Net water uptake as a predictive neuroimaging marker for acute ischemic stroke outcomes: a meta-analysis.

OBJECTIVE: To assess the role of net water uptake (NWU) in predicting outcomes in acute ischemic stroke (AIS) patients. METHODS: A systematic review and meta-analysis were performed, adhering to established guidelines. The search covered PubMed, Scopus, Web of Science, and Embase databases until July 1, 2023. Eligible studies reporting quantitative ischemic lesion NWU in admission CT scans of AIS patients, stratified based on outcomes, were included. Data analysis was performed using R software version 4.2.1. RESULTS: Incorporating 17 original studies with 2217 AIS patients, NWU was significantly higher in patients with poor outcomes compared to those with good outcomes (difference of medians: 5.06, 95% CI: 3.00-7.13, p < 0.001). Despite excluding one outlier study, considerable heterogeneity persisted among the included studies (I2 = 90.8%). The meta-regression and subgroup meta-analyses demonstrated significantly higher NWU in patients with poor functional outcome, as assessed by modified Rankin Scale (difference of medians: 3.83, 95% CI: 1.98-5.68, p < 0.001, I2 = 72.9%), malignant edema/infarct (difference of medians: 8.30, 95% CI: 4.01-12.58, p < 0.001, I2 = 95.6%), and intracranial hemorrhage (difference of medians: 5.43, 95% CI: 0.44-10.43, p = 0.03, I2 = 91.1%). CONCLUSION: NWU on admission CT scans shows promise as a predictive marker for outcomes in AIS patients. Prospective, multicenter trials with standardized, automated NWU measurement are crucial for robustly predicting diverse clinical outcomes. CLINICAL RELEVANCE STATEMENT: The potential of net water uptake as a biomarker for predicting outcomes in acute ischemic stroke patients holds significant promise. Further validation through additional research could lead to its integration into clinical practice, potentially improving the accuracy of clinical decision-making and allowing for the development of more precise patient care strategies. KEY POINTS: • Net water uptake, a CT-based biomarker, quantifies early brain edema after acute ischemic stroke. • Net water uptake is significantly higher in poor outcome acute ischemic stroke patients. • Net water uptake on CT scans holds promise in predicting diverse acute ischemic stroke outcomes.

High thrombin-activatable fibrinolysis inhibitor expression in thrombi from stroke patients in elevated estrogen states.

BACKGROUND: The risk of acute ischemic stroke (AIS) associated with high estrogen states, including pregnant patients and those using oral contraceptives, has been well documented. We described the histological composition of thrombi collected in these cases. METHODS: From a prospective tissue registry (STRIP registry) of thrombi retrieved during mechanical thrombectomy for AIS, we identified 5 patients with high estrogen states: 1 post-partum patient, 1 undergoing hormone replacement therapy and 3 consuming oral contraceptive pills. Five male control patients were randomly chosen matched by age. Immunohistochemistry for CD42b (platelets), von Willebrand factor (vWF), thrombin-activatable fibrinolysis inhibitor (TAFI), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) was performed. Expression was quantified using Orbit Image Software. Student's t-test was performed as appropriate. RESULTS: Mean TAFI content for the high estrogen state group was higher than controls (25.6 ± 11.9% versus 9.3 ± 9.0%, p = 0.043*). Mean platelet content for the high estrogen state group was lower than controls (41.7 ± 10.6% versus 61.8 ± 12.9%, p = 0.029*). No significant difference was found in vWF, fibrinogen and PAI-1 expression. Mean time to recanalize was higher in the high estrogen state group compared to the control group (57.8 ± 27.6 versus 22.6 ± 11.4 min, p = 0.0351*). The mean number of passes required was higher in the high estrogen group compared to controls 4.6 versus 1.2, p = 0.0261*). CONCLUSIONS: TAFI expression, a powerful driver of thrombosis, was significantly higher in stroke thrombi among patients with high estrogen states compared to controls.

Common Design and Data Elements Reported on Idiopathic Intracranial Hypertension Trials: A Systematic Review.

