Higher Hospital Frailty Risk Score Is Associated With Increased Risk of Stroke: Observational and Genetic Analyses.

BACKGROUND: Frailty is a prevalent state associated with several aging-related traits and conditions. The relationship between frailty and stroke remains understudied. Here we aim to investigate whether the hospital frailty risk score (HFRS) is associated with the risk of stroke and determine whether a significant association between genetically determined frailty and stroke exists. DESIGN: Observational study using data from All of Us research program and Mendelian Randomization analyses. METHODS: Participants from All of Us with available electronic health records were selected for analysis. All of Us began national enrollment in 2018 and is expected to continue for at least 10 years. All of Us is recruiting members of groups that have traditionally been underrepresented in research. All participants provided informed consent at the time of enrollment, and the date of consent was recorded for each participant. Incident stroke was defined as stroke event happening on or after the date of consent to the All of Us study HFRS was measured with a 3-year look-back period before the date of consent for stroke risk. The HFRS was stratified into 4 categories: no-frailty (HFRS=0), low (HFRS ≥1 and <5), intermediate (≥5 and <15), and high (HFRS ≥15). Last, we implemented Mendelian Randomization analyses to evaluate whether genetically determined frailty is associated with stroke risk. RESULTS: Two hundred fifty-three thousand two hundred twenty-six participants were at risk of stroke. In multivariable analyses, frailty status was significantly associated with risk of any (ischemic or hemorrhagic) stroke following a dose-response way: not-frail versus low HFRS (HR, 4.9 [CI, 3.5-6.8]; P<0.001), not-frail versus intermediate HFRS (HR, 11.4 [CI, 8.3-15.7]; P<0.001) and not-frail versus high HFRS (HR, 42.8 [CI, 31.2-58.6]; P<0.001). We found similar associations when evaluating ischemic and hemorrhagic stroke separately (P value for all comparisons <0.05). Mendelian Randomization confirmed this association by indicating that genetically determined frailty was independently associated with risk of any stroke (OR, 1.45 [95% CI, 1.15-1.84]; P=0.002). CONCLUSIONS: Frailty, based on the HFRS was associated with higher risk of any stroke. Mendelian Randomization analyses confirmed this association providing evidence to support a causal relationship.

Genetically Determined Low-Density Lipoprotein Cholesterol and Risk of Subarachnoid Hemorrhage.

We evaluated whether genetically elevated low-density lipoprotein cholesterol (LDL-C) levels are associated with lower risk of intracranial aneurysms and subarachnoid hemorrhage (IA/SAH). We conducted a 2-sample Mendelian randomization (MR) study. Our primary analysis used the inverse-variance weighted method. In secondary analyses, we implemented the MR-PRESSO method, restricted our analysis to LDL-C-specific instruments, and performed multivariate MR. A 1-mmol/l increase in genetically instrumented LDL-C levels was associated with a 17% lower risk of IA/SAH (odds ratio = 0.83, 95% confidence interval = 0.73-0.94, p = 0.004). Results remained consistent in secondary and multivariate analyses (all p < 0.05). Our results provide evidence for an inverse causal relationship between LDL-C levels and risk of IA/SAH. ANN NEUROL 2022;91:145-149.

Deep Learning Applications for Acute Stroke Management.

Brain imaging is essential to the clinical care of patients with stroke, a leading cause of disability and death worldwide. Whereas advanced neuroimaging techniques offer opportunities for aiding acute stroke management, several factors, including time delays, inter-clinician variability, and lack of systemic conglomeration of clinical information, hinder their maximal utility. Recent advances in deep machine learning (DL) offer new strategies for harnessing computational medical image analysis to inform decision making in acute stroke. We examine the current state of the field for DL models in stroke triage. First, we provide a brief, clinical practice-focused primer on DL. Next, we examine real-world examples of DL applications in pixel-wise labeling, volumetric lesion segmentation, stroke detection, and prediction of tissue fate postintervention. We evaluate recent deployments of deep neural networks and their ability to automatically select relevant clinical features for acute decision making, reduce inter-rater variability, and boost reliability in rapid neuroimaging assessments, and integrate neuroimaging with electronic medical record (EMR) data in order to support clinicians in routine and triage stroke management. Ultimately, we aim to provide a framework for critically evaluating existing automated approaches, thus equipping clinicians with the ability to understand and potentially apply DL approaches in order to address challenges in clinical practice. ANN NEUROL 2022;92:574-587.

Hospital Revisits for Post-Ischemic Stroke Epilepsy after Acute Stroke Interventions.

