Intracranial Artery Calcification: Frequency, Determinants, and Modification of Outcomes from Endovascular Thrombectomy.

INTRODUCTION: Intracranial artery calcification (ICAC) is a common finding on computed tomography (CT) in patients presenting with large vessel occlusion acute ischemic stroke (LVO-AIS) and could serve as a useful biomarker of intracranial atherosclerosis and altered intracranial vessel pliability in patients undergoing endovascular thrombectomy (EVT). METHODS: This was a retrospective cohort study analyzing consecutive patients undergoing CT head prior to EVT between 2016 and 2020. Extent of ICAC proximal to the target vessel was scored using a validated grading scale examining thickness and circumferential extent of calcifications. The relationship between 3 levels of ICAC burden and procedural, clinical, and safety outcomes was analyzed. RESULTS: Among 86 patients meeting inclusion criteria, ICAC of any degree was present in 72.1%. Median ICAC score was 3 [IQR 0-4]. There was a U-shaped association between ICAC score and successful reperfusion: 90.9%, 65.7%, and 94.4% in the low, intermediate, and high ICAC score groups, respectively (p = 0.008). Use of rescue intervention, most often angioplasty and stenting, was greatest in the high ICAC score group: 3.0% vs. 5.7% vs. 22.2% (p = 0.05). Functional independence at 90 days did not differ significantly among groups (41.7% vs. 31.0% vs. 15.4%, p = 0.26), nor did rates of symptomatic intracranial hemorrhage (15.2% vs. 14.3% vs. 16.7%, p = 0.97). CONCLUSIONS: ICAC is seen on CT in nearly three-quarters of patients with LVO-AIS. Extent of ICAC has a U-shaped association with successful reperfusion, in part due to more frequent use of rescue interventions in patients with extensive ICAC.

Hemorrhagic transformation in acute ischemic stroke: hemorrhagic subtypes and symptomatic intracranial hemorrhage.

BACKGROUND: Few clinical studies perform detailed analyses of subtypes of intracranial hemorrhage (ICH) after mechanical thrombectomy (MT) used to treat acute ischemic stroke. Symptomatic intracranial hemorrhage (sICH) is a formidable complication of MT and is widely used in clinical trials as a safety outcome. However, variable definitions of sICH are used across clinical studies. OBJECTIVE: To radiographically subcategorize post-MT ICH development within this large cohort and examine overlap with sICH. Second, to examine the agreement of this definition of sICH with local site-reported occurrences of sICH to see how sICH rates change with modifications of the definitions used. METHODS: A large cohort of patients treated with MT for acute ischemic stroke (n=1395) was analyzed to (1) radiographically characterize hemorrhagic subtypes of intracranial hemorrhage (ICH) occurring after MT; (2) examine associations of hemorrhagic subtypes with sICH; and (3) compare core laboratory-adjudicated occurrences of sICH with site-reported sICH. RESULTS: The overall rate of ICH was 552/1395 patients (39.6%), and the overall rate of sICH was 47/1395 (3.4%). The most common type of ICH was hemorrhagic infarction type 1 (HI1), which represented 45.3% of all ICH cases- followed by HI2 (31.5%) and subarachnoid hemorrhage (SAH, 29.2%). Parenchymal hematoma 2 (PH2) represented only 3.3% of all ICH cases. Of the PH2 hemorrhages, only 33.3% were determined to be symptomatic. Of sICH cases, the most common ICH subtypes were HI2 (48.9%) and SAH (38.3%). Comparison of sICH rates as determined by core laboratory adjudication versus local site-reported results showed that only 14 patients were identified as having sICH with both definitions, with 47 patients total with sICH according to one definition, but not the other. CONCLUSIONS: Results of this analysis demonstrate the radiographic subtypes of ICH and also highlight the limitations of variable criteria used to define sICH, suggesting that it might be appropriate to revisit how sICH is defined post-MT. TRIAL REGISTRATION NUMBER: Clinical trial NCT03845491.

Collaterals at angiography guide clinical outcomes after endovascular stroke therapy in HERMES.

