The glymphatic system and cerebral small vessel disease.

OBJECTIVES: Cerebral small vessel disease is a group of pathologies in which alterations of the brain's blood vessels contribute to stroke and neurocognitive changes. Recently, a neurotoxic waste clearance system composed of perivascular spaces abutting the brain's blood vessels, termed the glymphatic system, has been identified as a key player in brain homeostasis. Given that small vessel disease and the glymphatic system share anatomical structures, this review aims to reexamine small vessel disease in the context of the glymphatic system and highlight novel aspects of small vessel disease physiology. MATERIALS AND METHODS: This review was conducted with an emphasis on studies that examined aspects of small vessel disease and on works characterizing the glymphatic system. We searched PubMed for relevant articles using the following keywords: glymphatics, cerebral small vessel disease, arterial pulsatility, hypertension, blood-brain barrier, endothelial dysfunction, stroke, diabetes. RESULTS: Cerebral small vessel disease and glymphatic dysfunction are anatomically connected and significant risk factors are shared between the two. These include hypertension, type 2 diabetes, advanced age, poor sleep, obesity, and neuroinflammation. There is clear evidence that CSVD hinders the effective functioning of glymphatic system. CONCLUSION: These shared risk factors, as well as the model of cerebral amyloid angiopathy pathogenesis, hint at the possibility that glymphatic dysfunction could independently contribute to the pathogenesis of cerebral small vessel disease. However, the current evidence supports a model of cascading dysfunction, wherein concurrent small vessel and glymphatic injury hinder glymphatic-mediated recovery and promote the progression of subclinical to clinical disease.

Real-World Outcomes for Basilar Artery Occlusion Thrombectomy With Mild Deficits: The National Inpatient Sample.

BACKGROUND: Thrombectomy for basilar artery occlusion (BAO) has proven efficacy in patients with moderate-to-severe deficits, but has unclear benefits for those with mild symptoms. METHODS: Using an observational cohort design, the US National Inpatient Sample (2018-2020) was queried for adult patients with basilar artery occlusion and National Institutes of Health Stroke Scale (NIHSS) <10 for patients treated with thrombectomy versus medical management. The primary outcome of routine discharge (to home or self-care) was evaluated using multivariable logistic regression and propensity score matching, adjusted for baseline characteristics, stroke severity, and treatment with thrombolysis. RESULTS: Of 17 019 with basilar artery occlusion, 5795 patients met the criteria for inclusion criteria for our study, and 880 (15.4%) were treated with endovascular thrombectomy. In the propensity score-matched cohort, 880 patients were treated with medical management and endovascular thrombectomy, respectively. In multivariable regression, endovascular thrombectomy was associated with both an increased odds of routine discharge (odds ratio, 1.95 [95% CI, 1.31-2.90]; P=0.001) and a decreased length of hospital stay (B, -0.74 [95% CI, -1.36 to -0.11]; P=0.02) compared with medical management. In the propensity score matched cohort, endovascular thrombectomy remained associated with greater odds of routine discharge (2.01 [95% CI, 1.21-3.34]; P=0.007) but no difference in length of hospital stay (B, -0.22 [95% CI, -0.90 to 0.46]; P=0.53). CONCLUSIONS: Routine discharge was more common in this representative US cohort of patients with basilar artery occlusion and National Institutes of Health Stroke Scale <10 who underwent thrombectomy compared to conventional medical management. These findings suggest thrombectomy may be associated with better functional outcomes despite lower National Institutes of Health Stroke Scale and should be validated in a clinical trial setting.

Underlying intracranial atherosclerotic disease is associated with worse outcomes in acute large vessel occlusion undergoing endovascular thrombectomy.