BACKGROUND: There are an increasing number of controlled clinical trials and prospective studies, ongoing and recently completed, regarding management options for idiopathic intracranial hypertension (IIH). We present a Common Design and Data Element (CDDE) analysis of controlled and prospective IIH studies with the aim of aligning essential design and recommending data elements in future trials and enhancing data synthesis potential in IIH trials. METHODS: We used PubMed and ClinicalTrials.gov to screen for ongoing and published trials assessing treatment modalities in people with IIH. After our search, we used the Nested Knowledge AutoLit platform to extract pertinent information regarding each study. We examined outputs from each study and synthesized the data elements to determine the degree of homogeneity between studies. RESULTS: The most CDDE for inclusion criteria was the modified Dandy criteria for diagnosis of IIH, used in 9/14 studies (64%). The most CDDE for outcomes was change in visual function, reported in 12/14 studies (86%). Evaluation of surgical procedures (venous sinus stenting, cerebrospinal fluid shunt placement, and others) was more common, seen in 9/14 studies (64%) as compared with interventions with medical therapy 6/14 (43%). CONCLUSIONS: Although all studies have similar focus to improve patient care, there was a high degree of inconsistency among studies regarding inclusion criteria, exclusion criteria, and outcomes measures. Furthermore, studies used different time frames to assess outcome data elements. This heterogeneity will make it difficult to achieve a consistent standard, and thus, making secondary analyses and meta-analyses less effective in the future. Consensus on design of trials is an unmet research need for IIH.

Safety and efficacy profile of off-label use of the Pipeline Embolization Device: A systematic review and meta-analysis.

OBJECTIVE: The off-label utilization of the Pipeline Embolization Device (PED) is a common practice in numerous medical centers globally. Therefore, we conducted a systematic review and meta-analysis to evaluate the overall outcomes of this off-label usage of PEDs. METHODS: PubMed, Web of Science, Ovid Medline, Ovid Embase, and Scopus were searched up to February 2023 using the Nested Knowledge platform to identify studies assessing the off-label use of PEDs. Any use of PED outside of the FDA-approved indication granted in 2018 is considered off-label use. Overall angiographic occlusion rates, ischemic and hemorrhagic complications, mortality, retreatment rates, and favorable clinic outcomes were included. Statistical analyses were performed to compare the overall outcome rates of anterior cerebral artery(ACA) vs. middle cerebral artery(MCA) and anterior vs posterior circulation subgroups. RESULTS: We included 26 studies involving a total of 1,408 patients. The overall rate of complete occlusion was 80.3 % (95 % CI= 76.0-84.1). Subgroup analysis demonstrated a statistically significant difference in the rate of complete occlusion between anterior circulation (78.9 %) and posterior circulation (69.2 %) (p value=0.02). The rate of good clinical outcomes was 92.8 % (95 % CI= 88.8-95.4). The mortality rate was 1.4 % (95 % CI= 0.5-2.7). The overall rate of ischemic complications was 9.5 % (95 % CI= 7.7-11.6), with a comparable difference between anterior circulation (7.7 %) and posterior circulation (12.8 %) (p value=0.07). There was no statistically significant difference in MCA vs ACA subgroups in all parameters. CONCLUSIONS: Off-label use of PEDs can be a safe and effective treatment option for intracranial aneurysms. However, there is a need for more prospective, high-quality, non-industry-funded registry studies and randomized trials to test the efficacy and safety of off-label usage of PEDs and to expand its indications.

Machine learning prediction of hospital discharge disposition for inpatients with acute ischemic stroke following mechanical thrombectomy in the United States.

BACKGROUND AND PURPOSE: Predicting patient recovery and discharge disposition following mechanical thrombectomy remains a challenge in patients with ischemic stroke. Machine learning offers a promising prognostication approach assisting in personalized post-thrombectomy care plans and resource allocation. As a large national database, National Inpatient Sample (NIS), contain valuable insights amenable to data-mining. The study aimed to develop and evaluate ML models predicting hospital discharge disposition with a focus on demographic, socioeconomic and hospital characteristics. MATERIALS AND METHODS: The NIS dataset (2006-2019) was used, including 4956 patients diagnosed with ischemic stroke who underwent thrombectomy. Demographics, hospital characteristics, and Elixhauser comorbidity indices were recorded. Feature extraction, processing, and selection were performed using Python, with Maximum Relevance - Minimum Redundancy (MRMR) applied for dimensionality reduction. ML models were developed and benchmarked prior to interpretation of the best model using Shapley Additive exPlanations (SHAP). RESULTS: The multilayer perceptron model outperformed others and achieved an AUROC of 0.81, accuracy of 77 %, F1-score of 0.48, precision of 0.64, and recall of 0.54. SHAP analysis identified the most important features for predicting discharge disposition as dysphagia and dysarthria, NIHSS, age, primary payer (Medicare), cerebral edema, fluid and electrolyte disorders, complicated hypertension, primary payer (private insurance), intracranial hemorrhage, and thrombectomy alone. CONCLUSION: Machine learning modeling of NIS database shows potential in predicting hospital discharge disposition for inpatients with acute ischemic stroke following mechanical thrombectomy in the NIS database. Insights gained from SHAP interpretation can inform targeted interventions and care plans, ultimately enhancing patient outcomes and resource allocation.

