial that enrolled 15,802 adults between June 2015 and April 2017. We compared intravenous administration of saline to balanced crystalloids in consecutively enrolled aSAH patients aged 18 years or older whose ruptured aneurysm was procedurally secured at a single academic center in the United States. The primary outcome was the score on the modified Rankin scale (mRS, range, 0 [no symptoms] to 6 [death]) at 90 days obtained from a prospective institutional stroke registry. Secondary outcome included death by 90 days. Logistic or proportional odds regression models were used to test for between-group differences adjusted for age, hypertension, aSAH grade, and procedure type. Results: Of the 79 aSAH patients procedurally treated during the SMART study period, 78 were enrolled (median age, 58 years; IQR, 49 to 64.5; 64% female), with 41 (53%) assigned to saline and 37 (47%) to balanced crystalloids. Plasma-Lyte was the primary balanced crystalloid used. Among 72 patients with 90-day mRS assessment, the adjusted common odds ratio, aOR, for mRS was 0.68 (95% CI, 0.28-1.63; P=0.39), with values less than 1.0 favoring saline. By 90 days, 2/39 patients (5%) in the saline group and 9/35 (26%) in the balanced-crystalloids group had died (aOR, 0.06; 95% CI, 0.00-0.50; P=0.02). Conclusions: Among procedurally treated aSAH patients, the risk of disability or death at 90 days did not significantly differ between saline and balanced crystalloids. Death occurred less frequently with saline than balanced crystalloids.

Impact of neurovascular comorbidities and complications on outcomes after procedural management of arteriovenous malformations.

OBJECTIVE: Cerebral arteriovenous malformations (AVMs) are complex vascular lesions at perpetual risk for rupture, which can lead to significant morbidity and mortality. This study sought to evaluate the dynamic relationship between comorbidities and post-procedure complications to quantify the risk of poor discharge outcomes to create a predictive outcomes model. METHODS: The National Inpatient Sample (NIS) data from 2012 to 2015 was queried for AVM treatment using International Classification of Diseases, Ninth Revision codes. The Neurovascular Comorbidities Index (NCI) quantified patient comorbidity burden. In-hospital complications included surgical and medical complications or seizures. The primary outcome was the NIS Subarachnoid Hemorrhage Outcome Measure (NIS-SOM). RESULTS: A total of 1363 patients were included. A total of 1330 patients (98%) underwent embolization, 28 (2%) underwent resection, and 9 (0.7%) underwent radiosurgery. A higher NCI was associated with the occurrence of any complication (odds ratio [OR], 1.30 if NCI = 2; P < 0.001). Higher NCI was also significantly associated with a poor NIS-SOM outcome (OR, 2.45 if NCI = 2 and no complications; P < 0.001). A ruptured AVM with intracranial hemorrhage (ICH) increased the risk of in-hospital complications (OR, 2.16; P = 0.007) and a poor NIS-SOM outcome (OR, 3.18; P < 0.001). Various hypothetical patient scenarios and the predicted outcomes are also presented. CONCLUSION: Neurovascular comorbidities have a significant impact on poor functional outcomes at discharge in patients with and without complications following procedural management of AVMs. At the time of initial patient assessment, risk stratification strategies should take into account neurovascular comorbidities and potential complications. Such an approach would ultimately optimize patient outcomes and increase the value of care provided.

Conditional Vasospasm-Free Survival Following Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Following aneurysmal subarachnoid hemorrhage (SAH), patients are monitored closely for vasospasm in the intensive care unit. Conditional vasospasm-free survival describes the risk of future vasospasm as a function of time elapsed without vasospasm. Conditional survival has not been applied to this clinical scenario but could improve patient counseling and intensive care unit use. The objective of this study was to characterize conditional vasospasm-free survival following SAH. METHODS: This was a single institution, retrospective cohort study of patients treated for aneurysmal SAH between 1/1/2000-6/1/2020. The primary outcome was the development of vasospasm defined by the first instance of either radiographic vasospasm on computed tomography angiography, Lindegaard Index > 3.0 by transcranial doppler ultrasonography, or vasospasm-specific intraarterial therapy. Multivariable Cox regression was performed, and conditional vasospasm-free survival curves were constructed. RESULTS: A total of 528 patients were treated for aneurysmal SAH and 309 (58.5%) developed vasospasm. Conditional survival curves suggest patients who survive to postbleed day 10 without vasospasm have a nearly 90% chance of being discharged without vasospasm. The median onset of vasospasm was postbleed day 6. Age more than 50 years was associated with a lower risk (hazard ratio [HR] = .76; 95% confidence interval [CI] 0.64-0.91; p < 0.001). Higher initial systolic blood pressure (HR = 1.18; 95% CI 1.046-1.350; p = .008), Hunt-Hess grades 4 or 5 (HR = 1.304; 95% CI 1.014-1.676), and modified Fisher scale score of 4 (HR = 1.808; 95% CI 1.198-2.728) were associated with higher vasospasm than the respective lower grades. CONCLUSION: Conditional survival provides a useful framework for counseling patients and making decisions around vasospasm risk for patients with aneurysmal SAH, while risk factor-stratified plots facilitate a patient-centric, evidence-based approach to these conversations and decisions.