OBJECTIVES: Improvements in acute stroke care have led to an increase in ischemic stroke survivors, who are at risk for development of post-ischemic stroke epilepsy (PISE). The impact of therapies such as thrombectomy and thrombolysis on risk of hospital revisits for PISE is unclear. We utilized administrative data to investigate the association between stroke treatment and PISE-related visits. MATERIALS AND METHODS: Using claims data from California, New York, and Florida, we performed a retrospective analysis of adult survivors of acute ischemic strokes. Patients with history of epilepsy, trauma, infections, or tumors were excluded. Included patients were followed for a primary outcome of revisits for seizures or epilepsy. Cox proportional hazards regression was used to identify covariates associated with PISE. RESULTS: In 595,545 included patients (median age 74 [IQR 21], 52% female), the 6-year cumulative rate of PISE-related revisit was 2.20% (95% CI 2.16-2.24). In multivariable models adjusting for demographics, comorbidities, and indicators of stroke severity, IV-tPA (HR 1.42, 95% CI 1.31-1.54, p<0.001) but not MT (HR 1.62, 95% CI 0.90-1.50, p=0.2) was associated with PISE-related revisit. Patients who underwent decompressive craniectomy experienced a 2-fold increase in odds for returning with PISE (HR 2.35, 95% CI 1.69-3.26, p<0.001). In-hospital seizures (HR 4.06, 95% CI 3.76-4.39, p<0.001) also elevated risk for PISE. SIGNIFICANCE: We demonstrate that ischemic stroke survivors who received IV-tPA, underwent decompressive craniectomy, or experienced acute seizures were at increased risk PISE-related revisit. Close attention should be paid to these patients with increased potential for long-term development of and re-hospitalization for PISE.

Genetically Determined Smoking Behavior and Risk of Nontraumatic Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Animal and observational studies indicate that smoking is a risk factor for aneurysm formation and rupture, leading to nontraumatic subarachnoid hemorrhage (SAH). However, a definitive causal relationship between smoking and the risk of SAH has not been established. Using Mendelian randomization (MR) analyses, we tested the hypothesis that smoking is causally linked to the risk of SAH. METHODS: We conducted a 1-sample MR study using data from the UK Biobank, a large cohort study that enrolled over 500 000 Britons aged 40 to 69 from 2006 to 2010. Participants of European descent were included. SAH cases were ascertained using a combination of self-reported, electronic medical record, and death registry data. As the instrument, we built a polygenic risk score using independent genetic variants known to associate (P<5×10-8) with smoking behavior. This polygenic risk score represents the genetic susceptibility to smoking initiation. The primary MR analysis utilized the ratio method. Secondary MR analyses included the inverse variance weighted and weighted median methods. RESULTS: A total of 408 609 study participants were evaluated (mean age, 57 [SD 8], female sex, 220 937 [54%]). Among these, 132 566 (32%) ever smoked regularly, and 904 (0.22%) had a SAH. Each additional SD of the smoking polygenic risk score was associated with 21% increased risk of smoking (odds ratio [OR], 1.21 [95% CI, 1.20-1.21]; P<0.001) and a 10% increased risk of SAH (OR, 1.10 [95% CI, 1.03-1.17]; P=0.006). In the primary MR analysis, genetic susceptibility to smoking was associated with a 63% increase in the risk of SAH (OR, 1.63 [95% CI, 1.15-2.31]; P=0.006). Secondary analyses using the inverse variance weighted method (OR, 1.57 [95% CI, 1.13-2.17]; P=0.007) and the weighted median method (OR, 1.74 [95% CI, 1.06-2.86]; P=0.03) yielded similar results. There was no significant pleiotropy (MR-Egger intercept P=0.39; MR Pleiotropy Residual Sum and Outlier global test P=0.69). CONCLUSIONS: These findings provide evidence for a causal link between smoking and the risk of SAH.