BACKGROUND: Robust collateral circulation has been linked with better reperfusion and clinical outcomes. It remains unclear how individual assessments of collateral circulation may be translated into clinical practice. METHODS: The pooled Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) angiography dataset was analyzed by a centralized, independent imaging core blinded to other clinical data. Conventional angiography was acquired immediately prior to endovascular therapy. Collaterals were graded with the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN) system and associated with baseline patient characteristics, reperfusion, and day 90 modified Rankin Score (mRS). Both 90-day all-cause mortality and day 90 mRS were modeled via multivariable logistic regression. RESULTS: Angiography was available in 376/605 (62%) patients. Baseline ASPECTS (Alberta Stroke Program Early CT Score) (p=0.043), history of diabetes mellitus (p=0.048), site of occlusion (p<0.001), and degree of subsequent Thrombolysis in Cerebral Infarction (TICI) reperfusion (p<0.001) were associated with collateral grades. ASITN collateral grade was strongly associated with ordinal mRS from baseline to 90 days in an unadjusted analysis (p<0.001). Multivariable regression demonstrated that collateral status is a strong determinant of mRS outcome in the presence of other predictors (OR=1.37 per grade, 95% CI [1.05 to 1.74], p=0.018). By comparing ORs, 1 unit of ASITN was determined to be approximately equivalent to 4.5 points of NIHSS, 11 years of age, 1.5 points of ASPECTS, or 100 min less delay from onset to puncture, in terms of impact on mRS. CONCLUSIONS: Individual collateral physiology may contribute significantly to reperfusion success and clinical outcomes after acute ischemic stroke. Building a consensus for the role of angiographic collateral assessment in the allocation of adjuvant reperfusion therapies may help galvanize a precision medicine approach in stroke.

AC-ASPECTS, ACh-ASPECTS, and H-ASPECTS: new imaging scales to assess territorial and total cerebral hemispheric ischemic injury.

Background: The extent of ischemic injury in acute stroke is assessed in clinical practice using the Acute Stroke Prognosis Early CT Score (ASPECTS) rating system. However, current ASPECTS semi-quantitative topographic scales assess only the middle cerebral artery (MCA) (original ASPECTS) and posterior cerebral (PC-ASPECTS) territories. For treatment decision-making in patients with anterior cerebral artery (ACA) occlusions and internal carotid artery (ICA) occlusions with large ischemic cores, measures of all hemispheric regions are desirable. Methods: In this cohort study, anatomic rating systems were developed for the anterior cerebral (AC-ASPECTS, 3 points) and anterior choroidal artery (ACh-ASPECTS, 1 point) territories. In addition, a total supratentorial hemisphere (H-ASPECTS, 16 points) score was calculated as the sum of the MCA ASPECTS (10 regions), supratentorial PC-ASPECTS (2 regions), AC-ASPECTS (3 regions), and ACh-ASPECTS (1 region). Three raters applied these scales to initial and 24 h CT and MR images in consecutive patients with ischemic stroke (IS) due to ICA, M1-MCA, and ACA occlusions. Results: Imaging ratings were obtained for 96 scans in 50 consecutive patients with age 74.8 (±14.0), 60% female, NIHSS 15.5 (9.25-20), and occlusion locations ICA 34%; M1-MCA 58%; and ACA 8%. Treatments included endovascular thrombectomy +/- thrombolysis in 72%, thrombolysis alone in 8%, and hemicraniectomy in 4%. Among experienced clinicians, inter-rater reliability for AC-, ACh-, and H-ASPECTS scores was substantial (kappa values 0.61-0.80). AC-ASPECTS abnormality was present in 14% of patients, and ACh-ASPECTS abnormality in 2%. Among patients with ACA and ICA occlusions, H-ASPECTS scores compared with original ASPECTS scores were more strongly associated with disability level at discharge, ambulatory status at discharge, discharge destination, and combined inpatient mortality and hospice discharge. Conclusion: AC-ASPECTS, ACh-ASPECTS, and H-ASPECTS expand the scope of acute IS imaging scores and increase correlation with functional outcomes. This additional information may enhance prognostication and decision-making, including endovascular thrombectomy and hemicraniectomy.

Symptomatic intracerebral hemorrhage in proximal and distal medium middle cerebral artery occlusion patients treated with mechanical thrombectomy.