CYP2C19 Loss-of-Function Associated with First-Time Ischemic Stroke in Non-surgical Asymptomatic Carotid Artery Stenosis During Clopidogrel Therapy.

This study measures effect of CYP2C19 genotype on ischemic stroke risk during clopidogrel therapy for asymptomatic, extracranial carotid stenosis patients. Using deidentified electronic health records, patients were selected for retrospective cohort using administrative code for carotid stenosis, availability of CYP2C19 genotype result, clopidogrel exposure, and established patient care. Patients with intracranial atherosclerosis, aneurysm, arteriovenous malformation, prior ischemic stroke, or observation time <1 month were excluded. Dual antiplatelet therapy patients were included. Patients with carotid endarterectomy or stenting were analyzed in a separate subgroup. Time-to-event analysis using Cox regression was conducted to model ischemic stroke events based on CYP2C19 loss-of-function allele and adjusted with the most predictive covariates from univariate analysis. Covariates included age, gender, race, length of aspirin, length of concurrent antiplatelet/anticoagulant treatment, diabetes, coagulopathy, hypertension, heart disease, atrial fibrillation, and lipid disorder. A total of 1110 patients met selection criteria for medical therapy cohort (median age 68 [interquartile range (IQR) 60-75] years, 64.9% male, 91.9% Caucasian). Median study period was 2.8 [0.8-5.3] years. A total of 47 patients (4.2%) had an ischemic stroke event during study period. CYP2C19 loss-of-function allele was strongly associated with ischemic stroke events (one allele: HR 2.3, 95% CI 1.1-4.7, p=0.020; two alleles: HR 10.2, 95% CI 2.8-36.8, p<0.001) after adjustment. For asymptomatic carotid stenosis patients receiving clopidogrel to prevent ischemic stroke, CYP2C19 loss-of-function allele is associated with 2- to 10-fold increased risk of ischemic stroke. CYP2C19 genotype may be considered when selecting antiplatelet therapy for stroke prophylaxis in non-procedural, asymptomatic carotid stenosis.

Creation and Validation of a Stroke Scale to Increase Utility of National Inpatient Sample Administrative Data for Clinical Stroke Research.

INTRODUCTION: The National Inpatient Sample (NIS) has led to several breakthroughs via large sample size. However, utility of NIS is limited by the lack of admission NIHSS and 90-day modified Rankin score (mRS). This study creates estimates for stroke severity at admission and 90-day mRS using NIS data for acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT). METHODS: Three patient cohorts undergoing MT for AIS were utilized: Cohort 1 (N = 3729) and Cohort 3 (N = 1642) were derived from NIS data. Cohort 2 (N=293) was derived from a prospectively-maintained clinical registry. Using Cohort 1, Administrative Stroke Outcome Variable (ASOV) was created using disposition and mortality. Factors reflective of stroke severity were entered into a stepwise logistic regression predicting poor ASOV. Odds ratios were used to create the Administrative Data Stroke Scale (ADSS). Performances of ADSS and ASOV were tested using Cohort 2 and compared with admission NIHSS and 90-day mRS, respectively. ADSS performance was compared with All Patient Refined-Diagnosis Related Group (APR-DRG) severity score using Cohort 3. RESULTS: Agreement of ASOV with 90-day mRS > 2 was fair (κ = 0.473). Agreement with 90-day mRS > 3 was substantial (κ = 0.687). ADSS significantly correlated (p < 0.001) with clinically-significant admission NIHSS > 15. ADSS performed comparably (AUC = 0.749) to admission NIHSS (AUC = 0.697) in predicting 90-day mRS > 2 and mRS > 3 (AUC = 0.767, 0.685, respectively). ADSS outperformed APR-DRG severity score in predicting poor ASOV (AUC = 0.698, 0.682, respectively). CONCLUSION: We developed and validated measures of stroke severity at admission (ADSS) and outcome (ASOV, estimate for 90-day mRS > 3) to increase utility of NIS data in stroke research.