Association of Serum IL-6 (Interleukin 6) With Functional Outcome After Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVES: IL-6 (interleukin 6) is a proinflammatory cytokine and an established biomarker in acute brain injury. We sought to determine whether admission IL-6 levels are associated with severity and functional outcome after spontaneous intracerebral hemorrhage (ICH). METHODS: We performed an exploratory analysis of the recombinant activated FAST trial (Factor VII for Acute ICH). Patients with admission serum IL-6 levels were included. Regression analyses were used to assess the associations between IL-6 and 90-day modified Rankin Scale. In secondary analyses, we used linear regression to evaluate the association between IL-6 and baseline ICH and perihematomal edema volumes. RESULTS: Of 841 enrolled patients, we included 552 (66%) with available admission IL-6 levels (mean age 64 [SD 13], female sex 203 [37%]). IL-6 was associated with poor outcome (modified Rankin Scale, 4-6; per additional 1 ng/L, odds ratio, 1.30 [95% CI, 1.04-1.63]; P=0.02) after adjustment for known predictors of outcome after ICH and treatment group. IL-6 was associated with ICH volume after adjustment for age, sex, and ICH location, and this association was modified by location (multivariable interaction, P=0.002), with a stronger association seen in lobar (ß, 12.51 [95% CI, 6.47-18.55], P<0.001) versus nonlobar (ß 5.32 [95% CI, 3.36-7.28], P<0.001) location. IL-6 was associated with perihematomal edema volume after adjustment for age, sex, ICH volume, and ICH location (ß 1.22 [95% CI, 0.15-2.29], P=0.03). Treatment group was not associated with IL-6 levels or outcome. CONCLUSIONS: In the FAST trial population, higher admission IL-6 levels were associated with worse 90-day functional outcome and larger ICH and perihematomal edema volumes.

Admission Hemoglobin Levels Are Associated With Functional Outcome in Spontaneous Intracerebral Hemorrhage.

OBJECTIVES: To test the hypothesis that admission hemoglobin levels are associated with outcome in primary, nontraumatic intracerebral hemorrhage. DESIGN: Individual patient data meta-analysis of three studies of intracerebral hemorrhage. SETTING: Two randomized clinical trials and one multiethnic observational study. PATIENTS: Patients with spontaneous, nontraumatic intracerebral hemorrhage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our exposure of interest was admission hemoglobin levels and the primary outcome was 3-month postintracerebral hemorrhage-dichotomized modified Rankin Scale (0-3 vs 4-6). Intermediate outcomes were admission hematoma volume and hematoma expansion defined as 6 mL or 33% increase in hemorrhage size on repeat CT. A total of 4,172 intracerebral hemorrhage patients were included in the study (mean age 63 [sd = 14]; female sex 1,668 [40%]). Each additional g/dL of admission hemoglobin was associated with 14% (odds ratio, 0.86; 95% CI, 0.82-0.91) and 7% (odds ratio, 0.93; 95% CI, 0.88-0.98) reductions in the risk of poor outcome in unadjusted and adjusted analyses, respectively. Dose-response analyses indicated a linear relationship between admission hemoglobin levels and poor outcome across the entire evaluated range (test-for-trend p < 0.001). No consistent associations were found between the admission hemoglobin levels and hematoma volume or hematoma expansion. CONCLUSIONS: Higher hemoglobin levels are associated with better outcome in intracerebral hemorrhage. Further research is needed to evaluate admission hemoglobin levels as both a therapeutic target and predictor of outcome.

Effects of Collateral Status on Infarct Distribution Following Endovascular Therapy in Large Vessel Occlusion Stroke.

BACKGROUND AND PURPOSE: We aim to examine effects of collateral status and post-thrombectomy reperfusion on final infarct distribution and early functional outcome in patients with anterior circulation large vessel occlusion ischemic stroke. METHODS: Patients with large vessel occlusion who underwent endovascular intervention were included in this study. All patients had baseline computed tomography angiography and follow-up magnetic resonance imaging. Collateral status was graded according to the criteria proposed by Miteff et al and reperfusion was assessed using the modified Thrombolysis in Cerebral Infarction (mTICI) system. We applied a multivariate voxel-wise general linear model to correlate the distribution of final infarction with collateral status and degree of reperfusion. Early favorable outcome was defined as a discharge modified Rankin Scale score ≤2. RESULTS: Of the 283 patients included, 129 (46%) had good, 97 (34%) had moderate, and 57 (20%) had poor collateral status. Successful reperfusion (mTICI 2b/3) was achieved in 206 (73%) patients. Poor collateral status was associated with infarction of middle cerebral artery border zones, whereas worse reperfusion (mTICI scores 0-2a) was associated with infarction of middle cerebral artery territory deep white matter tracts and the posterior limb of the internal capsule. In multivariate regression models, both mTICI (P<0.001) and collateral status (P<0.001) were among independent predictors of final infarct volumes. However, mTICI (P<0.001), but not collateral status (P=0.058), predicted favorable outcome at discharge. CONCLUSIONS: In this cohort of patients with large vessel occlusion stroke, both the collateral status and endovascular reperfusion were strongly associated with middle cerebral artery territory final infarct volumes. Our findings suggesting that baseline collateral status predominantly affected middle cerebral artery border zones infarction, whereas higher mTICI preserved deep white matter and internal capsule from infarction; may explain why reperfusion success-but not collateral status-was among the independent predictors of favorable outcome at discharge. Infarction of the lentiform nuclei was observed regardless of collateral status or reperfusion success.