BACKGROUND: Data on large vessel occlusion (LVO) management due to intracranial atherosclerotic disease (ICAD) are scarce. OBJECTIVE: To compare clinical outcomes between patients with ICAD and those without ICAD following mechanical thrombectomy (MT). METHODS: We performed a retrospective analysis of consecutive patients who underwent MT for LVO in a large academic comprehensive stroke center, and compared in-hospital mortality, 90-day mortality, favorable functional outcome at 90 days, and symptomatic intracranial hemorrhage (ICH) using chi-squared tests and multivariate logistic regression analyses. We defined ICAD as observable plaque at occlusion site post-thrombectomy. RESULTS: Among 215 patients (mean age 67.1 ± 16.0 years; 60.5% female; 83.6% Black, median NIHSS score 16), ICAD was present in 38 patients (17.7%). Diabetes and dyslipidemia were more common in those with ICAD (57.9% vs. 38.4%, p = 0.027 and 29.0% vs. 14.7%, p = 0.035, respectively). Substantial reperfusion (TICI ≥2b) was achieved less often (84.2% vs. 94.4%, p = 0.031) but symptomatic ICH was also less common in ICAD patients (0% vs. 9.0%, p = 0.081). In-hospital and 90-day mortality were more common (36.8% vs. 15.8%, p = 0.003 and 52.6% vs. 26.6%, p = 0.002, respectively) and favorable functional outcome (mRS 0-2) at 90 days was less common (7.9% vs. 33.9%, p = 0.001) in ICAD patients. After adjusting for prognostic variables, ICAD was independently associated with in-hospital mortality (OR=4.1, 95% CI 1.7-9.7), 90-day mortality (OR=3.7, 95% CI 1.6-8.6), and poor functional outcome at 90 days (OR=5.5, 95% CI 1.6-19.4). CONCLUSION: Symptomatic ICAD in a predominantly African American cohort is associated with increased odds of mortality and poor functional outcome at 90 days in patients with LVO undergoing MT.

Predictors of very early stroke recurrence in the POINT trial population.

BACKGROUND: Recent trials of acute secondary prevention in patients with minor ischemic stroke or transient ischemic attack (TIA) have demonstrated high rates of early recurrence within days of the initial event. Identifying clinical features associated with early recurrence may guide focused management. METHODS: Using logistic regression applied to the data of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, we evaluated what baseline clinical factors predict outcome events occurring within 7 days of randomization. RESULTS: In the POINT trial, 181 subjects (3.7%) had early recurrence, defined as primary outcome events within 7 days of trial entry, whereas only 100 outcome events occurred over the remainder of the 90 day trial. Protective effects of dual antiplatelet therapy with clopidogrel plus aspirin were seen only as a reduction in these early recurrences, without any impact on later events. In univariate analysis, systolic blood pressure, diastolic blood pressure, serum glucose, initial carotid imaging results, study cohort (minor stroke or TIA), and treatment assignment were significantly associated with early recurrence. Multivariate logistic regression analysis identified a number of factors with significant independent associations with early recurrence, including carotid stenosis or occlusion (Odds Ratio [OR] 2.77; 95% confidence interval [CI] 1.78-4.31), cohort (minor stroke versus TIA) (OR 1.86; 95% CI 1.33-2.58), race (OR 1.57; 95% CI 1.10-2.25), baseline statin use (OR 0.68; 95% CI 0.49-0.95), systolic blood pressure (OR 1.10; 95% CI 1.03-1.18), serum glucose (OR 1.03; 95% CI 1.01-1.05), and age (OR 1.02; 95% CI 1.00-1.03). Receiver Operator Characteristic (ROC) analysis showed a 70% accuracy of the resulting logistic model in predicting early recurrence. CONCLUSIONS: Early recurrence is high, and is concentrated in the first 7 days, in patients with minor stroke or TIA. A number of baseline clinical factors, including carotid disease, presentation with minor stroke rather than TIA, race, absence of statin usage, systolic blood pressure, and serum glucose, are independently associated with early event recurrence in the POINT trial population.

Two-State Kinetic Model of Rates of Stroke Recurrence in the POINT Study Population.

BACKGROUND AND PURPOSE: Following an acute ischemic stroke or transient ischemic attack, 2 rates of stroke recurrence are suggested by data from trials of acute secondary prevention treatments: a transient rapid rate followed by a persisting slower rate of stroke. METHODS: A kinetic model was constructed based on underlying vulnerable and stabilized states of patients following acute ischemic events related by fixed transition rates. Its predictions were fitted by nonlinear regression to the observed timing of outcome events in patients in the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke). RESULTS: The modeled survivor function produced a close fit to the observed data. The model's predicted kinetic rates suggest that, among subjects in the control group, the event rate was 100-fold higher in the vulnerable state than in the stabilized state. Active treatment halved this rapid rate and had little effect on event rates in the stabilized state. If at least one-tenth of the study population began in the vulnerable state, the rate of transition from the vulnerable to the stabilized state was still faster, with a half-life of only 1 to 2 days. CONCLUSIONS: Examination of kinetics of stroke occurrence, and of the rates associated with modeled state transitions, may provide insights into the underlying pathophysiological events that are targets for acute secondary prevention of stroke.