BACKGROUND: Acute ischemic stroke (AIS) caused by distal medium vessel occlusions (DMVOs) represents a significant proportion of overall stroke cases. While intravenous thrombolysis (IVT) has been a primary treatment, advancements in endovascular procedures have led to increased use of mechanical thrombectomy (MT) in DMVO stroke patients. However, symptomatic intracerebral hemorrhage (sICH) remains a critical complication of AIS, particularly after undergoing intervention. This study aims to identify factors associated with sICH in DMVO stroke patients undergoing MT. METHODS: This retrospective analysis utilized data from the Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. Middle cerebral artery (MCA) DMVO stroke patients were included. The primary outcome measured was sICH, as defined per the Heidelberg Bleeding Classification. Univariable and multivariable logistic regression were used to identify factors independently associated with sICH. RESULTS: Among 1708 DMVO stroke patients, 148 (8.7%) developed sICH. Factors associated with sICH in DMVO patients treated with MT included older age (adjusted odds ratio (aOR) 1.01, 95% confidence interval (95% CI) 1.00 to 1.03, P=0.048), distal occlusion site (M3, M4) compared with medium occlusions (M2) (aOR 1.71, 95% CI 1.07 to 2.74, P=0.026), prior use of antiplatelet drugs (aOR 2.06, 95% CI 1.41 to 2.99, P<0.001), lower Alberta Stroke Program Early CT Scores (ASPECTS) (aOR 0.75, 95% CI 0.66 to 0.84, P<0.001), higher preoperative blood glucose level (aOR 1.00, 95% CI 1.00 to 1.01, P=0.012), number of passes (aOR 1.27, 95% CI 1.15 to 1.39, P<0.001), and successful recanalization (Thrombolysis In Cerebral Infarction (TICI) 2b-3) (aOR 0.43, 95% CI 0.28 to 0.66, P<0.001). CONCLUSION: This study provides novel insight into factors associated with sICH in patients undergoing MT for DMVO, emphasizing the importance of age, distal occlusion site, prior use of antiplatelet drugs, lower ASPECTS, higher preoperative blood glucose level, and procedural factors such as the number of passes and successful recanalization. Pending confirmation, consideration of these factors may improve personalized treatment strategies.

The National Institutes of Health Stroke Scale is comparable to the ICH score in predicting outcomes in spontaneous acute intracerebral hemorrhage.

Background: Validating the National Institutes of Health NIH Stroke Scale (NIHSS) as a tool to assess deficit severity and prognosis in patients with acute intracerebral hemorrhage would harmonize the assessment of intracerebral hemorrhage (ICH) and acute ischemic stroke (AIS) patients, enable clinical use of a readily implementable and non-imaging dependent prognostic tool, and improve monitoring of ICH care quality in administrative datasets. Methods: Among randomized trial ICH patients, the relation between NIHSS scores early after Emergency Department arrival and 3-month outcomes of dependency or death (modified Rankin Scale, mRS 3-6) and case fatality was examined. NIHSS predictive performance was compared to a current standard prognostic scale, the intracerebral hemorrhage score (ICH score). Results: Among the 384 patients, the mean age was 65 (±13), with 66% being male. The median NIHSS score was 16 (interquartile range (IQR) 9-25), the mean initial hematoma volume was 29 mL (±38), and the ICH score median was 1 (IQR 0-2). At 3 months, the mRS had a median of 4 (IQR 2-6), with dependency or death occurring in 70% and case fatality in 26%. The NIHSS and ICH scores were strongly correlated (r = 0.73), and each was strongly correlated with the 90-day mRS (NIHSS, r = 0.61; ICH score, r = 0.62). The NIHSS performed comparably to the ICH score in predicting both dependency or death (c = 0.80 vs. 0.80, p = 0.83) and case fatality (c = 0.78 vs. 0.80, p = 0.29). At threshold values, the NIHSS predicted dependency or death with 74.1% accuracy (NIHSS 17.5) and case fatality with 75.0% accuracy (NIHSS 18.5). Conclusion: The NIHSS forecasts 3-month functional and case fatality outcomes with accuracy comparable to the ICH Score. Widely documented in routine clinical care and administrative data, the NIHSS can serve as a valuable measure for clinical prognostication, therapy development, and case-mix risk adjustment in ICH patients.Clinical trial registrationClinicaltrials.gov, NCT00059332.