Fixed Compared With Autoregulation-Oriented Blood Pressure Thresholds After Mechanical Thrombectomy for Ischemic Stroke.

Background and Purpose- Loss of cerebral autoregulation in the acute phase of ischemic stroke leaves patients vulnerable to blood pressure (BP) changes. Effective BP management after endovascular thrombectomy may protect the brain from hypoperfusion or hyperperfusion. In this observational study, we compared personalized, autoregulation-based BP targets to static systolic BP thresholds. Methods- We prospectively enrolled 90 patients undergoing endovascular thrombectomy for stroke. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy-derived tissue oxygenation (a cerebral blood flow surrogate) in response to changes in mean arterial pressure. The resulting autoregulatory index was used to trend the BP range at which autoregulation was most preserved. Percent time that mean arterial pressure exceeded the upper limit of autoregulation or decreased below the lower limit of autoregulation was calculated for each patient. Time above fixed systolic BP thresholds was computed in a similar fashion. Functional outcome was measured with the modified Rankin Scale at 90 days. Results- Personalized limits of autoregulation were successfully computed in all 90 patients (age 71.6±16.2, 47% female, mean National Institutes of Health Stroke Scale 13.9±5.7, monitoring time 28.0±18.4 hours). Percent time with mean arterial pressure above the upper limit of autoregulation associated with worse 90-day outcomes (odds ratio per 10% 1.84 [95% CI, 1.3-2.7] P=0.002), and patients with hemorrhagic transformation spent more time above the upper limit of autoregulation (10.9% versus 16.0%, P=0.042). Although there appeared to be a nonsignificant trend towards worse outcome with increasing time above systolic BP thresholds of 140 mm Hg and 160 mm Hg, the effect sizes were smaller compared with the personalized approach. Conclusions- Noninvasive determination of personalized BP thresholds for stroke patients is feasible. Deviation from these limits may increase risk of further brain injury and poor functional outcome. This approach may present a better strategy compared with the classical approach of maintaining systolic BP below a predetermined value, though a randomized trial is needed to determine the optimal approach for hemodynamic management.

CT Angiography for Triage of Patients with Acute Minor Stroke: A Cost-effectiveness Analysis.

Background Minor stroke is common and may represent up to two-thirds of cases of acute ischemic stroke. The cost-effectiveness of CT angiography in patients with minor stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤6) is not well established. Purpose To evaluate cost-effectiveness of CT angiography in the detection of large-vessel occlusion (LVO) in patients with acute minor stroke (NIHSS score ≤6). Materials and Methods A Markov decision-analytic model with a societal perspective was constructed. Three different management strategies were evaluated: (a) no vascular imaging and best medical management, (b) CT angiography for all patients and immediate thrombectomy for LVO after intravenous thrombolysis, and (c) CT angiography for all and best medical management (including intravenous thrombolysis, with rescue thrombectomy for patients with LVO and neurologic deterioration). One-way, two-way, and probabilistic sensitivity analyses were performed. Results Base-case calculation showed that CT angiography followed by immediate thrombectomy had the lowest cost ($346 007) and highest health benefits (9.26 quality-adjusted life-years [QALYs]). CT angiography followed by best medical management with possible rescue thrombectomy for patients with LVO had a slightly higher cost ($346 500) and lower health benefits (9.09 QALYs). No vascular imaging had the highest cost and lowest health benefits. The difference in health benefits compared with the CT angiography and immediate thrombectomy strategy was 0.39 QALY, which corresponds to 142 days in perfect health per patient. The conclusion was robust in a probabilistic sensitivity analysis. CT angiography was cost-effective when the probability of LVO was greater than 0.16% in patients with acute minor stroke. The net monetary benefit of performing CT angiography was higher in younger patients ($68 950 difference between CT angiography followed by immediate thrombectomy and no vascular imaging in 55-year-old patients compared with $20 931 in 85-year-old patients). Conclusion Screening for large-vessel occlusion with CT angiography in patients with acute minor stroke is cost-effective and associated with improved health outcomes. Undetected large-vessel occlusion in the absence of vascular imaging results in worse health outcomes and higher costs. © RSNA, 2020 Online supplemental material is available for this article.