Intracranial Hemorrhage in Hospitalized Patients: An Infrequently Studied Condition with High Mortality.

BACKGROUND: Intracranial hemorrhage (ICH) may occur in patients admitted to the hospital for unrelated medical conditions, resulting in prolonged hospitalization and worse prognosis. We aim to assess the clinical presentation and outcomes of in-hospital ICH compared to patients with ICH presenting from the community. METHODS: We conducted a retrospective analysis of all acute stroke alerts diagnosed with ICH in an urban academic hospital over a 4-year period. Demographics, clinical presentation, use of antithrombotic therapy, and presence of coagulopathy were recorded. ICH score and a sequential organ failure assessment score were calculated during the initial assessment. Initial head computed tomography was reviewed to determine ICH subtype, location, and volume of the hematoma. In-hospital mortality and discharge disposition were used as surrogate of clinical outcome. RESULTS: From the 1965 stroke alert cases analyzed over the studied years, 145 (7.4%) were diagnosed with ICH. Overall, the mean age was 62.9 ± 13.9 and 53.7% were women. Thirty-two patients (22%) developed ICH in the inpatient setting and 113 (78%) presented from the community. Systolic blood pressure at presentation was lower in the in-hospital group (p < 0.01). Inpatients who developed ICH were more likely than community ICH patients to be on combination of antiplatelet agents (21.9% vs. 5.3%, p < 0.05) or therapeutic heparinoids (21.9% vs. 0.9%, p < 0.01). Also, In-hospital ICH patients had a higher rate of spontaneous or iatrogenic coagulopathy (65.6% vs. 10.6%, p < 0.01) and thrombocytopenia (31.3% vs. 1.8%, p < 0.01). Lobar hemorrhages were more prevalent in the in-hospital group (82.6% vs. 39.1%, p < 0.01) and the mean hematoma volume was higher (40.9 ± 43.1 mL vs. 24.1 ± 30.4 mL; p < 0.02). Median ICH score in the in-hospital group was not statistically different from the emergency department group: 2 (IQR: 0-3) versus 1 (IQR: 0-3). When comparing patients with in-hospital ICH and those from the community, the short-term mortality was higher in the former group (81% vs. 31%, p < 0.01). The incidence of withdrawal of life-sustaining therapies as a proximate mechanism of death was higher, but not statistically significant, in the in-hospital group (86% vs. 61%). CONCLUSION: ICH is a critical complication in the inpatient setting, predominantly occurring in already ill patients with underlying spontaneous or iatrogenic coagulopathy. Large volume lobar intraparenchymal hemorrhage is a common radiographic finding. ICH is frequently a catastrophic event and powerfully weighs in with end-of-life discussion, resulting in high short-term mortality rate.

Ipsilateral Nonstenotic Carotid Disease in Minor Ischemic Stroke: an Exploratory Analysis of The POINT Randomized Clinical Trial.

BACKGROUND AND AIM: Ipsilateral nonstenotic carotid disease is increasingly recognized as an etiology of ischemic stroke, however tailored treatment strategies are lacking. We aimed to examine clinical characteristics and treatment effects in patients with minor ischemic stroke associated with ipsilateral nonstenotic carotid disease in the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. METHODS: We performed an exploratory analysis of the interaction of the treatment effects of aspirin plus clopidogrel versus aspirin monotherapy, stratified by presence of ipsilateral nonstenotic carotid disease in patients with minor ischemic stroke in the POINT trial. RESULTS: For this exploratory analysis, 167 patients presenting with ischemic stroke and ipsilateral nonstenotic carotid disease, defined as 1%-49% carotid stenosis ipsilateral to the corresponding territory of ischemic stroke, and 833 patients no carotid disease were included. Compared to patients with no carotid disease, patients with ipsilateral nonstenotic carotid disease were older (68.5 ± 11.3 years versus 61.3 ± 12.8 years; P < 0.001), and had a higher prevalence of hypertension (76.6% versus 59.2%, P < 0.001), ischemic heart disease (13.8% versus 5.4%, P < 0.001), and tobacco use (past: 34.1% versus 25.2%, P = 0.005; present: 27.5% versus 22.8%, P = 0.005). 5.4% of patients with ipsilateral nonstenotic carotid disease had recurrent ischemic stroke within 14 days. Patients receiving dual antiplatelet therapy had a numerical reduction in recurrent ischemic stroke compared to patients receiving aspirin monotherapy, however the exploratory analysis was underpowered to detect a statistically significant difference in treatment effect (HR 0.50, 95% CI 0.18-1.40, P = 0.19). CONCLUSION: Patients with minor ischemic stroke and ipsilateral nonstenotic carotid disease had a high risk of early stroke recurrence in the POINT trial. Dual antiplatelet therapy provided a non-statistically significant reduction in recurrent ischemic stroke with no difference in safety outcomes compared to aspirin monotherapy. Further study is needed to determine if early and short duration dual antiplatelet therapy is beneficial for all patients with ipsilateral nonstenotic carotid disease.