Association of asymptomatic hemorrhage after endovascular stroke treatment with outcomes.

BACKGROUND: Intracerebral hemorrhage (ICH) occurs in ~20%-30% of stroke patients undergoing endovascular therapy (EVT). However, there is conflicting evidence regarding the effect of asymptomatic ICH (aICH) on post-EVT outcomes. We sought to evaluate the effect of aICH on immediate and 90-day post-EVT neurological outcomes. METHODS: In this post-hoc analysis of the multicenter, prospective Blood Pressure after Endovascular Therapy (BEST) study we identified subjects with ICH following EVT. This population was divided into no ICH, aICH, and symptomatic ICH (sICH). Associations with 90-day modified Rankin Scale (mRS) dichotomized by functional independence (0-2 vs 3-6) and early neurological recovery (ENR) were determined using univariate/multivariate logistic regression models. RESULTS: Of 485 patients enrolled in BEST, 446 had 90-day follow-up data available. 92 (20.6%) developed aICH, and 18 (4%) developed sICH. Compared with those without ICH, aICH was not associated with worse 90-day outcome or lower ENR (OR 0.84 [0.53-1.35], P=0.55, aOR 0.84 [0.48-1.44], P=0.53 for 90-day mRS 0-2; OR 0.77 [0.48-1.23], P=0.34, aOR 0.72 [0.43-1.22] for ENR). aICH was not associated with 90-day outcome or ENR in patients with mTICI ≥2 b (OR 0.78 [0.48-1.26], P=0.33 for 90-day mRS 0-2; OR 0.89 [0.69-1.12], P=0.15 for ENR). A higher proportion of patients with aICH had mTICI ≥2 b than those without ICH (97%vs 87%, P=0.01). CONCLUSIONS: aICH was not associated with worse outcomes in patients with large-vessel stroke treated with EVT. aICH was more frequent in patients with successful recanalization. Further validation of our findings in large cohort studies of EVT-treated patients is warranted.

Impact of Neurovascular Comorbidities and Complications on Outcomes After Procedural Management of Intracranial Aneurysm: Part 2, Ruptured Intracranial Aneurysm.

OBJECTIVE: We aim to define the dynamic interplay between neurovascular-specific comorbidities and in-hospital complications on outcomes (functional outcome and mortality), length of stay (LOS), and cost of hospital stay. METHODS: The 2012-2015 National Inpatient Sample (NIS) was queried for intracranial aneurysm treatment after subarachnoid hemorrhage using International Classification of Diseases, Ninth Revision codes. Neurovascular comorbidity index (NCI) was aggregated. NIS-Subarachnoid Hemorrhage Severity Score (NIS-SSS) was used as a Hunt-Hess grade proxy. In-hospital complications were medical complications, surgical complications, seizures, and cerebral vasospasm. Outcomes were functional outcome (modified Rankin Scale [mRS]-equivalent measure), in-hospital mortality, LOS, and cost. Multivariable logistic regression models were built for mRS equivalent and in-hospital mortality. Multivariable linear regression models in log scale were built for LOS and cost. RESULTS: A total of 5353 patients were included. The median NCI was 4.00 (interquartile range [IQR], 0.00-7.00) and 2882 patients (54%) had in-hospital complication. Higher NCI (odds ratio [OR], 1.13 if NCI = 1; OR, 2.05 if NCI = 7; P < 0.001) was associated with any complication, seizure (OR, 1.11, NCI = 1; OR, 1.60, NCI = 7; P < 0.001), medical complication (OR, 1.18, NCI = 1; OR, 2.50, NCI = 7; P < 0.001), surgical complication (OR, 1.13, NCI = 1; OR, 1.91, NCI = 7; P < 0.001), and cerebral vasospasm (OR, 1.09, NCI = 1; OR, 1.49, NCI = 7; P < 0.001). Patients with higher NCI (OR, 1.06, NCI = 1; OR, 1.95, NCI = 7; P < 0.001) or with in-hospital complication (P < 0.001) had poorer mRS equivalent outcome. Similar trends were observed for other outcomes including in-hospital mortality, LOS, and cost. CONCLUSIONS: Neurovascular comorbidities are the primary driver of poor mRS equivalent outcome, in-hospital mortality, higher LOS, and higher cost after ruptured intracranial aneurysm procedural treatment. The conditional event of complication influences patients with moderate comorbidities more so than those with low or high comorbidities.

