Large vessel occlusion stroke due to underlying intracranial atherosclerotic disease (ICAD-LVO) is prevalent in 10 to 30% of LVOs depending on patient factors such as vascular risk factors, race and ...ethnicity, and age. Patients with ICAD-LVO derive similar functional outcome benefit from endovascular thrombectomy as other mechanisms of LVO, but up to half of ICAD-LVO patients reocclude after revascularization. Therefore, early identification and treatment planning for ICAD-LVO are important given the unique considerations before, during, and after endovascular thrombectomy. In this review of ICAD-LVO, we propose a multistep approach to ICAD-LVO identification, pretreatment and endovascular thrombectomy considerations, adjunctive medications, and medical management. There have been no large-scale randomized controlled trials dedicated to studying ICAD-LVO, therefore this review focuses on observational studies.
Endovascular therapy (EVT) has revolutionized the treatment of acute ischemic stroke. In the past few years, endovascular treatment indications have expanded to include patients being treated in the ...extended window, with large ischemic core infarction, basilar artery occlusion (BAO) thrombectomy, as demonstrated by several randomized clinical trials. Intravenous thrombolysis (IVT) bridging to mechanical thrombectomy has also been studied via several randomized clinical trials, with the overall results indicating that IVT should not be skipped in patients who are candidates for both IVT and EVT. Simplification of neuroimaging protocols in the extended window to permit non-contrast CT, CTA collaterals have also expanded access to mechanical thrombectomy, particularly in regions across the world where access to advanced imaging may not be available. Ongoing study of areas to develop include rescue stenting in patients with failed thrombectomy, medium vessel occlusion thrombectomy, and carotid tandem occlusions. In this narrative review, we summarize recent trials and key data in the treatment of patients with large ischemic core infarct, simplification of neuroimaging protocols for the treatment of patients presenting in the late window, bridging thrombolysis, and BAO EVT evidence. We also summarize areas of ongoing study including medium and distal vessel occlusion.
Growing evidence suggests breast cancer susceptibility gene (BRCA) mutations may augment cerebrovascular risk factors. With this influence in mind, we aimed to identify if BRCA mutations increased ...the prevalence of cerebral small vessel disease (CSVD).
We performed a retrospective cross-sectional analysis of adults undergoing malignancy evaluation with confirmed BRCA mutations compared to BRCA wildtype individuals. A standard-of-care brain MRI was reviewed. Chi-squared or Fisher's, Wilcoxon rank-sum and the Student's t-test analyses were used when appropriate. Adjusted logistic regression models were fit to calculate odds ratio. Multicollinearity was tested by variance inflation factor calculation and for goodness-of-fit via the Hosmer-Lemeshow test.
Of 116 individuals, 44.8% (52/116) carried a BRCA mutation. Demographic and cerebrovascular risk factors did not differ. Cerebral microbleeds were more common in those with BRCA mutation: 32.7% (17/52) vs. 17.2% (11/64), p = 0.05 with an adjusted odds ratio of 2.8 (95%CI 1.08-6.89, p = 0.03). Other markers of CSVD were similar amongst the cohort.
We identified a nearly 3-fold increase in identified cerebral microbleed in those with BRCA mutations compared with BRCA wildtype individuals suggestive of an interaction between the BRCA gene and cerebral microbleed formation. Further studies are needed to confirm our findings and to understand clinical implications.
Brain infarct growth, despite successful reperfusion, decreases the likelihood of good functional outcome after ischemic stroke. In patients undergoing reperfusion, admission glucose is associated ...with poor outcome but the effect of glucose level on infarct growth is not well studied.
This is a secondary analysis of the DEFUSE 3 trial. The primary predictor was baseline glucose level and the primary outcome is the change of the ischemic core volume from the baseline to 24-hour follow-up imaging (∆core), transformed as a cube root to reduce right skew. We included DEFUSE 3 patients who were randomized to endovascular therapy, had perfusion imaging data at baseline, an MRI at 24 hours, and who achieved TICI 2b or 3. Linear regression models, both unadjusted and adjusted, were fit to the primary outcome and all models included the baseline core volume as a covariate to normalize ∆core.
We identified 62 patients who met our inclusion criteria. The mean age was 68.1±13.1 (years), 48.4% (30/62) were men, and the median (IQR) cube root of ∆core was 2.8 (2.0-3.8) mL. There was an association between baseline glucose level and normalized ∆core in unadjusted analysis (beta coefficient 0.010, p = 0.01) and after adjusting for potential confounders (beta coefficient 0.008, p = 0.03).