BE-FAST: A Sensitive Screening Tool to Identify In-Hospital Acute Ischemic Stroke.

BACKGROUND: Development of acute ischemic stroke in hospitalized patients represents a significant proportion of all cerebral ischemia. Several prehospital stroke scales were developed to screen for acute ischemic stroke in the community. Despite the advent of inpatient stroke alert systems, there is a lack of validated screening tools for the inpatient population. This study aims to assess the validity of BE-FAST (Balance, Eyes, Face, Arm, Speech, Time) as a screening tool for acute ischemic stroke among inpatients. METHODS: We retrospectively analyzed all stroke alert activations at a single academic medical center between 2012 and 2016. We classified the triggering symptom as: focal neurologic deficit, aphasia, dysarthria, ataxia/vertigo/dizziness, alteration of consciousness, acute confusion, or headache. BE-FAST was applied retrospectively, and patients were classified as BE-FAST positive or negative. The final diagnosis was classified as acute ischemic stroke, transient ischemic attack , intracranial hemorrhage or noncerebrovascular diagnosis. RESULTS: Of 1965 stroke alerts, 489 were among inpatients. The mean age was 63 ± 16.1 years; 57% of patients were women (n = 1121). Acute ischemic stroke was diagnosed in 29% of all the activations (n = 567), transient ischemic attack in 12% (n = 232), intracranial hemorrhage in 8 % (n = 160) and noncerebrovascular in 51% (n = 1006). When comparing inpatient with community-onset stroke alerts, the sensitivity of BE-FAST for diagnosing acute ischemic stroke was 85% versus 94% (P = .005), with a specificity of 43% versus 23% (P < .001), respectively. However, when evaluating in-patients with an intact level of consciousness separately, BE-FAST sensitivity for diagnosing acute ischemic stroke was 92% compared to 94% in the community (P = .579). Among in-patients with acute ischemic stroke who were (1) candidates for reperfusion therapy and (2) diagnosed with acute large vessel occlusion, the sensitivity of BE-FAST was 83% and 94%, respectively. CONCLUSIONS: This is the first study to analyze the performance of BE-FAST among hospitalized patients evaluated through the inpatient stroke alert system. We found BE-FAST to be a very sensitive tool for screening for all in-hospital acute ischemic strokes, including inpatients that were candidates for acute reperfusion therapy.

Mechanical Thrombectomy for Patients with In-Hospital Ischemic Stroke: A Case-Control Study.

BACKGROUND AND AIM: Patients with in-hospital acute ischemic stroke (AIS) have, in general, worse outcomes compared to those presenting from the community, partly attributed to the numerous contraindications to intravenous thrombolysis. We aimed to identify and analyze a group of patients with in-hospital AIS who remain suitable candidates for acute endovascular therapies. METHODS: A retrospective 6-year data analysis was conducted in patients evaluated through the in-hospital stroke alert protocol in a single tertiary care university hospital to identify those with in-hospital AIS due to acute intracranial large vessel occlusion (ILVO). Feasibility and safety of mechanical thrombectomy for in-hospital AIS was assessed in a case-control study comparing inpatients to those presenting from the community. RESULTS: From 1460 in-hospital stroke alert activations, 11% had a final diagnosis of AIS (n = 167). One hundred and two patients with in-hospital AIS had emergent intracranial vessel imaging and were included in our cohort. Acute ILVO was identified in 27 patients within this cohort. Patients were younger in the ILVO group and had more severe neurologic deficit on presentation. Compared to a matched (1:2) control group of patients presenting from the community, inpatients who underwent mechanical thrombectomy achieved equivalent technical success, safety, and clinical outcomes. CONCLUSIONS: The incidence of acute ILVO in patients with in-hospital AIS who underwent emergent vessel imaging is similar to the reported incidence of ILVO in patients presenting with community-onset AIS. Among patients with in-hospital AIS secondary to ILVO, mechanical thrombectomy is a feasible and safe therapy associated with favorable outcomes.