Endovascular outcomes for anterior choroidal artery aneurysms: systematic review and meta-analysis.

BACKGROUND: Anterior choroidal artery (AchoA) aneurysms are relatively rare compared to other types of aneurysms. However, the occurrence of transient or permanent occlusion of the choroidal artery during endovascular or surgical treatment is an uncommon but potentially serious complication. In this study, we aim to investigate the safety and efficacy profile of endovascular treatment (EVT) for AchoA aneurysms. METHODS: The primary outcome of interest was angiographic and clinical outcomes. Secondary outcome variables transient and permanent ischemic complications, symptomatic choroidal artery occlusion and retreatment rates. A random-effects model was used to calculate prevalence rates and their corresponding 95 % confidence intervals (CI), and subgroup analyses were performed to assess the complication rates for Type 1(arterial type, directly arising from ICA) and Type 2(neck type, arising from AchoA branch)) AchoA aneurysms, ruptured vs non-ruptured and for flow diverter (FD) treatment versus coiling. RESULTS: Our study included 10 studies with 416 patients with 430 AchoA aneurysms. The overall good clinical outcome rate (mRS score 0-2) is 94.5 % with a retreatment rate of 2.0 %. A subgroup analysis showed no statistical difference between coiling(75.3 %) and flow diverter(80.9 %) treatment in terms of complete occlusion(p-value:0.62). Overall permanent complication rate is 1.4 % (p-value:0.54) and transient ischemic complications rate is 4.2 %(p-value:0.61). Symptomatic choroidal artery occlusion rate is 0.8 %(p-value:0.51)Type 2 AchoA aneurysms had a significantly higher complication rate of 9.8 % (p-value<0.05) compared to Type 1 aneurysms. Unruptured aneurysms have significantly better clinical outcomes than ruptured aneurysms(OR: 0.11; [0.02;0.5], p-value:<0.05) CONCLUSION: Endovascular treatment of AchoA aneurysms demonstrated positive clinical results, with low rates of retreatment and complications. Coiling and flow diverters proved similar outcomes in achieving aneurysm occlusion. Ruptured aneurysms have lower good clinical outcomes comparing to unruptured aneurysms. Type 2 AchoA aneurysms had a higher risk of complications compared to Type 1.

The impact of pre-stroke metformin use on clinical outcomes after acute ischemic stroke: A systematic review and meta-analysis.

OBJECTIVES: Stroke is a leading cause of mortality and disability globally, with limited treatment options available for acute ischemic stroke (AIS) patients. Type 2 diabetes mellitus (T2DM) is not only widespread but also a known risk factor for stroke. Our meta-analysis aims to assess the influence of pre-stroke metformin use on the clinical outcomes in AIS patients with T2DM. MATERIALS AND METHODS: We conducted this study following PRISMA guidelines, searching the following databases: Medline, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials up to February 29, 2024. All studies providing separate data on AIS patients using metformin were included, and statistical analysis was conducted using R software to pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). RESULTS: Out of 1051 studies, 7 met the inclusion criteria for our meta-analysis with a total of 11589 diabetic patients, including 5445 patients taking metformin and 6144 diabetic patients in the non-metformin group. Compared to the non-metformin group, the metformin group had a significantly higher rate of mRS 0-2 score at discharge (OR 1.56; 95% CI 1.25:1.95; p=< 0.01) and a lower rate of 90-day mortality (OR 0.51; 95% CI 0.42:0.61; p=< 0.01), with no significant difference in sICH (OR 0.88; 95% CI 0.47:1.64; p= 0.68) between the two groups. CONCLUSIONS: Our meta-analysis demonstrated that pre-stroke metformin use is associated with higher functional independence and lower mortality in AIS patients with T2DM.

Development of Parkinson Disease and Its Relationship with Incidentally Discovered White Matter Disease and Covert Brain Infarction in a Real-World Cohort.