In acute ischemic stroke patients with large vessel occlusion undergoing successful endovascular reperfusion, baseline hyperglycemia is associated with infarction growth. Further study is needed to establish potential neuroprotective benefits of aggressive glycemic control prior to and after reperfusion.
Ischemic events related to carotid disease are far more strongly associated with plaque instability than stenosis. 3D high‐resolution diffusion‐weighted (DW) imaging can provide quantitative ...diffusion measurements on carotid atherosclerosis and may improve detection of vulnerable intraplaque hemorrhage (IPH). The 3D DW‐stack of stars (SOS) sequence was implemented with 3D SOS acquisition combined with DW preparation. After simulation of signals created from 3D DW‐SOS, phantom studies were performed. Three healthy subjects and 20 patients with carotid disease were recruited. Apparent diffusion coefficient (ADC) values were statistically analyzed on three subgroups by using a two‐group comparison Wilcoxon–Mann–Whitney U test with p values less than 0.05: symptomatic versus asymptomatic; IPH‐positive versus IPH‐negative; and IPH‐positive symptomatic versus asymptomatic plaques to determine the relationship with plaque vulnerability. ADC values calculated by 3D DW‐SOS provided values similar to those calculated from other techniques. Mean ADC of symptomatic plaque was significantly lower than asymptomatic plaque (0.68 ± 0.18 vs. 0.98 ± 0.16 x 10−3 mm2/s, p < 0.001). ADC was also significantly lower in IPH‐positive versus IPH‐negative plaque (0.68 ± 0.13 vs. 1.04 ± 0.11 x 10−3 mm2/s, p < 0.001). Additionally, ADC was significantly lower in symptomatic versus asymptomatic IPH‐positive plaque (0.57 ± 0.09 vs. 0.75 ± 0.11 x 10−3 mm2/s, p < 0.001). Our results provide strong evidence that ADC measurements from 3D DW‐SOS correlate with the symptomatic status of extracranial internal carotid artery plaque. Further, ADC improved discrimination of symptomatic plaque in IPH. These data suggest that diffusion characteristics may improve detection of destabilized plaque leading to elevated stroke risk.
This work provides strong evidence that ADC measurements from 3D DW‐SOS correlate with symptomatic status of extracranial internal carotid artery plaque. Further, ADC further improved discrimination of symptomatic plaque in IPH. These data suggest that diffusion characteristics may improve detection of destabilized plaque leading to elevated stroke risk.
Venous thromboembolism (VTE) is a life-threatening complication of stroke. We evaluated nationwide rates and risk factors for hospital readmissions with VTE after an intracerebral hemorrhage (ICH) or ...acute ischemic stroke (AIS) hospitalization.
Using the Healthcare Cost and Utilization Project (HCUP) Nationwide Readmission Database, we included patients with a principal discharge diagnosis of ICH or AIS from 2016 to 2019. Patients who had VTE diagnosis or history of VTE during the index admission were excluded. We performed Cox regression models to determine factors associated with VTE readmission, compared rates between AIS and ICH and developed post-stroke VTE risk score. We estimated VTE readmission rates per day over a 90-day time window post-discharge using linear splines.
Of the total 1,459,865 patients with stroke, readmission with VTE as the principal diagnosis within 90 days occurred in 0.26% (3,407/1,330,584) AIS and 0.65% (843/129,281) ICH patients. The rate of VTE readmission decreased within first 4-6 weeks (P<0.001). In AIS, cancer, obesity, higher National Institutes of Health Stroke Scale (NIHSS) score, longer hospital stay, home or rehabilitation disposition, and absence of atrial fibrillation were associated with VTE readmission. In ICH, longer hospital stay and rehabilitation disposition were associated with VTE readmission. The VTE rate was higher in ICH compared to AIS (adjusted hazard ratio 2.86, 95% confidence interval 1.93-4.25, P<0.001).
After stroke, VTE readmission risk is highest within the first 4-6 weeks and nearly three-fold higher after ICH vs. AIS. VTE risk is linked to decreased mobility and hypercoagulability. Studies are needed to test short-term VTE prophylaxis beyond hospitalization in high-risk patients.
