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).

Cerebrovascular reactivity dispersion as a new biomarker of recent stroke symptomatology in moyamoya.

Background: Moyamoya disease (MMD) is a non-atherosclerotic intracranial steno-occlusive condition placing patients at high risk for ischemic stroke. Direct and indirect surgical revascularization can improve blood flow in MMD; however, randomized trials demonstrating efficacy have not been performed and biomarkers of parenchymal hemodynamic impairment are needed to triage patients for interventions and evaluate post-surgical efficacy. We test the hypothesis that hypercapnia-induced maximum cerebrovascular reactivity (CVR MAX ) and the more novel indicator cerebrovascular reactivity (CVR) response time (CVR DELAY ), both assessed from time-regression analyses of non-invasive hypercapnic imaging, correlate with recent focal ischemic symptoms. Methods: Hypercapnic reactivity medical resonance imaging (blood oxygenation level-dependent; echo time=35ms; spatial resolution=3.5×3.5×3.5mm) and catheter angiography assessments of cortical reserve capacity and vascular patency, respectively, in MMD participants (n=73) were performed in sequence. Time regression analyses were applied to quantify CVR MAX and CVR DELAY . Symptomatology information for each hemisphere (n=109) was categorized into symptomatic (ischemic symptoms within six months) or asymptomatic (no history of ischemic symptoms) and logistic regression analysis assessed the association of CVR metrics with ischemic symptoms after controlling for age and sex. Results: Symptomatic hemispheres displayed lengthened CVR DELAY (p<0.001), which was more discriminatory between hemispheres than CVR MAX (p=0.037). CVR DELAY (p<0.001), but not CVR MAX (p=0.127), was found to be sensitively related to age in asymptomatic tissue (0.33-unit increase/year); age-dependent normative ranges are presented to enable quantitative assessment of patient-specific impairment. Furthermore, the area under the receiver operating characteristic curves shows that CVR DELAY predicts ischemic symptoms (p<0.001), whereas CVR MAX does not (p=0.056). Conclusion: Findings support that CVR metrics are uniquely altered in hemispheres with recent ischemic symptoms, motivating the investigation of CVR as a surrogate of ischemic symptomatology and treatment efficacy.

Choroid plexus vascular reactivity in moyamoya: Implications for choroid plexus regulation in ischemic stress.

BACKGROUND AND PURPOSE: Choroid plexus (ChP) hyperemia has been observed in patients with intracranial vasculopathy and to reduce following successful surgical revascularization. This observation may be attributable to impaired vascular reserve of the ChP or other factors, such as the ChP responding to circulating markers of stress. We extend this work to test the hypothesis that vascular reserve of the ChP is unrelated to intracranial vasculopathy. METHODS: We performed hypercapnic reactivity (blood oxygenation level-dependent; echo time = 35 ms; spatial resolution = 3.5 × 3.5 × 3.5 mm, repetition time = 2000 ms) and catheter angiography assessments of ChP reserve capacity and vascular patency in moyamoya patients (n = 53) with and without prior surgical revascularization. Time regression analyses quantified maximum cerebrovascular reactivity and reactivity delay time in ChP and cortical flow territories of major intracranial vessels with steno-occlusion graded as <70%, 70%-99%, and occlusion using Warfarin-Aspirin-Symptomatic-Intracranial-Disease stenosis grading criteria. Analysis of variance (significance: two-sided Bonferroni-corrected p < .05) was applied to evaluate cortical and ChP reactivity, after accounting for end-tidal carbon dioxide change, for differing vasculopathy categories. RESULTS: In patients without prior revascularization, arterial vasculopathy was associated with reduced cortical reactivity and lengthened reactivity delay (p ≤ .01), as expected. Regardless of surgical history, the ChP reactivity metrics were not significantly related to the degree of proximal stenosis, consistent with ChP reactivity being largely preserved in this population. CONCLUSIONS: Findings are consistent with ChP reactivity in moyamoya not being dependent on observed vasculopathy. Future work may investigate the extent to which ChP hyperemia in chronic ischemia reflects circulating markers of glial or ischemic stress.

Blood Pressure Management After Endovascular Therapy for Acute Ischemic Stroke: The BEST-II Randomized Clinical Trial.