Endovascular therapy versus best medical management in distal medium middle cerebral artery acute ischaemic stroke: a multinational multicentre propensity score-matched study.

BACKGROUND: The efficacy of endovascular treatment (EVT) in acute ischaemic stroke due to distal medium vessel occlusion (DMVO) remains uncertain. Our study aimed to evaluate the safety and efficacy of EVT compared with the best medical management (BMM) in DMVO. METHODS: In this prospectively collected, retrospectively reviewed, multicentre cohort study, we analysed data from the Multicentre Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy registry. Patients with acute ischaemic stroke due to DMVO in the M2, M3 and M4 segments who underwent EVT or received BMM were included. Primary outcome measures comprised 10 co-primary endpoints, including functional independence (mRS 0-2), excellent outcome (mRS 0-1), mortality (mRS 6) and haemorrhagic complications. Propensity score matching was employed to balance the cohorts. RESULTS: Among 2125 patients included in the primary analysis, 1713 received EVT and 412 received BMM. After propensity score matching, each group comprised 391 patients. At 90 days, no significant difference was observed in achieving mRS 0-2 between EVT and BMM (adjusted OR 1.00, 95% CI 0.67 to 1.50, p>0.99). However, EVT was associated with higher rates of symptomatic intracerebral haemorrhage (8.4% vs 3.0%, adjusted OR 3.56, 95% CI 1.69 to 7.48, p<0.001) and any intracranial haemorrhage (37% vs 19%, adjusted OR 2.61, 95% CI 1.81 to 3.78, p<0.001). Mortality rates were similar between groups (13% in both, adjusted OR 1.48, 95% CI 0.87 to 2.51, p=0.15). CONCLUSION: Our findings suggest that while EVT does not significantly improve functional outcomes compared with BMM in DMVO, it is associated with higher risks of haemorrhagic complications. These results support a cautious approach to the use of EVT in DMVO and highlight the need for further prospective randomised trials to refine treatment strategies.

Pretreatment Predictors of Very Poor Clinical Outcomes in Medium Vessel Occlusion Stroke Patients Treated with Mechanical Thrombectomy.

BACKGROUND: Acute ischemic stroke (AIS) from primary medium vessel occlusions (MeVO) is a prevalent condition associated with substantial morbidity and mortality. Despite the common use of mechanical thrombectomy (MT) in AIS, predictors of poor outcomes in MeVO remain poorly characterized. METHODS: In this prospectively collected, retrospectively reviewed, multicenter, multinational study, data from the MAD-MT registry were analyzed. The study included 1,568 patients from 37 academic centers across North America, Asia, and Europe, treated with mechanical thrombectomy (MT), with or without intravenous tissue plasminogen activator (IVtPA), between September 2017 and July 2021. RESULTS: Among the 1,568 patients, 347 (22.2%) experienced very poor outcomes (mRS 5-6). Key predictors of poor outcomes were advanced age (OR: 1.03; 95% CI: 1.02 to 1.04; p < 0.001), higher baseline NIHSS scores (OR: 1.07; 95% CI: 1.05 to 1.10; p < 0.001), pre-operative glucose levels (OR: 1.01; 95% CI: 1.00 to 1.02; p < 0.001), and a baseline mRS of 4 (OR: 2.69; 95% CI: 1.25 to 5.82; p = 0.011). The multivariable model demonstrated good predictive accuracy with an area under the receiver operating characteristic (ROC) curve of 0.76. CONCLUSIONS: This study demonstrates that advanced age, higher NIHSS scores, elevated pre-stroke mRS, and pre-operative glucose levels significantly predict very poor outcomes in AIS-MeVO patients who received MT. These findings highlight the importance of a comprehensive risk assessment in primary MeVO patients for personalized treatment strategies. However, they also suggest a need for cautious patient selection for endovascular thrombectomy. Further prospective studies are needed to confirm these findings and explore targeted therapeutic interventions.