Neighborhood Socioeconomic Status and Mechanical Thrombectomy Outcomes.

BACKGROUND/PURPOSE: Our study aimed to assess the impacts of neighborhood socioeconomic status on mechanical thrombectomy (MT) outcomes for acute ischemic stroke (AIS). METHODS: We conducted a prospective observational study of consecutive adult AIS patients treated with MT at one US comprehensive stroke center from 2012 to 2018. A composite neighborhood socioeconomic score (nSES) was created using patient home address, median household income, percentage of households with interest, dividend, or rental income, median value of housing units, percentage of persons 25 or older with high school degrees, college degrees or holding executive, managerial or professional specialty occupations. Using this score, patients were divided into low, middle and high nSES tertiles. Outcomes included 90-day functional independence, in-hospital mortality, length of hospital stay, discharge location, time to recanalization, successful recanalization, and symptomatic intracranial hemorrhage (sICH). RESULTS: 328 patients were included. Between the three nSES groups, proportion of White patients, time-to-recanalization and admission NIH stroke scale differed significantly (p<0.05). Patients in the high nSES tertile were more likely to be functionally dependent at 90 days (unadjusted OR, 95% CI, 1.91 [1.10, 3.36]) and were less likely to die in the hospital (unadjusted OR, 95% CI, 0.46, [0.20, 0.98]). Further, patients in the high nSES tertile had decreased times to recanalization (median time in minutes, low=335, mid=368, high=297, p=0.04). However, after adjusting for variance in race and severity of stroke, the differences in clinical outcomes were not significant. CONCLUSION: This study highlights how unadjusted neighborhood socioeconomic status is significantly associated with functional outcome, mortality, and time-to-recanalization following MT for AIS. Since adjustment modifies the significant association, the socioeconomic differences may be influenced by differences in pre-hospital factors that drive severity of stroke and time to recanalization. Better understanding of the interplay of these factors may lead to timelier evaluation and improvement in patient outcomes.

CYP2C19 Loss-of-Function is Associated with Increased Risk of Ischemic Stroke after Transient Ischemic Attack in Intracranial Atherosclerotic Disease.

OBJECTIVES: Intracranial atherosclerotic disease (ICAD) is responsible for 8-10% of acute ischemic strokes, and resistance to antiplatelet therapy is prevalent. CYP2C19 gene loss-of-function (up to 45% of patients) causes clopidogrel resistance. For patients with asymptomatic ICAD and ICAD characterized by transient ischemic attack (TIA), this study measures the effect of CYP2C19 loss-of-function on ischemic stroke risk during clopidogrel therapy. MATERIALS AND METHODS: From a deidentified database of medical records, patients were selected with ICD-9/10 code for ICAD, availability of CYP2C19 genotype, clopidogrel exposure, and established patient care. Dual-antiplatelet therapy patients were included. Patients with prior ischemic stroke, other neurovascular condition, intracranial angioplasty/stenting, or observation time <1 month were excluded. Time-to-event analysis using Cox regression was conducted to model first-time ischemic stroke events based on CYP2C19 loss-of-function allele and adjusted for age, gender, race, length of aspirin, length of concurrent antiplatelet/anticoagulant treatment, diabetes, coagulopathy, hypertension, heart disease, atrial fibrillation, and lipid disorder. Subset analyses were performed for asymptomatic and post-TIA subtypes of ICAD. RESULTS: A total of 337 patients were included (median age 68, 58% male, 88% Caucasian, 26% CYP2C19 loss-of-function). A total of 161 (47.8%) patients had TIA at time of ICAD diagnosis, while 176 (52.2%) were asymptomatic. First-time ischemic stroke was observed among 20 (12.4%) post-TIA ICAD patients and 17 (9.7%) asymptomatic ICAD patients. Median observation time was 2.82 [IQR 1.13-5.17] years. CYP2C19 loss-of-function allele was associated with ischemic stroke event (HR 2.2, 95% CI 1.1-4.3, p=0.020) after adjustment. Post-TIA ICAD patients had a higher risk of ischemic stroke from CYP2C19 loss-of-function (HR 3.4, 95% CI 1.4-8.2, p=0.006). CONCLUSIONS: CYP2C19 loss-of-function was associated with 3-fold increased risk of first-time ischemic stroke for ICAD patients treated with clopidogrel after TIA. This effect was not observed for asymptomatic ICAD. CYP2C19-guided antiplatelet selection may improve stroke prevention in ICAD after TIA.