Clinical Characteristics and Emergent Therapeutic Interventions in Patients Evaluated through the In-hospital Stroke Alert Protocol.

BACKGROUND AND PURPOSE: Emergent evaluation of inpatients with suspected acute ischemic stroke faces difficulty of symptoms recognition, false alarms, and high rate of contraindications to reperfusion therapies. We aim to assess the clinical characteristics and therapeutic interventions implemented in patients evaluated though the in-hospital Stroke Alert Protocol. METHODS: We analyzed 4 years-worth of Stroke Alert cases at a university hospital. Demographics, clinical presentation, final diagnosis, and acute interventions were compared between inpatients and those presenting to the emergency department. FINDINGS: A total of 1965 Stroke Alert cases were included: 959 (48.8%) were acute cerebrovascular events and 1006 (51.2%) were noncerebrovascular. Hospitalized patients accounted for 489 (24.9%) of Stroke Alerts and patients in the emergency department for 1476 (75.1%). Inpatients were more likely to present with nonfocal neurological deficits (46.2% versus 32.4%, P < .0001) and be diagnosed with noncerebrovascular disorders (62.4% versus 47.5%, P < .0001). Acute interventions other than thrombolysis were delivered in 77.1% of in-hospital cases. Compared to the emergency department, inpatients were more commonly managed with rectification of metabolic abnormalities (21.5% versus 13.7%, P < .001), suspension or pharmacological reversal of drugs (11% versus 3.7%, P < .001), and initiation of respiratory support (13.5% versus 9.3%, P = .01). Inpatients with acute ischemic stroke received intravenous thrombolysis less frequently (4.9% versus 23.9%, P < .001), but the endovascular treatment rate was comparable (9.8% versus 10.3%) to the emergency department. CONCLUSION: Nonfocal neurological deficits and noncerebrovascular disorders are commonly encountered during in-hospital Stroke Alerts. In the inpatient setting, intravenous thrombolysis is rarely delivered while other time-sensitive therapeutic interventions are frequently implemented.

Low Yield of Extensive Workup for Embolic Sources in Lacunar Stroke Patients.

OBJECTIVE: We aimed to evaluate the yield of extensive etiologic workup in lacunar stroke patients. BACKGROUND: As lacunar strokes are infrequently caused by thromboembolism, the clinical relevance of extensive workup for thromboembolic sources is questioned. METHODS: Among consecutive stroke admissions to a single center over 3 years, the 100 cases initially classified as lacunar stroke and a sample of 100 cases classified as non-lacunar ischemic strokes were studied. Review of brain imaging resulted in reclassification of 24 cases, and exclusion of 3 cases, producing a final cohort of 86 confirmed lacunar strokes and 111 confirmed non-lacunar strokes. In each of these cases, results of echocardiographic and vascular imaging studies were evaluated. RESULTS: Echocardiography was performed in 93% of both the lacunar stroke cases and non-lacunar stroke cases. High-risk cardiac embolic sources were found less often in lacunar than in non-lacunar stroke cases (19% versus 34%). Findings potentially requiring anticoagulant therapy were found exclusively in the non-lacunar stroke patients. Vascular imaging studies (computed tomography angiography or magnetic resonance angiography) were also performed in similar proportions of lacunar and non-lacunar stroke cases (85% versus 84%). Cerebrovascular occlusions or high-grade stenoses were frequent (62%) in non-lacunar stroke patients but less frequent (25%) in lacunar stroke patients. In the non-lacunar stroke patients, identified vascular lesions were very frequently in a vessel anatomically related to the infarction, but in lacunar stroke patients, this occurred in only 6 cases. CONCLUSIONS: Echocardiography and vascular imaging studies rarely disclose findings of etiologic relevance, or of likelihood to change management, in patients with lacunar strokes.