OBJECTIVE: This study aimed to examine the relationship between covert cerebrovascular disease, comprised of covert brain infarction and white matter disease, discovered incidentally in routine care, and subsequent Parkinson disease. METHODS: Patients were ≥50 years and received neuroimaging for non-stroke indications in the Kaiser Permanente Southern California system from 2009 to 2019. Natural language processing identified incidentally discovered covert brain infarction and white matter disease and classified white matter disease severity. The Parkinson disease outcome was defined as 2 ICD diagnosis codes. RESULTS: 230,062 patients were included (median follow-up 3.72 years). A total of 1,941 Parkinson disease cases were identified (median time-to-event 2.35 years). Natural language processing identified covert cerebrovascular disease in 70,592 (30.7%) patients, 10,622 (4.6%) with covert brain infarction and 65,814 (28.6%) with white matter disease. After adjustment for known risk factors, white matter disease was associated with Parkinson disease (hazard ratio 1.67 [95%CI, 1.44, 1.93] for patients <70 years and 1.33 [1.18, 1.50] for those ≥70 years). Greater severity of white matter disease was associated with increased incidence of Parkinson disease(/1,000 person-years), from 1.52 (1.43, 1.61) in patients without white matter disease to 4.90 (3.86, 6.13) in those with severe disease. Findings were robust when more specific definitions of Parkinson disease were used. Covert brain infarction was not associated with Parkinson disease (adjusted hazard ratio = 1.05 [0.88, 1.24]). INTERPRETATION: Incidentally discovered white matter disease was associated with subsequent Parkinson disease, an association strengthened with younger age and increased white matter disease severity. Incidentally discovered covert brain infarction did not appear to be associated with subsequent Parkinson disease. ANN NEUROL 2022;92:620-630.

Mortality among older adults with osteoporotic vertebral fracture.

We evaluated whether older adults who received kyphoplasty had reduced risk of mortality compared to those who did not. In unmatched analyses, those receiving kyphoplasty were at reduced risk of death but after matching on age and medical complications, patients who received kyphoplasty were at increased risk of death. PURPOSE: In previous observational studies, kyphoplasty for treatment of osteoporotic vertebral fractures has been associated with decreased mortality compared to conservative management. The purpose of this research was to determine whether older adults who received kyphoplasty had reduced risk of mortality compared to matched patients who did not. METHODS: Retrospective cohort study of US Medicare enrollees with osteoporotic vertebral fractures between 2017-2019 comparing patients who underwent kyphoplasty to those who did not. We identified 2 control groups a priori: 1) non-augmented patients who met inclusion criteria (group 1); 2) propensity-matched patients on demographic and clinical variables (group 2). We then identified additional control groups using matching for medical complications (group 3) and age + comorbidities (group 4). We calculated hazard ratios (HRs) and 95% confidence intervals (95% CIs) associated with mortality. RESULTS: A total of 235,317 patients (mean (± standard deviation) age 81.1 ± 8.3 years; 85.8% female) were analyzed. In the primary analyses, those who received kyphoplasty were at reduced risk of death compared to those who did not: adjusted HR (95% CI) in group 1 = 0.84 (0.82, 0.87); and in group 2 = 0.88 (0.85, 0.91). However, in post hoc analyses, patients who received kyphoplasty were at increased risk of death: adjusted HR (95% CI) in group 3 = 1.32 (1.25, 1.41) and 1.81 (1.58, 2.09) in group 4. CONCLUSION: An apparent benefit of kyphoplasty on mortality among patients with vertebral fractures was not present after rigorous propensity matching, illustrating the importance of comparing similar individuals when evaluating observational data.

The Effect of Mechanical Thrombectomy on the Incidence of Poststroke Cognitive Impairment: A Systematic Review of Inhomogeneous Literature.

INTRODUCTION: The aim of this study was to evaluate the effect of mechanical thrombectomy (MT) on the incidence of poststroke cognitive impairment (PSCI) in anterior circulation stroke. METHODS: Literature research was performed on PubMed/OVID/Cochrane CENTRAL for studies published in 2015-2022. A review of the references of the included papers was performed for further eligible articles. Clinical characteristics, NIHSS, dementia tests, and outcomes were recorded. The exclusion criteria were nonhuman and non-English. Studies qualities were assessed with MINORS/RoB2 and GRADE. A meta-analysis was performed using the standardized mean difference (Cohen's d) to measure effect size. RESULTS: Four studies were included in the systematic review after screening 749 articles. No significant differences were found for age and gender (years: 66.70 ± 11.14 vs. 67.59 ± 10.11, p = 0.37; male 53.8% vs. 56.4%, p = 0.57). MT patients had a more severe stroke than that of the control group (NIHSS: 14.70 ± 4.31 vs. 11.17 ± 4.12; p < 0.0001). The control group consisted of medical therapy-alone patients in all studies. I2 was 76.95%, and Q was 43.4%. MT patients have better performance in overall cognition (d = 0.33 [0.074-0.58]) and in several cognitive domains than in the control group (TMT-A, d = 0.37 [0.04-0.70]; TMT-B, d = 0.35 [0.12-0.58]; digit span test [backward], d = 0.61 [0.18-1.06]; colored progressive matrices, d = 0.48 [0.05-0.91]; Stroop test [word reading], d = 0.60 [0.17-1.03]; color naming, d = 0.51 [0.08-0.94]; Rey-Osterrieth Complex Figure [immediate recall], d = 0.79 [0.35-1.23]; Rey Auditory Verbal Learning Test [immediate recall], d = 0.79 [0.36-1.23]; delayed recall, d = 0.46 [0.035-0.89]; and MOCA, d = 0.46 [-0.04 to 0.96]). Medical therapy patients had a higher score in coping strategy than MT patients (COPE-28 acceptance, d = -1.00 [-1.53 to -0.48]). CONCLUSIONS: The incidence of PSCI is lower in MT patients than in the control group.