Impact of Neurovascular Comorbidities and Complications on Outcomes After Procedural Management of Intracranial Aneurysm: Part 1, Unruptured Intracranial Aneurysm.

OBJECTIVE: This study investigates the relationship between neurovascular comorbidities and in-hospital complications in determining functional outcome, mortality, length of stay (LOS), and cost of stay. METHODS: Patients were identified from the 2012-2015 National Inpatient Sample (NIS) using International Classification of Diseases, Ninth Revision codes for unruptured intracranial aneurysm (UIA) treatment in patients without subarachnoid hemorrhage. In-hospital complications were divided into medical complications, surgical complications, and seizures. Primary outcomes were functional outcome measured by modified Rankin Scale (mRS)-equivalent measure, in-hospital mortality, LOS, and cost. Multivariable logistic regression models were built for mRS-equivalent and in-hospital mortality. Multivariable linear regression models in log scale were built for LOS and cost. RESULTS: A total of 7398 procedurally managed patients with UIA were included (median age, 58 years; 75% female; 66% white; 43% private insurance). Higher Neurovascular Comorbidities Index (NCI) was associated with seizure (odds ratio [OR], 1.11 if NCI = 1; OR, 2.49 if NCI = 7; P < 0.001), medical complication (OR, 1.21, NCI = 1; OR, 3.46, NCI = 7; P < 0.001), and surgical complication (OR, 1.25, NCI = 1; OR, 3.47, NCI = 7; P < 0.001). NCI remained significantly predictive of poor mRS-equivalent outcome (OR, 1.20, NCI = 1; OR, 5.79, NCI = 7; P < 0.001), in-hospital mortality (OR, 1.98, NCI = 1; OR, 10.9, NCI = 7; P < 0.001), LOS (coefficient dependent on multiple variables, P < 0.001), and cost (coefficient dependent on multiple variables, P < 0.001) after adjustment. CONCLUSIONS: Neurovascular comorbidities are the primary driver of poor mRS-equivalent outcome, in-hospital mortality, higher LOS, and higher cost after procedural treatment of UIA. The conditional event of complication influences patients with fewer comorbidities more so than those with no comorbidities or high comorbidities. It is imperative to precisely account for these factors to optimize targeted resource allocation and increase the value of care for patients with UIA.

Improved Cerebral Arteriovenous Malformation Obliteration With 3-Dimensional Rotational Digital Subtraction Angiography for Radiosurgical Planning: A Retrospective Cohort Study.

BACKGROUND: Stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs) is well-established. Radiographic advantages exist for 3-dimensional rotational digital subtraction angiography (3DRA) over 2-dimensional digital subtraction angiography (2D DSA) in delineating AVM nidus structure for SRS treatment planning. However, currently there is limited to no data directly comparing 2D DSA versus 3DRA in terms of patient outcomes. OBJECTIVE: To investigate whether the use of 3DRA over 2D DSA in radiosurgical treatment planning for AVMs associates with improved clinical outcomes. METHODS: All AVM patients treated with SRS at our institution between the years 2000 and 2018 were identified. Primary outcomes were obliteration rates and time to obliteration (TTO); secondary outcomes included rates of post-SRS hemorrhage, salvage therapy, and symptomatic radionecrosis. A minimum of 12 mo of follow-up imaging/angiogram post-SRS was required, or alternatively evidence of obliteration on angiogram prior to 12 mo post-SRS. Single predictor and multivariable Cox regression and logistic regression models were constructed to test for association between radiographic, clinical, and treatment factors with outcomes. RESULTS: A total of 75 patients were included. Total 17 patients received 3DRA and 58 patients received 2D DSA, with a median follow-up of 3.29 yr. The 3DRA is significantly associated with improved TTO on single predictor (HR 2.87, 1.29-6.12; P = .0109) and multivariable analysis (HR 2.448, 1.076-5.750; P = .0330) and increased odds of achieving obliteration by 3 yr post-SRS on single predictor analysis (OR 6.044, 1.405-26.009; P = .0157). CONCLUSION: The 3DRA over 2D DSA in SRS treatment planning for AVMs may result in improved TTO and 3-yr obliteration rates. Further investigation and prospective study are warranted.

Mechanical Thrombectomy in Ischemic Stroke Patients with Severe Pre-Stroke Disability.