Basilar Artery Dolichoectasia: Prevalence and Correlates With Markers of Cerebral Small Vessel Disease in Community-Dwelling Older Adults.

BACKGROUND: Basilar artery (BA) dolichoectasia has been associated with cerebral small vessel disease (SVD). However, studies have focused on stroke patients, and results cannot be extrapolated to the population at large. In this study, we aimed to assess prevalence of BA dolichoectasia and its association with SVD in community-dwelling older adults living in rural Ecuador. METHODS: Atahualpa residents aged ≥60 years underwent brain magnetic resonance imaging and magnetic resonance angiography of intracranial vessels. Following Smoker's criteria, the mean BA diameter plus 2 standard deviation defined ectasia. In addition, a location lateral to the lateral margin of the clivus of dorsum sellae or a bifurcation at the third ventricle floor or higher defined dolichosis. Associations between BA abnormalities and imaging markers of SVD were assessed by the use of regression models adjusted for demographics and cardiovascular risk factors. RESULTS: Of 346 participants, 11 (3.2%) had ectasia, 40 (11.6%) had dolichosis, and 47 (13.6%) had dolichoectasia (ectasia, dolichosis, or both). BA diameter was only associated with severity of white matter hyperintensities (P = .038). Dolichosis was associated with deep cerebral microbleeds (P = .002) but not with white matter hyperintensities. Dolichoectasia was associated with both white matter hyperintensities (P = .031) and cerebral microbleeds (P = .001). There were no associations with lacunar infarcts or enlarged perivascular spaces in any model. CONCLUSIONS: Prevalence of BA dolichoectasia in this rural setting is similar to that reported in other populations. Associations with imaging markers of SVD differ according to whether the subject has ectasia or dolichosis.

Loss of PINK1 attenuates HIF-1α induction by preventing 4E-BP1-dependent switch in protein translation under hypoxia.

Parkinson's disease (PD) has multiple proposed etiologies with implication of abnormalities in cellular homeostasis ranging from proteostasis to mitochondrial dynamics to energy metabolism. PINK1 mutations are associated with familial PD and here we discover a novel PINK1 mechanism in cellular stress response. Using hypoxia as a physiological trigger of oxidative stress and disruption in energy metabolism, we demonstrate that PINK1(-/-) mouse cells exhibited significantly reduced induction of HIF-1α protein, HIF-1α transcriptional activity, and hypoxia-responsive gene upregulation. Loss of PINK1 impairs both hypoxia-induced 4E-BP1 dephosphorylation and increase in the ratio of internal ribosomal entry site (IRES)-dependent to cap-dependent translation. These data suggest that PINK1 mediates adaptive responses by activating IRES-dependent translation, and the impairments in translation and the HIF-1α pathway may contribute to PINK1-associated PD pathogenesis that manifests under cellular stress.

The Zoom RDL radial access system for neurointervention: An early single-center experience.

BACKGROUND: The transradial approach (TRA) for neurointerventional procedures is increasingly being used given its technical feasibility and safety. However, catheter trackability and device deliverability are reported barriers to TRA adoption. METHODS: This is the first report describing the technical feasibility and performance of using the Zoom RDL Radial Access System (Imperative Care, Inc., Campbell, CA) in 29 patients who underwent neurointerventional procedures from October 2022 to January 2023 in a single-center institution. RESULTS: Mean age of the study population was 61.9±17.2 years, 79.3% were male (23/29), and 62.1% were black (18/29). The most common procedures were stroke thrombectomy (31.0%, 9/29) and aneurysm embolization (27.6%, 8/29). All the stroke thrombectomy procedures were successfully performed; first-pass effect rate (mTICI≥2 c in one pass) was achieved in 66.7% (6/9) of cases. We used TRA in 86.2% of cases (25/29), including distal radial/snuffbox access in 31.0% (9/29) of cases. The radial diameter was >2 mm for all cases. An intermediate/aspiration catheter was used in 89.7% (26/29) of cases. Access success was achieved in 89.7% of cases (26/29); two cases required conversion from TRA to transfemoral approach (6.9%) and one case required conversion to a different guide catheter (3.4%). There were no access site complications or other Zoom RDL-related complications. One intracerebral hemorrhage, and one procedure-related thrombus were observed. CONCLUSIONS: The use of Zoom RDL Radial Access System is technically feasible and effective for complex neurointerventional procedures with low complication rates.