Predictors of Extended Length of Stay Following Treatment of Unruptured Adult Cerebral Aneurysms: A Study of The National Inpatient Sample.

BACKGROUND: In an unprecedented era of soaring healthcare costs, payers and providers alike have started to place increased importance on measuring the quality of surgical procedures as a surrogate for operative success. One metric used is the length of hospital stay (LOS) during index admission. For the treatment of unruptured cerebral aneurysms, the determinants of extended length of stay are relatively unknown. The aim of this study was to identify the patient- and hospital-level factors associated with extended LOS following treatment for unruptured cerebral aneurysms. METHODS: The National Inpatient Sample years 2010 - 2014 was queried. Adults (≥18 years) with unruptured aneurysms undergoing either clipping or coiling were selected using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Extended LOS was defined as greater than 75th percentile for the entire cohort (>5 days). Weighted patient demographics, comorbidities, complications, LOS, disposition and total cost were recorded. Multivariate logistic regression was used to determine the odds ratio for risk-adjusted extended LOS. The primary outcome was the degree which patient comorbidities or postoperative complications correlated with extended LOS. RESULTS: A total of 46,880 patients were identified for which 9,774 (20.8%) patients had extended LOS (Normal LOS: 37,106; Extended LOS: 9,774). Patients in the extended LOS cohort presented with a greater number of comorbidities compared to the normal LOS cohort. A greater proportion of the normal LOS cohort was coiled (Normal LOS: 63.0% vs. Extended LOS: 33.5%, P<0.001), while more patients in the extended LOS cohort were clipped (Normal LOS: 37.0% vs. Extended LOS: 66.5%, P<0.001). The overall complication rate was higher in the extended LOS cohort (Normal LOS: 7.3% vs. Extended LOS: 43.8%, P<0.001). On average, the extended LOS cohort incurred a total cost nearly twice as large (Normal LOS: $26,050 ± 13,430 vs. Extended LOS: $52,195 ± 37,252, P<0.001) and had more patients encounter non-routine discharges (Normal LOS: 8.5% vs. Extended LOS: 52.5%, P<0.001) compared to the normal LOS cohort. On weighted multivariate logistic regression, multiple patient-specific factors were associated with extended LOS. These included demographics, preadmission comorbidities, choice of procedure, and inpatient complications. The odds ratio for extended LOS was 5.14 (95% CI, 4.30 - 6.14) for patients with 1 complication and 19.58 (95% CI, 15.75 - 24.34) for patients with > 1 complication. CONCLUSIONS: Our study demonstrates that extended LOS after treatment of unruptured aneurysms is influenced by a number of patient-level factors including demographics, preadmission comorbidities, type of aneurysm treatment (open surgical versus endovascular), and, importantly, inpatient complications. A better understanding of these independent predictors of prolonged length of hospital stay may help to improve patient outcomes and decrease overall healthcare costs.

Risk of Radiation-Induced Cancer From Computed Tomography Angiography Use in Imaging Surveillance for Unruptured Cerebral Aneurysms.

Background and Purpose- Although computed tomography angiography (CTA) is an excellent, noninvasive imaging modality for surveillance of intracranial aneurysms, radiation concerns have been cited to restrict its use in surveillance imaging. The goal of this study was to estimate distributions of radiation-induced central nervous system cancer incidence from CTA surveillance for intracranial aneurysms, and the impact of frequency and duration of surveillance imaging using follow-up CTAs. Methods- Simulation-modeling approach was performed using data on CTA associated radiation risk. We used the Radiation Risk Assessment Tool, based on the data using the BEIR VII report (BEIR VII). Each CTA was assigned as a separate exposure event. Men and women, respectively, starting surveillance imaging at 30, 40, and 50 years and receiving annual CTAs were considered as separate subgroups. As a comparison, we also calculated the radiation-induced cancer risk in the same groups of patients but receiving CTAs every 2 and 5 years, respectively. Results- CTA-associated excess cancer risk per exposure increases relatively more rapidly with the first 10 exposures and plateaus after the 44th exposure. On average, per CTA incurs ≈0.0026% in excess lifetime cancer risk. Receiving CTA follow-up at a younger age, more frequent follow-up, longer surveillance period, and men are the major factors contributing to an elevated excess lifetime risk. In the highest risk group, male patient receiving annual CTA follow-ups from the age of 30 years, the excess lifetime risk is 0.115% at the age of 81 years. Conclusions- Radiation-induced brain cancer incidence associated with unruptured intracranial aneurysm surveillance strategies using CTA is low relative to the risk for aneurysmal rupture. Further cost-effectiveness/utility analyses might help assess this risk in the context of aneurysmal ruptures prevented by surveillance imaging.