Performance Metrics, Algorithms, and Applications of Artificial Intelligence in Vascular and Interventional Neurology: A Review of Basic Elements.

Artificial intelligence (AI) is currently being used as a routine tool for day-to-day activity. Medicine is not an exception to the growing usage of AI in various scientific fields. Vascular and interventional neurology deal with diseases that require early diagnosis and appropriate intervention, which are crucial to saving patients' lives. In these settings, AI can be an extra pair of hands for physicians or in conditions where there is a shortage of clinical experts. In this article, the authors have reviewed the common metrics used in interpreting the performance of models and common algorithms used in this field.

Mode of Onset Modifies the Effect of Time to Endovascular Reperfusion on Clinical Outcomes after Acute Ischemic Stroke: An Analysis of the DAWN Trial.

OBJECTIVE: We aimed to assess the impact of time to endovascular thrombectomy (EVT) on clinical outcomes in the DAWN trial, while also exploring the potential effect modification of mode of stroke onset on this relationship. METHODS: The association between every 1-h treatment delay with 90-day functional independence (modified Rankin Scale [mRS] score 0-2), symptomatic intracranial hemorrhage, and 90-day mortality was explored in the overall population and in three modes of onset subgroups (wake-up vs. witnessed vs. unwitnessed). RESULTS: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6 to 12 hours and 12 to 24 hours time window, respectively. Considering all three modes of onset together, there was no statistically significant association between time last seen well to randomization with either functional independence or mortality at 90 days in either the endovascular thrombectomy (mRS 0-2 1-hour delay OR 1.07; 95% CI 0.93-1.24; mRS 6 OR 0.84; 95% CI 0.65-1.03) or medical management (mRS 0-2 1-hour delay OR 0.98; 95% CI 0.80-1.14; mRS 6 1-hour delay OR 0.94; 95% CI 0.79-1.09) groups. Moreover, there was no significant interaction between treatment effect and time (p = 0.439 and p = 0.421 for mRS 0-2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between time last seen well to successful reperfusion (modified Treatment in Cerebral Infarction ≥2b) and 90-day functional independence showed a significant interaction with mode of presentation (p = 0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p = 0.018) negative slope in wake-up patients. There was no association between treatment times and symptomatic intracranial hemorrhage. INTERPRETATION: Mode of onset modifies the effect of time to reperfusion on thrombectomy outcomes, and should be considered when exploring different treatment paradigms in the extended window. ANN NEUROL 2024;96:356-364.

Placing the balloon-guide catheter in the high cervical segment of the internal carotid artery is associated with improved recanalization.

BACKGROUND: Mechanical thrombectomy (MT) is part of the standard of care for stroke treatment, and improving its efficacy is one of the main objectives of clinical investigation. Of importance is placement of the distal end of balloon-guided catheters (BGC). We aim to determine if this influences outcomes. METHODS: We analyzed data from the ASSIST Registry, an international, multicenter prospective study of 1492 patients. We divided patients treated with BGC according to the placement of the BGC: low cervical (LCG (the lower 2/3 of cervical internal carotid artery (ICA)) or high cervical (HCG (upper 1/3 of cervical ICA, petro-lacerum or higher)). We analyzed characteristics and outcomes overall and stratified on the primary MT technique: Stent-Retriever only (SR Classic), Combined use of aspiration catheter and SR (Combined), and Direct Aspiration (ADAPT). RESULTS: Our study included 704 subjects -323 in the low cervical and 381 in the high cervical groups. Statistical differences were seen in the proportion of females and tandem lesions (both higher for LCG). Placing the BGC in the high cervical segment is associated with better recanalization rates (expanded treatment in cerebral infarction (eTICI) score of 2c-3) at the end of the procedure (P<0.0001) and shorter procedures (P=0.0005). After stratifying on the three primary techniques (SR Classic, Combined, and ADAPT), placing the BGC in the high segment is associated with a better first-pass effect (FPE), less distal emboli, and better clinical outcomes in the SR Classic technique. CONCLUSIONS: Placing the distal end of the BGC at the high cervical segment or higher is associated with better recanalization.

Developing a Coordinated Registry Network for devices used for acute ischemic stroke intervention: basilar artery occlusion quality assessment pilot.