Endovascular Thrombectomy With or Without Thrombolysis for Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: To this date, whether to administer intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT) for stroke patients still stirs some debate. We aimed to systematically update the evidence from randomized trials comparing EVT alone vs EVT with bridging IVT. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing EVT with or without IVT in patients presenting with stroke secondary to a large vessel occlusion. We conducted meta-analyses using random-effects models to compare functional independence, mortality, and symptomatic intracranial hemorrhage (sICH), between EVT and EVT with IVT. We assessed risk of bias using the Cochrane risk-of-bias tool and certainty of evidence for each outcome using the GRADE approach. Results: Of 11,111 citations, we included 6 studies with a total of 2336 participants. We found low-certainty evidence of possibly a small decrease in the proportion of patients with functional independence (risk difference [RD] -2.0%, 95% CI -5.9% to 2.0%), low-certainty evidence that there is possibly a small increase in mortality (RD 1.0%, 95% CI -2.2% to 4.7%), and moderate-certainty evidence that there is probably a decrease in sICH (RD -1.0%, 95% CI -1.6% to .7%) for patients with EVT alone compared to EVT plus IVT, respectively. Conclusion: Low-certainty evidence shows that there is possibly a small decrease in functional independence, low-certainty evidence shows that there is possibly a small increase in mortality, and moderate-certainty evidence that there is probably a decrease in sICH for patients with EVT alone compared to EVT plus IVT.

Vulnerable and Stabilized States After Cerebral Ischemic Events: Implications of Kinetic Modeling in the SOCRATES, POINT, and THALES Trials.

BACKGROUND AND OBJECTIVES: Trials of acute secondary prevention after minor stroke or transient ischemic attack (TIA), such as SOCRATES, POINT, and THALES, demonstrate a high initial rate of recurrence after ischemic events that drop quickly to a lower rate, suggesting a transient vulnerable clinical state, which may call for different treatments than the subsequent stabilized state. A kinetic model incorporating vulnerable and stabilized states provides estimates of the distinct kinetic rates reflecting the temporal features of underlying stroke mechanisms. We aimed to compare these kinetic rates between treatments and across trials, asking whether these features point to common pathophysiologic processes underlying stroke recurrence, and inform the targeting and timing of enhanced antiplatelet therapy in recurrent stroke prevention. METHODS: Kaplan-Meier recurrence-free survival curves in the SOCRATES, POINT, and THALES trials were estimated for each treatment group and fitted by nonlinear regression to the 2-state kinetic model, producing estimates of kinetic parameters, with standard errors estimated using the nonparametric bootstrap with repetitive resampling. RESULTS: For each trial, the 2-state kinetic model fit the survival curves better than did the null (single-state) kinetic model or the Weibull model (p < 0.05). Recurrence rates in the vulnerable state (k 1 ) were 100-fold higher than in the stabilized state (k 2 ). Transition rates from the vulnerable to stabilized state (k 0 ) were still more rapid. Kinetic parameters were consistent across the trials, without significant differences between the trials. Enhanced antiplatelet regimens produced significant reductions in k 1 (aspirin alone: 0.030 ± 0.004 d-1; active treatment: 0.016 ± 0.003 d-1; p < 0.01) but did not affect k 0 or k 2 , suggesting that active treatment only affected risk in the vulnerable state. Modeling based on these kinetic parameters suggests that most of the benefit of active treatment occurred within 3 days. DISCUSSION: Across multiple trials of acute secondary prevention after minor stroke or TIA, recurrence of stroke is well-described by a 2-state kinetic model postulating vulnerable and stabilized states, with similar kinetic parameters across trials. Enhanced antiplatelet regimens only affected the recurrence rates in the vulnerable state, over a brief period. This analysis suggests that 2 distinct states follow acute cerebral ischemic events, subject to differential impact of immediate or delayed therapies.

Endovascular thrombectomy with or without thrombolysis bridging in patients with acute ischaemic stroke: protocol for a systematic review, meta-analysis of randomised trials and cost-effectiveness analysis.