Cost-Effectiveness of Computed Tomography Angiography in Management of Tiny Unruptured Intracranial Aneurysms in the United States.

Background and Purpose- Our study aims to evaluate the cost-effectiveness of computed tomography angiography (CTA) for surveillance of tiny unruptured intracranial aneurysms and the impact of CTA radiation-induced brain tumor on the overall effectiveness of CTA. Methods- A Markov decision model was constructed from a societal perspective starting with patients 30-, 40-, or 50-year-old, with incidental detection of unruptured intracranial aneurysm ≤3 mm and no prior history of subarachnoid hemorrhage. Five different management strategies were assessed (1) annual CTA surveillance, (2) biennial CTA, (3) CTA follow-up every 5 years, (4) coiling and subsequent magnetic resonance imaging follow-up, and (5) annual CTA surveillance for the first 2 years, followed by every 5-year CTA follow-up. Probabilistic, 1-way, and 2-way sensitivity analyses were performed. Results- The base case calculation shows every 5-year CTA follow-up to be the most cost-effective strategy, and the conclusion remains robust in probabilistic sensitivity analysis. It remains the dominant strategy when the annual rupture risk of nongrowing unruptured intracranial aneurysms is smaller than 2.66% or the rupture risk in growing aneurysms is <57.4%. The radiation-induced brain cancer risk is relatively low, and sensitivity analysis shows that the radiation-induced cancer risk does not influence the conclusions unless the risk exceeds 663-fold of the base case values. Conclusions- Given the current literature, every 5-year CTA imaging follow-up is the cost-effective strategy in patients with aneurysms ≤3 mm, resulting in better health outcomes and lower healthcare spending. Patients with aneurysms at high risk of rupture might need more aggressive management.

Comparative Effectiveness of Endovascular Thrombectomy in Elderly Stroke Patients.

Background and Purpose- Strokes in patients aged ≥80 years are common, and advanced age is associated with relatively poor poststroke functional outcome. The current guidelines do not recommend an upper age limit for endovascular thrombectomy (EVT). The purpose of this study is to evaluate the effectiveness of EVT in acute stroke because of large vessel occlusion for elderly patients >age 80 years. Methods- A Markov decision analytic model was constructed from a societal perspective to evaluate health outcomes in terms of quality-adjusted life years (QALYs) after EVT for acute ischemic stroke because of large vessel occlusion in patients above age 80 years. Age-specific input parameters were obtained from the most recent/comprehensive literature. Good outcome was defined as a modified Rankin Scale score ≤2. Probabilistic, 1-way, and 2-way sensitivity analyses were performed for both healthy patients and patients with disability at baseline. Results- Base case calculation showed in functionally independent patients at baseline, intravenous thrombolysis (IVT) with tPA (tissue-type plasminogen activator) only to be the better strategy with 3.76 QALYs compared to 2.93 QALYs for patients undergoing EVT. The difference in outcome is 0.83 QALY (equivalent to 303 days of life in perfect health). For patients with baseline disability, IVT only yields a utility of 1.92 QALYs and EVT yields a utility of 1.65 QALYs. The difference is 0.27 QALYs (equivalent to 99 days of life in perfect health). Multiple sensitivity analyses showed that the effectiveness of EVT is significantly determined by the morbidity and mortality after both IVT and EVT strategies, respectively. Conclusions- Our study demonstrates the impact of relevant factors on the effectiveness of EVT in patients above 80 years of age. Morbidity and mortality after both IVT and EVT strategies significantly influence the outcomes in both healthy and disabled patients at baseline. Better identification of patients not benefiting from IVT would optimize the selective use of EVT thereby improving its effectiveness.

Intensive Blood Pressure Reduction and Perihematomal Edema Expansion in Deep Intracerebral Hemorrhage.