Importance: The effects of moderate systolic blood pressure (SBP) lowering after successful recanalization with endovascular therapy for acute ischemic stroke are uncertain. Objective: To determine the futility of lower SBP targets after endovascular therapy (<140 mm Hg or 160 mm Hg) compared with a higher target (≤180 mm Hg). Design, Setting, and Participants: Randomized, open-label, blinded end point, phase 2, futility clinical trial that enrolled 120 patients with acute ischemic stroke who had undergone successful endovascular therapy at 3 US comprehensive stroke centers from January 2020 to March 2022 (final follow-up, June 2022). Intervention: After undergoing endovascular therapy, participants were randomized to 1 of 3 SBP targets: 40 to less than 140 mm Hg, 40 to less than 160 mm Hg, and 40 to 180 mm Hg or less (guideline recommended) group, initiated within 60 minutes of recanalization and maintained for 24 hours. Main Outcomes and Measures: Prespecified multiple primary outcomes for the primary futility analysis were follow-up infarct volume measured at 36 (±12) hours and utility-weighted modified Rankin Scale (mRS) score (range, 0 [worst] to 1 [best]) at 90 (±14) days. Linear regression models were used to test the harm-futility boundaries of a 10-mL increase (slope of 0.5) in the follow-up infarct volume or a 0.10 decrease (slope of -0.005) in the utility-weighted mRS score with each 20-mm Hg SBP target reduction after endovascular therapy (1-sided α = .05). Additional prespecified futility criterion was a less than 25% predicted probability of success for a future 2-group, superiority trial comparing SBP targets of the low- and mid-thresholds with the high-threshold (maximum sample size, 1500 with respect to the utility-weighted mRS score outcome). Results: Among 120 patients randomized (mean [SD] age, 69.6 [14.5] years; 69 females [58%]), 113 (94.2%) completed the trial. The mean follow-up infarct volume was 32.4 mL (95% CI, 18.0 to 46.7 mL) for the less than 140-mm Hg group, 50.7 mL (95% CI, 33.7 to 67.7 mL), for the less than 160-mm Hg group, and 46.4 mL (95% CI, 24.5 to 68.2 mL) for the 180-mm Hg or less group. The mean utility-weighted mRS score was 0.51 (95% CI, 0.38 to 0.63) for the less than 140-mm Hg group, 0.47 (95% CI, 0.35 to 0.60) for the less than 160-mm Hg group, and 0.58 (95% CI, 0.46 to 0.71) for the high-target group. The slope of the follow-up infarct volume for each mm Hg decrease in the SBP target, adjusted for the baseline Alberta Stroke Program Early CT score, was -0.29 (95% CI, -0.81 to ∞; futility P = .99). The slope of the utility-weighted mRS score for each mm Hg decrease in the SBP target after endovascular therapy, adjusted for baseline utility-weighted mRS score, was -0.0019 (95% CI, -∞ to 0.0017; futility P = .93). Comparing the high-target SBP group with the lower-target groups, the predicted probability of success for a future trial was 25% for the less than 140-mm Hg group and 14% for the 160-mm Hg group. Conclusions and Relevance: Among patients with acute ischemic stroke, lower SBP targets less than either 140 mm Hg or 160 mm Hg after successful endovascular therapy did not meet prespecified criteria for futility compared with an SBP target of 180 mm Hg or less. However, the findings suggested a low probability of benefit from lower SBP targets after endovascular therapy if tested in a future larger trial. Trial Registration: ClinicalTrials.gov Identifier: NCT04116112.

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.

Flat-panel dual-energy head computed tomography in the angiography suite after thrombectomy for acute stroke: A clinical feasibility study.

BACKGROUND: Management of large vessel occlusion (LVO) patients after thrombectomy is affected by the presence of intracranial hemorrhage (ICH) on post-procedure imaging. Differentiating contrast staining from hemorrhage on post-procedural imaging has been facilitated by dual-energy computed tomography (DECT), traditionally performed in dedicated computed tomography (CT) scanners with subsequent delays in treatment. We employed a novel method of DECT using the Siemens cone beam CT (DE-CBCT) in the angiography suite to evaluate for post-procedure ICH and contrast extravasation. METHODS: After endovascular treatment for LVO was performed and before the patient was removed from the operating table, DE-CBCT was performed using the Siemens Q-biplane system, with two separate 20-second CBCT scans at two energy levels: 70 keV (standard) and 125 keV with tin filtration (nonstandard). Post-procedurally, patients also underwent a standard DECT using Siemens SOMATOM Force CT scanner. Two independent reviewers blindly evaluated the DE-CBCT and DECT for hemorrhage and contrast extravasation. RESULTS: We successfully performed intra-procedural DE-CBCT in 10 subjects with no technical failure. The images were high-quality and subjectively useful to differentiate contrast from hemorrhage. The one hemorrhage seen on standard DECT was very small and clinically silent. The interrater reliability was 100% for both contrast and hemorrhage detection. CONCLUSION: We demonstrate that intra-procedural DE-CBCT after thrombectomy is feasible and provides clinically meaningful images. There was close agreement between findings on DE-CBCT and standard DECT. Our findings suggest that DE-CBCT could be used in the future to improve stroke thrombectomy patient workflow and to more efficiently guide the postoperative management of these patients.

