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.

Higher Procedural Volumes Are Associated with Faster Treatment Times, Better Functional Outcomes, and Lower Mortality in Patients Undergoing Endovascular Treatment for Acute Ischemic Stroke.

OBJECTIVE: We aimed to characterize the association of hospital procedural volumes with outcomes among acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT). METHODS: This was a retrospective, observational cohort study using data prospectively collected from January 1, 2016 to December 31, 2019 in the Get with the Guidelines-Stroke registry. Participants were derived from a cohort of 60,727 AIS patients treated with EVT within 24 hours at 626 hospitals. The primary cohort excluded patients with pretreatment National Institutes of Health Stroke Scale (NIHSS) < 6, onset-to-treatment time > 6 hours, and interhospital transfers. There were 2 secondary cohorts: (1) the EVT metrics cohort excluded patients with missing data on time from door to arterial puncture and (2) the intravenous thrombolysis (IVT) metrics cohort only included patients receiving IVT ≤4.5 hours after onset. RESULTS: The primary cohort (mean ± standard deviation age = 70.7 ± 14.8 years; 51.2% female; median [interquartile range] baseline NIHSS = 18.0 [13-22]; IVT use, 70.2%) comprised 21,209 patients across 595 hospitals. The EVT metrics cohort and IVT metrics cohort comprised 47,262 and 16,889 patients across 408 and 601 hospitals, respectively. Higher procedural volumes were significantly associated with higher odds (expressed as adjusted odds ratio [95% confidence interval] for every 10-case increase in volume) of discharge to home (1.03 [1.02-1.04]), functional independence at discharge (1.02 [1.01-1.04]), and lower rates of in-hospital mortality (0.96 [0.95-0.98]). All secondary measures were also associated with procedural volumes. INTERPRETATION: Among AIS patients primarily presenting to EVT-capable hospitals (excluding those transferred from one facility to another and those suffering in-hospital strokes), EVT at hospitals with higher procedural volumes was associated with faster treatment times, better discharge outcomes, and lower rates of in-hospital mortality. ANN NEUROL 2023.

Neurological Events Reported after COVID-19 Vaccines: An Analysis of VAERS.

OBJECTIVE: To identify the rates of neurological events following administration of mRNA (Pfizer, Moderna) or adenovirus vector (Janssen) vaccines in the U.S.. METHODS: We utilized publicly available data from the U.S. Vaccine Adverse Event Reporting System (VAERS) collected between January 1, 2021-June 14, 2021. All free text symptoms that were reported within 42 days of vaccine administration were manually reviewed and grouped into 36 individual neurological diagnostic categories. Post-vaccination neurological event rates were compared between vaccine types and to age-matched baseline incidence rates in the U.S. and rates of neurological events following COVID. RESULTS: Of 306,907,697 COVID vaccine doses administered during the study timeframe, 314,610 (0.1%) people reported any adverse event and 105,214 (0.03%) reported neurological adverse events in a median of 1 day (IQR0-3) from inoculation. Guillain-Barre Syndrome (GBS), and cerebral venous thrombosis (CVT) occurred in fewer than 1 per 1,000,000 doses. Significantly more neurological adverse events were reported following Janssen (Ad26.COV2.S) vaccination compared to either Pfizer-BioNtech (BNT162b2) or Moderna (mRNA-1273; 0.15% versus 0.03% versus 0.03% of doses, respectively,P<0.0001). The observed-to-expected ratios for GBS, CVT and seizure following Janssen vaccination were ≥1.5-fold higher than background rates. However, the rate of neurological events after acute SARS-CoV-2 infection was up to 617-fold higher than after COVID vaccination. INTERPRETATION: Reports of serious neurological events following COVID vaccination are rare. GBS, CVT and seizure may occur at higher than background rates following Janssen vaccination. Despite this, rates of neurological complications following acute SARS-CoV-2 infection are up to 617-fold higher than after COVID vaccination. This article is protected by copyright. All rights reserved.

Timing of headache after COVID-19 vaccines and its association with cerebrovascular events: An analysis of 41,700 VAERS reports.

BACKGROUND: Delayed-onset of headache seems a specific feature of cerebrovascular events after COVID-19 vaccines. METHODS: All consecutive events reported to the United States Vaccine Adverse Reporting System following COVID-19 vaccines (1 January to 24 June 2021), were assessed. The timing of headache onset post-vaccination in subjects with and without concomitant cerebrovascular events, including cerebral venous thrombosis, ischemic stroke, and intracranial haemorrhage was analysed. The diagnostic accuracy in predicting concurrent cerebrovascular events of the guideline- proposed threshold of three-days from vaccination to headache onset was evaluated. RESULTS: There were 314,610 events following 306,907,697 COVID-19 vaccine doses, including 41,700 headaches, and 178/41,700 (0.4%) cerebrovascular events. The median time between the vaccination and the headache onset was shorter in isolated headache (1 day vs. 4 (in cerebral venous thrombosis), 3 (in ischemic stroke), or 10 (in intracranial hemorrhage) days, all P < 0.001). Delayed onset of headache had an area under the curve of 0.83 (95% CI: 0.75-0.97) for cerebral venous thrombosis, 0.70 (95% CI: 0.63-76) for ischemic stroke and 0.76 (95% CI: 0.67-84) for intracranial hemorrhage, and >99% negative predictive value. CONCLUSION: Headache following COVID-19 vaccination occurs within 1 day and is rarely associated with cerebrovascular events. Delayed onset of headache 3 days post-vaccination was an accurate diagnostic biomarker for the occurrence of a concomitant cerebrovascular events.