BACKGROUND: Real-world data can be helpful in evaluating endovascular therapy (EVT) in ischemic stroke care. We conducted a pilot study to aggregate data on basilar artery occlusion (BAO) EVT from existing registries in the USA. We evaluated the availability, completeness, quality, and consistency of common data elements (CDEs) across data sources. METHODS: We harmonized patient-level data from five registry data sources and assessed the availability, completeness (defined by the presence in at least four data sources), and consistency of CDEs. We assessed data quality based on seven pre-defined critical domains for BAO EVT investigation: baseline patient and disease characteristics; time metrics; description of intervention; adjunctive devices, revascularization scores, complications; post-intervention National Institutes of Health Stroke Scale scores; discharge disposition; 30-day and 90-day mortality and modified Rankin Scale (mRS) scores. RESULTS: The aggregated dataset of five registries included 493 BAO procedures between January 2013 and January 2020. In total, 88 CDEs were screened and 35 (40%) elements were considered prevalent. Of these 35 CDEs, the majority were collected for >80% of cases when aggregated. All seven pre-defined domains for BAO device investigation could be fulfilled with harmonized data elements. Most data elements were collected with consistent or compatible definitions across registries. The main challenge was the collection of 90-day outcomes. CONCLUSIONS: This pilot shows the feasibility of aggregating and harmonizing critical CDEs across registries to create a Coordinated Registry Network (CRN). The CRN with partnerships between multiple registries and stakeholders could help improve the breadth and/or depth of real-world data to help answer relevant questions and support clinical and regulatory decisions.

Cerebral venous sinus thrombosis associated with cancer: analysis of the ACTION-CVT study.

Nearly one fifth of patients with venous thromboembolism (VTE) have cancer. When both of these conditions occur, especially in cases of cerebral vein thrombosis (CVT), patient management is often challenging. The aim of this study was to compare the characteristics and event courses in patients affected by CVT with and without cancer. Consecutive patients with CVT from the ACTION-CVT cohort study were included if cancer status was reported. Risk factors as well as the clinical and radiological characteristics of patients were compared. Univariable and multivariable analyses were performed to assess variables associated with cancer. Kaplan-Meier method and log-rank test, logistic regression analysis, and propensity score matching were used to investigate any association between cancer-related CVT and study outcomes (primary outcome at 3-months: recurrent VTE or major hemorrhage; recurrent VTE; major hemorrhage; recanalization status; all-cause-death). Overall, 1,023 patients with CVT were included, of which 6.5% had cancer. Older age (adjusted odds ratio [aOR] 1.28 per decade increase; 95% confidence interval [CI] 1.08-1.52) and absence of headache (aOR 0.47; 95% CI 0.27-0.84) were independently associated with cancer. Patients with cancer had a higher risk of recurrent VTE or major hemorrhage (aOR 3.87; 95% CI 2.09-7.16), all-cause-death (aOR 7.56 95% CI 3.24-17.64), and major hemorrhage (aOR 3.70 95% CI 1.76-7.80). Recanalization rates, partial or complete, was not significantly different. CVT patients with cancer were more likely to be older, have no referred headache, and have worse outcomes compared to CVT patients without cancer.

Association of Incident Stroke Risk With an IL-18-Centered Inflammatory Network Biomarker Composite.