Stratifying future stroke risk with incidentally-discovered white matter disease severity and covert brain infarct site.

BACKGROUND: Covert cerebrovascular disease (CCD) includes white matter disease (WMD) and covert brain infarction (CBI). Incidentally-discovered CCD is associated with increased risk of subsequent symptomatic stroke. However, it is unknown whether the severity of WMD or the location of CBI predicts risk. OBJECTIVES: To examine the association of incidentally-discovered WMD severity and CBI location with risk of subsequent symptomatic stroke. METHOD: This retrospective cohort study includes patients 50 years old in the Kaiser Permanente Southern California health system who received neuroimaging for a non-stroke indication between 2009-2019. Incidental CBI and WMD were identified via natural language processing of the neuroimage report, and WMD severity was classified into grades. RESULTS: 261,960 patients received neuroimaging; 78,555 (30.0%) were identified to have incidental WMD, and 12,857 (4.9%) to have incidental CBI. Increasing WMD severity is associated with increased incidence rate of future stroke. However, the stroke incidence rate in CT-identified WMD is higher at each level of severity compared to rates in MRI-identified WMD. Patients with mild WMD via CT have a stroke incidence rate of 24.9 per 1,000 person-years, similar to that of patients with severe WMD via MRI. Among incidentally-discovered CBI patients with a determined CBI location, 97.9% are subcortical rather than cortical infarcts. CBI confers a similar risk of future stroke, whether cortical or subcortical, or whether MRI- or CT-detected. CONCLUSIONS: Increasing severity of incidental WMD is associated with an increased risk of future symptomatic stroke, dependent on the imaging modality. Subcortical and cortical CBI conferred similar risks.

Stratifying Future Stroke Risk with Incidentally Discovered White Matter Disease Severity and Covert Brain Infarct Site.

BACKGROUND: Covert cerebrovascular disease (CCD) includes white matter disease (WMD) and covert brain infarction (CBI). Incidentally discovered CCD is associated with increased risk of subsequent symptomatic stroke. However, it is unknown whether the severity of WMD or the location of CBI predicts risk. OBJECTIVES: The aim of this study was to examine the association of incidentally discovered WMD severity and CBI location with risk of subsequent symptomatic stroke. METHOD: This retrospective cohort study includes patients aged ≥50 years old in the Kaiser Permanente Southern California health system who received neuroimaging for a nonstroke indication between 2009 and 2019. Incidental CBI and WMD were identified via natural language processing of the neuroimage report, and WMD severity was classified into grades. RESULTS: A total of 261,960 patients received neuroimaging; 78,555 patients (30.0%) were identified to have incidental WMD and 12,857 patients (4.9%) to have incidental CBI. Increasing WMD severity is associated with an increased incidence rate of future stroke. However, the stroke incidence rate in CT-identified WMD is higher at each level of severity compared to rates in MRI-identified WMD. Patients with mild WMD via CT have a stroke incidence rate of 24.9 per 1,000 person-years, similar to that of patients with severe WMD via MRI. Among incidentally discovered CBI patients with a determined CBI location, 97.9% are subcortical rather than cortical infarcts. CBI confers a similar risk of future stroke, whether cortical or subcortical or whether MRI- or CT-detected. CONCLUSIONS: Increasing severity of incidental WMD is associated with an increased risk of future symptomatic stroke, dependent on the imaging modality. Subcortical and cortical CBI conferred similar risks.