Frequency and outcomes of mechanical thrombectomy (MT) in clinical practice for patients with severe pre-stroke disability are largely unknown. In this case series, we aim to describe the disability make-up and outcomes of 33 patients with severe pre-stroke disability undergoing MT. Patients with a permanent, severe, pre-stroke disability (modified Rankin Score, mRS, 4-5) were identified from a prospectively-maintained database of consecutive, MT-treated, anterior circulation acute ischemic stroke patients at two comprehensive stroke centers in the United States. We present details on the cause of disability and socio-demographic status as well as procedural and functional outcomes. This study, despite the lack of inferential testing due to limited sample size, provides insight into demographics and outcomes of MT-treated patients with severe pre-stroke disability. Rate of return to functional baseline as well as rates of procedural success and complications were comparable to that reported in the literature for patients without any pre-existing disability.

Mechanical Thrombectomy in Patients With Ischemic Stroke With Prestroke Disability.

Background and Purpose- We aimed to compare functional and procedural outcomes of patients with acute ischemic stroke with none-to-minimal (modified Rankin Scale [mRS] score, 0-1) and moderate (mRS score, 2-3) prestroke disability treated with mechanical thrombectomy. Methods- Consecutive adult patients undergoing mechanical thrombectomy for an anterior circulation stroke were prospectively identified at 2 comprehensive stroke centers from 2012 to 2018. Procedural and 90-day functional outcomes were compared among patients with prestroke mRS scores 0 to 1 and 2 to 3 using χ2, logistic, and linear regression tests. Primary outcome and significant differences in secondary outcomes were adjusted for prespecified covariates. Results- Of 919 patients treated with mechanical thrombectomy, 761 were included and 259 (34%) patients had moderate prestroke disability. Ninety-day mRS score 0 to 1 or no worsening of prestroke mRS was observed in 36.7% and 26.7% of patients with no-to-minimal and moderate prestroke disability, respectively (odds ratio, 0.63 [0.45-0.88], P=0.008; adjusted odds ratio, 0.90 [0.60-1.35], P=0.6). No increase in the disability at 90 days was observed in 22.4% and 26.7%, respectively. Rate of symptomatic intracerebral hemorrhage (7.3% versus 6.2%, P=0.65), successful recanalization (86.7% versus 83.8%, P=0.33), and median length of hospital stay (5 versus 5 days, P=0.06) were not significantly different. Death by 90 days was higher in patients with moderate prestroke disability (14.3% versus 40.3%; odds ratio, 4.06 [2.82-5.86], P<0.001; adjusted odds ratio, 2.83 [1.84, 4.37], P<0.001). Conclusions- One-third of patients undergoing mechanical thrombectomy had a moderate prestroke disability. There was insufficient evidence that functional and procedural outcomes were different between patients with no-to-minimal and moderate prestroke disability. Patients with prestroke disability were more likely to die by 90 days.

Classifying intracranial stenosis disease severity from functional MRI data using machine learning.

Translation of many non-invasive hemodynamic MRI methods to cerebrovascular disease patients has been hampered by well-known artifacts associated with delayed blood arrival times and reduced microvascular compliance. Using machine learning and support vector machine (SVM) algorithms, we investigated whether arrival time-related artifacts in these methods could be exploited as novel contrast sources to discriminate angiographically confirmed stenotic flow territories. Intracranial steno-occlusive moyamoya patients (n = 53; age = 45 ± 14.2 years; sex = 43 F) underwent (i) catheter angiography, (ii) anatomical MRI, (iii) cerebral blood flow (CBF)-weighted arterial spin labeling, and (iv) cerebrovascular reactivity (CVR)-weighted hypercapnic blood-oxygenation-level-dependent MRI. Mean, standard deviation (std), and 99th percentile of CBF, CVR, CVRDelay, and CVRMax were calculated in major anterior and posterior flow territories perfused by vessels with vs. without stenosis (≥70%) confirmed by catheter angiography. These and demographic variables were input into SVMs to evaluate discriminatory capacity for stenotic flow territories using k-fold cross-validation and receiver-operating-characteristic-area-under-the-curve to quantify variable combination relevance. Anterior circulation CBF-std, attributable to heterogeneous endovascular signal and prolonged arterial transit times, was the best performing single variable and CVRDelay-mean and CBF-std, both reflective of delayed vascular compliance, were a high-performing two-variable combination (specificity = 0.67; sensitivity = 0.75). Findings highlight the relevance of hemodynamic imaging and machine learning for identifying cerebrovascular impairment.