BACKGROUND: A coordinated network of circulating inflammatory molecules centered on the pleotropic pro-atherogenic cytokine interleukin-18 (IL-18) is linked to cerebral small vessel disease. We sought to validate the association of this inflammatory biomarker network with incident stroke risk, cognitive impairment, and imaging metrics in a sample of the Framingham Offspring Cohort. METHODS: Using available baseline measurements of serum levels of IL-18, GDF (growth and differentiation factor)-15, soluble form of receptor for advanced glycation end products, myeloperoxidase, and MCP-1 (monocyte chemoattractant protein-1) from Exam 7 of the Framingham Offspring Cohort (1998-2001), we constructed a population-normalized, equally weighted log-transformed mean Z-score value representing the average level of each serum analyte to create an inflammatory composite score (ICS5). Multivariable regression models were used to determine the association of ICS5 with incident stroke, brain magnetic resonance imaging features, and cognitive testing performance. RESULTS: We found a significant association between ICS5 score and increased risk for incident all-cause stroke (hazard ratio, 1.48 [95% CI, 1.05-2.08]; P=0.024) and ischemic stroke (hazard ratio, 1.51 [95% CI, 1.03-2.21]; P=0.033) in the Exam 7 cohort of 2201 subjects (mean age 62±9 years; 54% female) aged 45+ years with an all-cause incident stroke rate of 6.1% (135/2201) and ischemic stroke rate of 4.9% (108/2201). ICS5 and its component serum markers are all associated with the Framingham Stroke Risk Profile score (ß±SE, 0.19±0.02; P<0.0001). In addition, we found a significant inverse association of ICS5 with a global cognitive score, derived from a principal components analysis of the neuropsychological battery used in the Framingham cohort (-0.08±0.03; P=0.019). No association of ICS5 with magnetic resonance imaging metrics of cerebral small vessel disease was observed. CONCLUSIONS: Circulating serum levels of inflammatory biomarkers centered on IL-18 are associated with an increased risk of stroke and cognitive impairment in the Framingham Offspring Cohort. Linking specific inflammatory pathways to cerebral small vessel disease may enhance individualized quantitative risk assessment for future stroke and vascular cognitive impairment.

Global intracranial arterial tortuosity is associated with intracranial atherosclerotic burden.

The effect of arterial tortuosity on intracranial atherosclerosis (ICAS) is not well understood. This study aimed to evaluate the effect of global intracranial arterial tortuosity on intracranial atherosclerotic burden in patients with ischemic stroke. We included patients with acute ischemic stroke who underwent magnetic resonance angiography (MRA) and classified them into three groups according to the ICAS burden. Global tortuosity index (GTI) was defined as the standardized mean curvature of the entire intracranial arteries, measured by in-house vessel analysis software. Of the 516 patients included, 274 patients had no ICAS, 140 patients had a low ICAS burden, and 102 patients had a high ICAS burden. GTI increased with higher ICAS burden. After adjustment for age, sex, vascular risk factors, and standardized mean arterial area, GTI was independently associated with ICAS burden (adjusted odds ratio [adjusted OR] 1.33; 95% confidence interval [CI] 1.09-1.62). The degree of association increased when the arterial tortuosity was analyzed limited to the basal arteries (adjusted OR 1.48; 95% CI 1.22-1.81). We demonstrated that GTI is associated with ICAS burden in patients with ischemic stroke, suggesting a role for global arterial tortuosity in ICAS.

Comprehensive imaging analysis of intracranial atherosclerosis.

Intracranial atherosclerotic disease (ICAD) involves the build-up of atherosclerotic plaques in cerebral arteries, significantly contributing to stroke worldwide. Diagnosing ICAD entails various techniques that measure arterial stenosis severity. Digital subtraction angiography, CT angiography, and magnetic resonance angiography are established methods for assessing stenosis. High-resolution MRI offers additional insights into plaque morphology including plaque burden, hemorrhage, remodeling, and contrast enhancement. These metrics and plaque traits help identify symptomatic plaques. Techniques like transcranial Doppler, CT perfusion, computational fluid dynamics, and quantitative MRA analyze blood flow restrictions due to ICAD. Intravascular ultrasound or optical coherence tomography have a very high spatial resolution and can assess the structure of the arterial wall and the plaque from the lumen of the target vascular territory. Positron emission tomography could further detect inflammation markers. This review aims to provide a comprehensive overview of the spectrum of current modalities for atherosclerotic plaque analysis and risk stratification.

Rescue Therapy for Failed Mechanical Thrombectomy in Acute Ischemic Stroke: A Pooled Analysis of the Society of Vascular and Interventional Neurology Registry.