Off-Label Use of the 8-F Angio-Seal for Closure of Greater than 8-F Common Femoral Arterial Access: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the safety of >8-F access closures using 8-F Angio-Seal. MATERIALS AND METHODS: An electronic search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines using Web of Science, Embase, Scopus, and PubMed databases from inception until January 17, 2022. Actionable and nonactionable bleeding events were defined in conjugation with the Bleeding Academic Research Consortium definition. Prevalence rates with corresponding 95% CIs were calculated using R software version 4.2.2. Eight articles, with 422 patients, were included in the analysis. RESULTS: The overall groin adverse event rate was 5.92% (95% CI, 3.01-11.34). The most commonly reported adverse events were any bleeding (5.74%; 95% CI, 3.23-10.00) (nonactionable bleeding, 0.96% [95% CI, 0.10-8.30]; actionable bleeding, 2.30% [95% CI, 0.89-5.84]), pseudoaneurysm (1.18%; 95% CI, 0.49-2.81), and groin hematoma (1.28%; 95% CI, 0.23-6.79). The least commonly reported adverse events were device failure and vessel occlusion/stenosis, with rates 0.29% (95% CI, 0.01-7.41) and 0.45% (95% CI, 0.02-7.74), respectively. No studies recorded events regarding the following adverse events: mortality, infection, deep venous thrombosis, and retroperitoneal hematoma. Moreover, the results showed significant differences, based on the sheath size used, in actionable bleeding (P = .04) and the rate of need for surgical repair (P < .01). CONCLUSIONS: Common femoral artery access of >8-F can be effectively closed with the Angio-Seal with comparable outcomes to those of <8 F; however, larger access approaching 14 F is associated with a significant increase in morbidity. Further safety is needed, especially for the larger access sizes.

Metabolite signature in acute ischemic stroke thrombi: a systematic review.

Metabolites are reliable biomarkers for many diseases. However, their role in acute ischemic stroke (AIS) pathogenesis is not well understood. In this systematic review we aim to evaluate the current literature on the presence of metabolites in thrombi retrieved by mechanical thrombectomy from AIS patients. Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines, we searched OVID Medline, PubMed, OVID Embase, Scopus, and Web of Science until July 13, 2022. Metabolites lists were extracted, and pathway analysis was performed in MetaboAnalyst database. Four articles listing metabolites were included in this systematic review. D-Glucose, diacylglycerol, phytosphingosine, galabiosylceramide, glucosylceramide and 4-hydroxynonenal were reported to be associated with clots. Metabolomics data analysis showed that glycolysis, lactose, and sphingolipid metabolism pathways were enriched. In conclusion, results of the present study show that the thrombi niche has a glycolytic phenotype. Future studies should work to better understand the metabolic properties of AIS thrombi.

Long-term outcomes following pipeline embolization of unruptured aneurysms.

BACKGROUND: Flow diversion using the pipeline embolization device (PED) for unruptured aneurysms is associated with high occlusion and low morbidity and mortality. However, most reports have limited follow-up of 1-2 years. Therefore, we sought to report our outcomes after PED for unruptured aneurysms in patients with at least 5-years of follow-up. METHODS: Review of patients undergoing PED for unruptured aneurysms from 2009 to 2016. RESULTS: Overall, 135 patients with 138 aneurysms were included for analysis. Seventy-eight percent of aneurysms (n=107) over a median radiographic follow-up of 5.0 years underwent complete occlusion. Among aneurysms with at least 5-years of radiographic follow-up (n=71), 79% (n=56) achieved complete obliteration. No aneurysm recanalized after radiographic obliteration. Furthermore, over a median clinical follow-up period of 4.9 years, 84% of patients (n=115) self-reported mRS scores between 0 and 2. For patients with at least 5-years of clinical follow-up, 88% (n=61) reported mRS between 0 and 2. In total, 3% (n=4) of patients experienced a major, non-fatal neurologic complication related to the PED, 5% (n=7) of patients experienced a minor neurologic complication related to PED placement, and 2% (n=3) died from either delayed aneurysm rupture, delayed ipsilateral hemorrhage after PED placement, or delayed (9 months after treatment) neural compression after progressive thrombosis of a PED-treated dolichoectactic vertebrobasilar aneurysm. CONCLUSIONS: Treatment of unruptured aneurysms with the PED is associated with high rates of long-term angiographic occlusion and low, albeit clinically important, rates of major neurologic morbidity and mortality. Thus, flow diversion via PED placement is safe, effective, and durable.

First-pass effect in posterior acute ischemic stroke undergoing endovascular thrombectomy: A systematic review and meta-analysis.