INTRODUCTION: Current published guidelines and meta-analyses comparing endovascular thrombectomy (EVT) alone versus EVT with bridging intravenous thrombolysis (IVT) suggest that EVT alone is non-inferior to EVT with bridging thrombolysis in achieving favourable functional outcome. Because of this controversy, we aimed to systematically update the evidence and meta-analyse data from randomised trials comparing EVT alone versus EVT with bridging thrombolysis, and performed an economic evaluation comparing both strategies. METHODS AND ANALYSIS: We will conduct a systematic review of randomised controlled trials comparing EVT with or without bridging thrombolysis in patients presenting with large vessel occlusions. We will identify eligible studies by systematically searching the following databases from inception without any language restrictions: MEDLINE (through Ovid), Embase and the Cochrane Library. The following criteria will be used to assess eligibility for inclusion: (1) adult patients ≥18 years old; (2) randomised patients to EVT alone or to EVT with IVT; and (3) measured outcomes, including functional outcomes, at least 90 days after randomisation. Pairs of reviewers will independently screen the identified articles, extract information and assess the risk of bias of eligible studies. We will use the Cochrane Risk-of-Bias tool to evaluate risk of bias. We will also use the Grading of Recommendations, Assessment, Development and Evaluation approach to assess the certainty in evidence for each outcome. We will then perform an economic evaluation based on the extracted data. ETHICS AND DISSEMINATION: This systematic review will not require a research ethics approval because no confidential patient data will be used. We will disseminate our findings by publishing the results in a peer-reviewed journal and via presentation at conferences. PROSPERO REGISTRATION NUMBER: CRD42022315608.

Intravenous cangrelor use for neuroendovascular procedures: a two-center experience and updated systematic review.

Background: The optimal antiplatelet therapy regimen for certain neuroendovascular procedures remains unclear. This study investigates the safety and feasibility of intravenous dose-adjusted cangrelor in patients undergoing acute neuroendovascular interventions. Methods: We conducted a retrospective chart review of all consecutive patients on intravenous cangrelor for neuroendovascular procedures between September 1, 2020, and March 13, 2022. We also conducted an updated systematic review and meta-analysis using PubMed, Scopus, Web of Science, Embase and the Cochrane Library up to February 22, 2023. Results: In our cohort, a total of 76 patients were included [mean age (years): 57.2 ± 18.2, males: 39 (51.3), Black: 49 (64.5)]. Cangrelor was most used for embolization and intracranial stent placement (n = 24, 32%). Approximately 44% of our patients had a favorable outcome with a modified Rankin Scale (mRS) score of 0 to 2 at 90 days (n = 25/57); within 1 year, 8% of patients had recurrent or new strokes (n = 5/59), 6% had symptomatic intracranial hemorrhage [sICH] (4/64), 3% had major extracranial bleeding events (2/64), and 3% had a gastrointestinal bleed (2/64). In our meta-analysis, 11 studies with 298 patients were included. The pooled proportion of sICH and intraprocedural thromboembolic complication events were 0.07 [95% CI 0.04 to 1.13] and 0.08 [95% CI 0.05 to 0.15], respectively. Conclusion: Our study found that intravenous cangrelor appears to be safe and effective in neuroendovascular procedures, with low rates of bleeding and ischemic events. However, further research is needed to compare different dosing and titration protocols of cangrelor and other intravenous agents.

Acute Secondary Prevention of Ischemic Stroke: Overlooked No Longer.

Recent studies of interventions initiated acutely following onset of minor ischemic stroke or transient ischemic attack (TIA) have disclosed early stroke recurrence rates that are substantially higher than long-term recurrence rates and that can be reduced by acute antiplatelet treatment interventions. These observations, bolstered by analysis based on kinetic modeling of the time course of recurrence following initial events, suggest that acute stroke patients experience an underlying vulnerable state that quickly transitions to a more stable state. Some evidence also supports the benefits of early treatment with direct-acting oral anticoagulants in cardioembolic stroke and of continuation or early initiation of statin therapy in atherosclerotic stroke. Treatment of ischemic stroke should address the transient vulnerable state that follows the initial event, employing measures aiming to avert early recurrence of thromboembolism and to promote stabilization of vulnerable arterial plaque. These measures constitute acute secondary prevention following ischemic stroke.