Background and Purpose- It is unknown whether blood pressure (BP) reduction influences secondary brain injury in spontaneous intracerebral hemorrhage (ICH). We tested the hypothesis that intensive BP reduction is associated with decreased perihematomal edema expansion rate (PHER) in deep ICH. Methods- We performed an exploratory analysis of the ATACH-2 randomized trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2). Patients with deep, supratentorial ICH were included. PHER was calculated as the difference in perihematomal edema volume between baseline and 24-hour computed tomography scans divided by hours between scans. We used regression analyses to determine whether intensive BP reduction was associated with PHER and if PHER was associated with poor outcome (3-month modified Rankin Scale score 4-6). We then used interaction analyses to test whether specific deep location (basal ganglia versus thalamus) modified these associations. Results- Among 1000 patients enrolled in ATACH-2, 870 (87%) had supratentorial, deep ICH. Of these, 780 (90%) had neuroimaging data (336 thalamic and 444 basal ganglia hemorrhages). Baseline characteristics of the treatment groups remained balanced (P>0.2). Intensive BP reduction was associated with a decrease in PHER in univariable (ß= -0.15; 95% CI, -0.26 to -0.05; P=0.007) and multivariable (ß=-0.12; 95% CI, -0.21 to -0.02; P=0.03) analyses. PHER was not independently associated with outcome in all deep ICH (odds ratio, 1.14; 95% CI, 0.93-1.41; P=0.20), but this association was modified by the specific deep location involved (multivariable interaction P=0.02); in adjusted analyses, PHER was associated with poor outcome in basal ganglia (odds ratio, 1.42; 1.05-1.97; P=0.03) but not thalamic (odds ratio, 1.02; 95% CI, 0.74-1.40; P=0.89) ICH. Conclusions- Intensive BP reduction was associated with decreased 24-hour PHER in deep ICH. PHER was not independently associated with outcome in all deep ICH but was associated with poor outcome in basal ganglia ICH. PHER may be a clinically relevant end point for clinical trials in basal ganglia ICH.

MR Angiography Screening and Surveillance for Intracranial Aneurysms in Autosomal Dominant Polycystic Kidney Disease: A Cost-effectiveness Analysis.

Background Autosomal dominant polycystic kidney disease (ADPKD) affects one in 400 to one in 1000 individuals; 10%-11% of these individuals have intracranial aneurysms. The frequency and patterns of screening for intracranial aneurysms have not been defined. Purpose To evaluate different MR angiography screening and surveillance strategies for unruptured intracranial aneurysms in patients with ADPKD. Materials and Methods A Markov decision-analytic model was constructed accounting for both costs and outcomes from a societal perspective. Five different management strategies were evaluated: (a) no screening for intracranial aneurysm, (b) one-time screening with annual MR angiography follow-up in patients with intracranial aneurysm, (c) MR angiographic screening every 5 years with endovascular treatment in detected intracranial aneurysm, (d) MR angiography screening every 5 years with annual MR angiography follow-up in patients with intracranial aneurysm, and (e) MR angiography screening every 5 years with biennial follow-up in patients with intracranial aneurysm. One-way, two-way, and probabilistic sensitivity analyses were performed. Results Base case calculation shows that MR angiography screening of patients with ADPKD every 5 years and annual follow-up in patients with detected intracranial aneurysm is the optimal strategy (cost, $19 839; utility, 25.86 quality-adjusted life years), which becomes more favorable as the life expectancy increases beyond 6 years. The conclusion remains robust in probabilistic and one-way sensitivity analyses. When the prevalence of intracranial aneurysms is greater than 10%, annual rupture risk is 0.35%-2.5%, and the rate of de novo aneurysm detection is lower than 1.8%, MR angiography screening every 5 years with annual MR angiography follow-up is the favorable strategy. Conclusion Screening for intracranial aneurysms with MR angiography in patients with autosomal dominant polycystic kidney disease is cost-effective. Repeat screening every 5 years should be performed after a negative initial study. Annual surveillance MR angiography is optimal in patients with detected, incidental intracranial aneurysm, and treatment may be considered in patients with growing, high-risk aneurysms. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Anzai in this issue.

Management of Unruptured Intracranial Aneurysms in Older Adults: A Cost-effectiveness Analysis.