OBJECTIVES: First-pass effect (FPE) has been shown to be a predictor of favorable clinical outcomes following endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) in the anterior circulation. Literature regarding FPE for posterior circulation AIS is sparse; we conducted a systematic review and meta-analysis to explore FPE in posterior circulation stroke undergoing EVT. MATERIALS AND METHODS: We conducted a systematic review of the English literature in PubMed, Embase, Scopus, and Web of Science. FPE was defined as thrombolysis in cerebral infarction (TICI) 2c-3 and modified FPE (mFPE) was defined as TICI 2b-3 in one pass. Definitions of non-FPE and non-mFPE varied among studies. The primary outcome of interest was modified Rankin Scale (mRS) 0-2. Secondary outcomes of interest were mRS 0-3, symptomatic intracranial hemorrhage (sICH), and mortality. We calculated odds ratios (OR) and corresponding 95% confidence intervals (CI). Heterogeneity was assessed with Q statistic and I2 test. RESULTS: Seven studies with 417 patients in the mFPE group, 942 in the non-mFPE group, 545 in the FPE group, and 1023 in the non-FPE group were included. Overall, FPE was associated with greater rates of 90-day mRS 0-2 (OR= 2.78, 95% CI= 2.11-3.65; P-value< 0.001) and mRS 0-3 (OR= 2.67, 95% CI= 1.98-3.60; P-value< 0.001); however, there was significant heterogeneity among studies for both mRS 0-2 (I2= 69%; P-value< 0.001) and mRS 0-3 (I2= 69%; P-value< 0.001). FPE and non-FPE were associated with similar rates of sICH (OR= 0.65, 95% CI= 0.40-1.07; P-value= 0.09), and no heterogeneity was observed (I2= 0%; P-value= 0.95). FPE was associated with lower rates of mortality (OR= 0.44, 95% CI= 0.33-0.58; P-value< 0.001), although heterogeneity was observed (I2= 58%; P-value= 0.01). CONCLUSIONS: FPE is associated with favorable clinical outcomes in patients undergoing EVT for posterior circulation AIS. Future studies should work to further quantify the impact of FPE on outcomes in the posterior circulation.

Differences between males and females following endovascular therapy for stroke: A systematic review and meta-analysis.

BACKGROUND: Endovascular therapy (EVT) represents the standard of care for eligible patients with acute ischemic stroke (AIS) and large vessel occlusion. To better understand differences in baseline characteristics and outcomes between males and females following EVT, we conducted a systematic review and meta-analysis. METHODS: We identified, using the Nested Knowledge AutoLit platform, prospective studies that reported 90-day outcomes in males and females treated with EVT for AIS. The primary outcome of interest was 90-day modified Rankin Scale (mRS) 0-2. Secondary outcome variables included mRS 0-1, symptomatic intracranial hemorrhage (sICH), thrombolysis in cerebral infarction (TICI) score 2b-3, and mortality. Using R software version 4.1.2, we calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). RESULTS: We included 10 studies with 10,209 patients. There was no difference between males and females in rate of mRS 0-2 (OR= 1.16; 95% CI= 0.87-1.56; P-value= 0.316); however, after removing outliers, males had higher rates of mRS 0-2 (OR= 1.40; 95% CI= 1.19-1.66; P-value< 0.001). Similar results were reported for mRS 0-1 (OR= 1.21; 95% CI= 0.93-1.56; P-value= 0.15), after removing outliers (OR= 1.32; 95% CI= 1.17-1.50; P-value< 0.001). There was no difference between males and females in rate of sICH (OR= 0.89; 95% CI= 0.74-1.08; P-value= 0.246), mortality (OR= 0.88; 95% CI= 0.74-1.05; P-value= 0.15), or TICI 2b-3 (OR= 1.19; 95% CI= 0.85-1.67; P-value= 0.309). CONCLUSIONS: Males tend to experience better outcomes following EVT for AIS, even in the setting of similar reperfusion. The mechanisms underlying this phenomenon remain unclear, and further research is warranted. EVT remains a safe and effective option for both males and females with AIS.

The diagnostic performance of artificial intelligence algorithms for identifying M2 segment middle cerebral artery occlusions: A systematic review and meta-analysis.

BACKGROUND: Artificial intelligence (AI)-based algorithms have been developed to facilitate rapid and accurate computed tomography angiography (CTA) assessment in proximal large vessel occlusion (LVO) acute ischemic stroke, including internal carotid artery and M1 occlusions. In clinical practice, however, the detection of medium vessel occlusion (MeVO) represents an ongoing diagnostic challenge in which the added value of AI remains unclear. PURPOSE: To assess the diagnostic performance of AI platforms for detecting M2 occlusions. METHODS: Studies that report the diagnostic performance of AI-based detection of M2 occlusions were screened, and sensitivity and specificity data were extracted using the semi-automated AutoLit software (Nested Knowledge, MN) platform. STATA (version 16 IC; Stata Corporation, College Station, Texas, USA) was used to conduct all analyses. RESULTS: Eight studies with a low risk of bias and significant heterogeneity were included in the quantitative and qualitative synthesis. The pooled estimates of sensitivity and specificity of AI platforms for M2 occlusion detection were 64% (95% CI, 53 to 74%) and 97% (95% CI, 84 to 100%), respectively. The area under the curve (AUC) in the SROC curve was 0.79 (95% CI, 0.74 to 0.83). CONCLUSION: The current performance of the AI-based algorithm makes it more suitable as an adjunctive confirmatory tool rather than as an independent one for M2 occlusions. With the rapid development of such algorithms, it is anticipated that newer generations will likely perform much better.