Patients with acute bilateral M1 occlusion are usually comatose at presentation and have a grave prognosis. There have been few reports of emergent treatment using endovascular reperfusion therapy ...(ERT). We describe a patient treated with simultaneous first-pass contact aspiration and review the literature for cases describing the successful use of ERT in patients with bilateral anterior circulation proximal large-vessel occlusion (LVO). A functionally independent 95-year-old woman with history of atrial fibrillation (AF) presented with altered mentation, aphasia, and weakness in all extremities. Her National Institutes of Health Stroke Scale (NIHSS) score was 13. CT angiogram and perfusion demonstrated acute mirror M1 occlusions with extensive bilateral middle cerebral artery (MCA) territory penumbra, respectively. Emergent ERT was performed with simultaneous contact aspiration within the bilateral M1s under concomitant flow arrest with a balloon guide catheter. Modified Thrombolysis in Cerebral Infarction (mTICI) grades 3 and 2c were achieved on the left and right, respectively. By postoperative day 1 (POD1), the patient had improved motor function, mentation, and communication.The technical feasibility of simultaneous contact aspiration thrombectomies for acute bilateral M1 occlusions was demonstrated with successful reperfusion of both vascular territories in a single pass lasting 28 minutes. Simultaneous thrombectomies yielded rapid recanalization and reperfusion and minimized radiation exposure. Previous cases demonstrating this technique utilized stent-retriever techniques in successive fashion, with a consequent increase in the patient’s total ischemic time. The technical success of our aggressive approach suggests it may have utility in the treatment of acute multivessel occlusions (MVOs).
Background:
Cerebral air embolism is a rare cause of acute ischemic stroke that is becoming increasingly well-described in the literature. However, the mechanism and severity of this type of injury ...can vary, with ischemia typically emerging early in the course of care. To the best of our knowledge, delayed ischemia in this setting has not yet been described.
Case Description:
A stroke code was called for an unresponsive, hospitalized, 75-year-old man. A computerized tomography (CT) scan of the head revealed air within the right greater than left hemispheric cortical veins with loss of sulcation, concerning for developing ischemia, and CT angiography revealed absent opacification of the distal cortical vessels in the right anterior cerebral artery and middle cerebral artery territories. Magnetic resonance imaging (MRI) of the brain was obtained 5.75 h after the patient’s last known well-showed small areas of subtle cortical diffusion restriction. Follow-up CT head within 24 h showed near-complete resolution of the air emboli after treatment with 100% fraction of inspired oxygen on mechanical ventilation. Subsequent MRI, performed 4 days after the initial event, showed extensive cortical diffusion restriction and cerebral edema crossing vascular territories.
Conclusion:
This case highlights that cerebral air emboli can cause delayed ischemia that may not be appreciated on initial imaging. As such, affected patients may require intensive neurocritical care management, close neurologic monitoring, and repeat imaging irrespective of initial radiographic findings.
Introduction
Vessel wall magnetic resonance imaging can improve the evaluation of intracranial atherosclerotic disease. However, pathological validation is needed to improve vessel wall magnetic ...resonance imaging techniques. Human pathology samples are not practical for such analysis, so an animal model is therefore needed.
Materials and methods
Watanabe heritable hyperlipidemic rabbits and apolipoprotein E knockout rabbits were evaluated against New Zealand white wild-type rabbits. Evaluation of intracranial arteries was performed with vessel wall magnetic resonance imaging and pathological analysis, rating the presence and severity of disease in each segment. Two-tailed t-tests were performed to compare disease occurrence and severity prevalence among rabbit subtypes. Sensitivity and specificity were calculated to assess the diagnostic accuracy of vessel wall magnetic resonance imaging.
Results
Seventeen rabbits (five Watanabe heritable hyperlipidemic, four apolipoprotein E knockout and eight New Zealand white) were analysed for a total of 51 artery segments. Eleven segments (five Watanabe heritable hyperlipidemic and six apolipoprotein E knockout) demonstrated intracranial atherosclerotic disease on pathology. Disease model animals had lesions more frequently than New Zealand white animals (P<0.001). The sensitivity and specificity of vessel wall magnetic resonance imaging for the detection of intracranial atherosclerotic disease were 68.8% and 95.2%, respectively. When excluding mild cases to assess vessel wall magnetic resonance imaging accuracy for detecting moderate to severe intracranial atherosclerotic disease lesions, sensitivity improved to 100% with unchanged specificity.
Conclusion
Intracranial atherosclerotic disease can be reliably produced and detected using 3T vessel wall magnetic resonance imaging-compatible Watanabe heritable hyperlipidemic and ApoE rabbit models. Further analysis is needed to characterize better the development and progression of the disease to correlate tissue-validated animal findings with those in human vessel wall magnetic resonance imaging studies.
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