OBJECTIVE: We aimed to evaluate the association between rescue therapy (RT) and functional outcomes compared to medical management (MM) in patients presenting after failed mechanical thrombectomy (MT). METHODS: This cross-sectional study utilized prospectively collected and maintained data from the Society of Vascular and Interventional Neurology Registry, spanning from 2011 to 2021. The cohort comprised patients with large vessel occlusions (LVOs) with failed MT. The primary outcome was the shift in the degree of disability, as gauged by the modified Rankin Scale (mRS) at 90 days. Additional outcomes included functional independence (90-day mRS score of 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. RESULTS: Of a total of 7,018 patients, 958 presented failed MT and were included in the analysis. The RT group comprised 407 (42.4%) patients, and the MM group consisted of 551 (57.5%) patients. After adjusting for confounders, the RT group showed a favorable shift in the overall 90-day mRS distribution (adjusted common odds ratio = 1.79, 95% confidence interval [CI] = 1.32-2.45, p < 0.001) and higher rates of functional independence (RT: 28.8% vs MM: 15.7%, adjusted odds ratio [aOR] = 1.93, 95% CI = 1.21-3.07, p = 0.005) compared to the MM group. RT also showed lower rates of sICH (RT: 3.8% vs MM: 9.1%, aOR = 0.52, 95% CI = 0.28-0.97, p = 0.039) and 90-day mortality (RT: 33.4% vs MM: 45.5%, aOR = 0.61, 95% CI = 0.42-0.89, p = 0.009). INTERPRETATION: Our findings advocate for the utilization of RT as a potential treatment strategy for cases of LVO resistant to first-line MT techniques. Prospective studies are warranted to validate these observations and optimize the endovascular approach for failed MT patients. ANN NEUROL 2024;96:343-355.

Recent Translational Research Models of Intracranial Atherosclerotic Disease.

Intracranial atherosclerotic disease (ICAD) is a leading cause of ischemic stroke worldwide. However, research on the pathophysiology of ICAD is scarce due to the relative inaccessibility of histology samples and the lack of comprehensive experimental models. As a result, much of the current understanding of ICAD relies on research on extracranial atherosclerosis. This approach is problematic as intracranial and extracranial arteries are anatomically, structurally, physiologically, and metabolically distinct, indicating that intracranial and extracranial atherosclerosis likely develop through different biologic pathways. The current standard of care for ICAD treatment relies predominantly on therapeutics developed to treat extracranial atherosclerosis and is insufficient given the alarmingly high risk of stroke. To provide a definitive treatment for the disease, a deeper understanding of the pathophysiology underlying ICAD is specifically required. True mechanistic understanding of disease pathogenesis is only possible using robust experimental models. In this review, we aim to identify the advantages and limitations of the existing in vivo and in vitro models of ICAD and basic atherosclerotic processes, which may be used to inform better models of ICAD in the future and drive new therapeutic strategies to reduce stroke risk.

The impact of collateral therapeutics on stroke hemodynamics in normotensive and hypertensive rats: a step toward translation.

Introduction: Stroke interventions that increase collateral flow have the potential to salvage penumbral tissue and increase the number of patients eligible for reperfusion therapy. We compared the efficacy of two different collateral therapeutics during transient middle cerebral artery occlusion (tMCAO) in normotensive and hypertensive rats. Methods: The change in collateral and core perfusion was measured using dual laser Doppler in response to either a pressor agent (phenylephrine, 10 mg/kg iv or vehicle) or a collateral vasodilator (TM5441, 5 mg/kg iv or vehicle) given 30 min into tMCAO in male Wistar and spontaneously hypertensive rats (SHRs). Results: Pressor therapy increased collateral flow in the Wistar rats but was ineffective in the SHRs. The increase in collateral flow in the Wistar rats was associated with impaired cerebral blood flow autoregulation (CBFAR) that was intact in the SHRs. TM5441 caused a decrease in collateral perfusion in the Wistar rats and a modest increase in the SHRs. The pressor therapy reduced early infarction in both groups but increased edema in the SHRs, whereas TM5441 did not have any beneficial effects in either group. Conclusions: Thus, the pressor therapy was superior to a collateral vasodilator in increasing collateral flow and improving outcomes in the Wistar rats, likely due to pial collaterals that were pressure passive; the lack of CBF response in the SHRs to pressor therapy was likely due to intact CBFAR that limited perfusion. While TM5441 modestly increased CBF in the SHRs but not in the Wistar rats, it did not have a beneficial effect on stroke outcomes. These results suggest that collateral therapies may need to be selected for certain comorbidities.