Neurologic Effects of Gadolinium Retention in the Brain after Gadolinium-based Contrast Agent Administration.

Background Concerns over the neurotoxic potential of retained gadolinium in brain tissues after intravenous gadolinium-based contrast agent (GBCA) administration have led to pronounced worldwide use changes, yet the clinical sequelae of gadolinium retention remain undefined. Purpose To assess clinical and neurologic effects and potential neurotoxicity of gadolinium retention in rats after administration of various GBCAs. Materials and Methods From March 2017 through July 2018, 183 male Wistar rats received 20 intravenous injections of 2.5 mmol per kilogram of body weight (80 human equivalent doses) of various GBCAs (gadodiamide, gadobenate, gadopentetate, gadoxetate, gadobutrol, gadoterate, and gadoteridol) or saline over 4 weeks. Rats were evaluated 6 and 34 weeks after injection with five behavioral tests, and inductively coupled plasma mass spectrometry, transmission electron microscopy, and histopathology were performed on urine, serum, cerebrospinal fluid (CSF), basal ganglia, dentate nucleus, and kidney samples. Dunnett post hoc test and Wilcoxon rank sum test were used to compare differences between treatment groups. Results No evidence of differences in any behavioral test was observed between GBCA-exposed rats and control animals at either 6 or 34 weeks (P = .08 to P = .99). Gadolinium concentrations in both neuroanatomic locations were higher in linear GBCA-exposed rats than macrocyclic GBCA-exposed rats at 6 and 34 weeks (P < .001). Gadolinium clearance over time varied among GBCAs, with gadobutrol having the largest clearance (median: 62% for basal ganglia, 70% for dentate) and gadodiamide having no substantial clearance. At 34 weeks, gadolinium was largely cleared from the CSF and serum of gadodiamide-, gadobenate-, gadoterate-, and gadobutrol-exposed rats, especially for the macrocyclic agents (range: 70%-98% removal for CSF, 34%-94% removal for serum), and was nearly completely removed from urine (range: 96%-99% removal). Transmission electron microscopy was used to detect gadolinium foci in linear GBCA-exposed brain tissue, but no histopathologic differences were observed for any GBCA. Conclusion In this rat model, no clinical evidence of neurotoxicity was observed after exposure to linear and macrocyclic gadolinium-based contrast agents at supradiagnostic doses. © RSNA, 2022 Online supplemental material is available for this article.

Histological composition of retrieved emboli in acute ischemic stroke is independent of pre-thrombectomy alteplase use.

BACKGROUND AND PURPOSE: Given recent evidence suggesting the clot composition may be associated with revascularization outcomes and stroke etiology, clot composition research has been a topic of growing interest. It is currently unclear what effect, if any, pre-thrombectomy thrombolysis has on clot composition. Understanding this association is important as it is a potential confounding variable in clot composition research. We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients who did and did not receive pre-treatment tPA to study the effect of tPA on clot composition. MATERIALS AND METHODS: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using Martius Scarlett Blue (MSB) staining and area of the clot was also measured on the gross photos. Student's t test was used for continuous variables and chi-squared test for categorical variables. RESULTS: A total of 1430 patients were included in this study. Mean age was 68.4±13.5 years. Overall rate of TICI 2c/3 was 67%. A total of 517 patients received tPA (36%) and 913 patients did not (64%). Mean RBC density for the tPA group was 42.97±22.62% compared to 42.80±23.18% for the non-tPA group (P=0.89). Mean WBC density for the tPA group was 3.74±2.60% compared to 3.42±2.21% for the non-tPA group (P=0.012). Mean fibrin density for the tPA group was 26.52±15.81% compared to 26.53±15.34% for the non-tPA group (P=0.98). Mean platelet density for the tPA group was 26.22±18.60% compared to 26.55±19.47% for the non-tPA group (P=0.75). tPA group also had significantly smaller clot area compared to non-tPA group. CONCLUSIONS: Our study 1430 retrieved emboli and ischemic stroke patients shows no interaction between tPA administration and clot composition. These findings suggest that tPA does not result in any histological changes in clot composition.