Background Unruptured intracranial aneurysms (UIAs) are relatively common and are being increasingly diagnosed, with a significant proportion in older patients (˃ 65 years old). Serial imaging is often performed to assess change in size or morphology of UIAs since growing aneurysms are known to be at high risk for rupture. However, the frequency and duration of surveillance imaging have not been established. Purpose To evaluate the cost-effectiveness of routine treatment (aneurysm coil placement) versus four different strategies for imaging surveillance of UIAs in adults older than 65 years. Materials and Methods A Markov decision-analytic model was constructed from a societal perspective. Age-dependent input parameters were obtained from published literature. Analysis included adults older than 65 years, with incidental detection of UIA and no prior history of subarachnoid hemorrhage. Five different management strategies for UIAs in older adults were evaluated: (a) annual MR angiography, (b) biennial MR angiography, (c) MR angiography every 5 years, (d) coil placement and follow-up, and (e) limited MR angiography follow-up for the first 2 years after detection only. Outcomes were assessed in terms of quality-adjusted life-years (QALYs). Probabilistic, one-way, and two-way sensitivity analyses were performed. Results Imaging follow-up for the first 2 years after detection is the most cost-effective strategy (cost = $24 572, effectiveness = 13.73 QALYs), showing the lowest cost and highest effectiveness. The conclusion remains robust in probabilistic and one-way sensitivity analyses. Time-limited imaging follow-up remains the optimal strategy when the annual growth rate and rupture risk of growing aneurysms are varied. If annual rupture risk of nongrowing aneurysms is greater than 7.1%, coil placement should be performed directly. Conclusion Routine preventive treatment or periodic, indefinite imaging follow-up is not a cost-effective strategy in all adults older than 65 years with unruptured intracranial aneurysms. More aggressive management strategies should be reserved for patients with high risk of rupture, such as those with aneurysms larger than 7 mm and those with aneurysms in the posterior circulation. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Cloft in this issue.

A Qualitative Study of Risks Related to Interhospital Transfer of Patients with Nontraumatic Intracranial Hemorrhage.

GOAL: Interhospital transfer (IHT) facilitates access to specialized neurocritical care but may also introduce unique risk. Our goal was to describe providers' perceptions of safety threats during IHT for patients with nontraumatic intracranial hemorrhage. MATERIALS AND METHODS: We employed qualitative, semi-structured interviews at an academic medical center receiving critically-ill neurologic transfers, and 5 referring hospitals. Interviewees included physicians, nurses, and allied health professionals with experience caring for patients transferred between hospitals for nontraumatic intracranial hemorrhage. Interviews continued until data saturation was reached. Coding occurred concurrently with interviews. Analysis was inductive, using the constant comparative method. FINDINGS: The predominant impediments to safe, high-quality neurocritical care transitions between hospitals are insufficient communication, gaps in clinical practice, and lack of IHT structure. Insufficient communication highlights the unique communication challenges specific to IHT, which overlay and compound known intrahospital communication barriers. Gaps in clinical practice revolve primarily around the provision of neurocritical care for this patient population, often subject to resource availability, by receiving hospital emergency medicine providers. Lack of structure outlines providers' questions that emerge when institutions fail to identify process channels, expectations, and accountability during complex neurocritical care transitions. CONCLUSIONS: The predominant impediments to safe, high-quality neurocritical care transitions between hospitals are insufficient communication, gaps in clinical practice, and lack of IHT structure. These themes serve as fundamental targets for quality improvement initiatives. To our knowledge, this is the first description of challenges to quality and safety in high-risk neurocritical care transitions through clinicians' voices.

Growth and Rupture Risk of Small Unruptured Intracranial Aneurysms: A Systematic Review.

BACKGROUND: Small unruptured intracranial aneurysms (UIAs) are increasingly diagnosed. Management depends on growth and rupture risks, which may vary by aneurysm size. PURPOSE: To summarize evidence about the growth and rupture risk of UIAs 7 mm and smaller and to explore differences in growth and rupture risks of very small (≤3 mm) and small (≤5 mm) aneurysms. DATA SOURCES: MEDLINE, EMBASE, Scopus, and the Cochrane Library from inception to 2017 (with no language restrictions). STUDY SELECTION: Published case series and observational studies that reported natural history data on UIAs 7 mm and smaller. DATA EXTRACTION: 2 reviewers abstracted study information, evaluated study quality, and graded strength of evidence. DATA SYNTHESIS: Of 26 studies, 5, 10, and 8 described the growth rate of aneurysms 3 mm and smaller, 5 mm and smaller, and 7 mm and smaller, respectively, whereas rupture rates were reported in 7, 11, and 13 studies for aneurysms 3 mm and smaller, 5 mm and smaller, and 7 mm and smaller, respectively. The annualized growth rate was less than 3% in all but 1 study for all 3 size categories. The annualized rupture rate was 0%, less than 0.5%, and less than 1% for the 3 size categories, respectively. Strength of evidence was very low quality for growth rates and low quality for rupture rates. LIMITATION: Heterogeneous definitions of growth; heterogeneous and selective treatment and follow-up methods, particularly in high-risk patients. CONCLUSION: Poor-quality evidence suggests that small UIAs have low growth and rupture rates and very small UIAs have little or no risk for rupture. PRIMARY FUNDING SOURCE: None.