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.

Presurgical Magnetic Resonance Imaging Indicators of Revascularization Response in Adults With Moyamoya Vasculopathy.

BACKGROUND: Moyamoya is a progressive intracranial vasculopathy, primarily affecting distal segments of the internal carotid and middle cerebral arteries. Treatment may comprise angiogenesis-inducing surgical revascularization; however, lack of randomized trials often results in subjective treatment decisions. HYPOTHESIS: Compensatory presurgical posterior vertebrobasilar artery (VBA) flow-territory reactivity, including greater cerebrovascular reactivity (CVR) and reduced vascular delay time, portends greater neoangiogenic response verified on digital subtraction angiography (DSA) at 1-year follow-up. STUDY TYPE: Prospective intervention cohort. SUBJECTS: Thirty-one patients with moyamoya (26 females; age = 45 ± 13 years; 41 revascularized hemispheres). METHODS: Anatomical MRI, hypercapnic CVR MRI, and DSA acquired presurgically in adult moyamoya participants scheduled for clinically indicated surgical revascularization. One-year postsurgery, DSA was repeated to evaluate collateralization. FIELD STRENGTH: 3 T. SEQUENCE: Hypercapnic T 2 * -weighted gradient-echo blood-oxygenation-level-dependent, T2 -weighted turbo-spin-echo fluid-attenuated-inversion-recovery, T1 -weighted magnetization-prepared-rapid-gradient-echo, and T2 -weighted diffusion-weighted-imaging. ASSESSMENT: Presurgical maximum CVR and response times were evaluated in VBA flow-territories. Revascularization success was determined using an ordinal scoring system of neoangiogenic collateralization from postsurgical DSA by two cerebrovascular neurosurgeons (R.V.C. with 8 years of experience; M.R.F. with 9 years of experience) and one neuroradiologist (L.T.D. with 8 years of experience). Stroke risk factors (age, sex, race, vasculopathy, and diabetes) were recorded. STATISTICAL TESTS: Fisher's exact and Wilcoxon rank-sum tests were applied to compare presurgical variables between cohorts with angiographically confirmed good (>1/3 middle cerebral artery [MCA] territory revascularized) vs. poor (<1/3 MCA territory revascularized) outcomes. SIGNIFICANCE: two-sided P < 0.05. Normalized odds ratios (ORs) were calculated. RESULTS: Criteria for good collateralization were met in 25 of the 41 revascularized hemispheres. Presurgical normalized VBA flow-territory CVR was significantly higher in those with good (1.12 ± 0.13 unitless) vs. poor (1.04 ± 0.05 unitless) outcomes. Younger (OR = -0.60 ± 0.67) and White (OR = -1.81 ± 1.40) participants had highest revascularization success (good outcomes: age = 42 ± 14 years, race = 84% White; poor outcomes: age = 49 ± 11 years, race = 44% White). DATA CONCLUSION: Presurgical MRI-measures of VBA flow-territory CVR are highest in moyamoya participants with better angiographic responses to surgical revascularization. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 4.

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.

Choroid plexus perfusion in sickle cell disease and moyamoya vasculopathy: Implications for glymphatic flow.

Cerebrospinal fluid (CSF) and interstitial fluid exchange have been shown to increase following pharmacologically-manipulated increases in cerebral arterial pulsatility, consistent with arterial pulsatility improving CSF circulation along perivascular glymphatic pathways. The choroid plexus (CP) complexes produce CSF, and CP activity may provide a centralized indicator of perivascular flow. We tested the primary hypothesis that elevated cortical cerebral blood volume and flow, present in sickle cell disease (SCD), is associated with fractionally-reduced CP perfusion relative to healthy adults, and the supplementary hypothesis that reduced arterial patency, present in moyamoya vasculopathy, is associated with elevated fractional CP perfusion relative to healthy adults. Participants (n = 75) provided informed consent and were scanned using a 3-Tesla arterial-spin-labeling MRI sequence for CP and cerebral gray matter (GM) perfusion quantification. ANOVA was used to calculate differences in CP-to-GM perfusion ratios between groups, and regression analyses applied to evaluate the dependence of the CP-to-GM perfusion ratio on group after co-varying for age and sex. ANOVA yielded significant (p < 0.001) group differences, with CP-to-GM perfusion ratios increasing between SCD (ratio = 0.93 ± 0.28), healthy (ratio = 1.04 ± 0.32), and moyamoya (ratio = 1.29 ± 0.32) participants, which was also consistent with regression analyses. Findings are consistent with CP perfusion being inversely associated with cortical perfusion.

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.

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.