Impact of Embolisate Penetration, Type, and Technique on Results After Standalone Middle Meningeal Artery Embolization for Chronic Subdural Hematoma.

BACKGROUND AND OBJECTIVES: Middle meningeal artery embolization (MMAE) has emerged as a promising modality for chronic/subacute subdural hematoma treatment; however, consensus regarding embolization technique and embolisate has not been achieved. We thus sought to compare the efficacy of distinct MMAE techniques and embolisate. METHODS: An institutional registry was reviewed to identify patients undergoing standalone MMAE for symptomatic chronic/subacute subdural hematoma. Surgical rescue rate and time preceding 50% hematoma resolution were evaluated across 3 technical groups: aggressive penetration (AP), nonaggressive penetration with proximal coil embolization (NP-PC), and nonaggressive penetration alone (NP). Effect sizes were adjusted for demographic, neurological and radiological features through multivariable logistic and Cox regression. RESULTS: Among 117 procedures, 33.3% achieved AP, 36.8% had NP-PC, and 29.9% had NP. The rate of surgical rescue was 2.6% after AP, 9.3% for NP-PC, and 11.4% for NP. In patients not undergoing rescue surgery, 82.4% achieved hematoma resolution ≥50% at a median imaging follow-up of 56 days; AP or NP-PC were each statistically significantly associated with enhanced hematoma resolution as compared with NP (P = .02). Similarly, sensitivity analysis within medium-size hematoma and antiplatelet/anticoagulation-at-admission subgroups revealed a superiority of resolution after AP or NP-PC. A unique, comparative secondary analysis of liquid embolisate (Onyx vs n-butyl cyanoacrylate) revealed no impact on rate of surgical rescue or hematoma resolution. CONCLUSION: AP was associated with the lowest rate of surgical rescue, while both AP and NP-PC were associated with improved rates of hematoma resolution.

Distal Medium Vessel Occlusion Strokes: Understanding the Present and Paving the Way for a Better Future.

Distal medium vessel occlusions (DMVOs) are thought to cause as many as 25% to 40% of all acute ischemic strokes and may result in substantial disability amongst survivors. Although intravenous thrombolysis (IVT) is more effective for distal than proximal vessel occlusions, the overall efficacy of IVT remains limited in DMVO with less than 50% of patients achieving reperfusion and about 1/3 to 1/4 of the patients failing to achieve functional independence. Data regarding mechanical thrombectomy (MT) among these patients remains limited. The smaller, thinner, and more tortuous vessels involved in DMVO are presumably associated with higher procedural risks whereas a lower benefit might be expected given the smaller amount of tissue territory at risk. Recent advances in technology have shown promising results in endovascular treatment of DMVOs with room for future improvement. In this review, we discuss some of the key technical and clinical considerations in DMVO treatment including the anatomical and clinical terminology, diagnostic modalities, the role of IVT and MT, existing technology, and technical challenges as well as the contemporary evidence and future treatment directions.

Anesthesia modality in endovascular treatment for distal medium vessel occlusion stroke: intention-to-treat propensity score-matched analysis.

BACKGROUND: The optimal anesthesia modality during endovascular treatment (EVT) for distal medium vessel occlusion (DMVO) stroke is uncertain. We aimed to evaluate the association of the anesthesia modality with procedural and clinical outcomes following EVT for DMVO stroke. METHODS: This is a multicenter retrospective analysis of a prospectively collected database. Patients were included if they had DMVO involving the middle cerebral artery-M3/4, anterior cerebral artery-A2/3, or posterior cerebral artery-P1/P2-3, and underwent EVT. The cohort was divided into two groups, general anesthesia (GA) and non-general anesthesia (non-GA), and compared based on the intention-to-treat principle as primary analysis. We used propensity scores to balance the two groups. The primary outcome was the shift in the degree of disability as measured by the 90-day modified Rankin Scale (mRS). Secondary outcomes included successful reperfusion, as well as excellent (mRS 0-1) and good (mRS 0-2) clinical outcomes at 90 days. Safety measures included procedural complications, symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. RESULTS: Among 366 DMVO thrombectomies, 61 matched pairs were eligible for analysis. Median age and National Institutes of Health Stroke Scale score as well as other baseline demographic and clinical characteristics were balanced between both groups. The GA group had no difference in the overall degree of disability (common OR 1.19, 95% CI 0.52 to 2.86, P=0.67) compared with the non-GA arm. Likewise, the GA group had comparable rates of successful reperfusion (OR 2.38, 95% CI 0.80 to 7.07, P=0.12), good/excellent clinical outcomes (OR 1.14, 95% CI 0.44 to 2.96, P=0.79/(OR 0.65, 95% CI 0.24 to 1.81, P=0.41), procedural complications (OR 1.00, 95% CI 0.19 to 5.16, P>0.99), sICH (OR 3.24, 95% CI 0.83 to 12.68, P=0.09), and 90-day mortality (OR 1.43, 95% CI 0.48 to 4.27, P=0.52) compared with the non-GA group. CONCLUSIONS: In patients with DMVO, our study showed that GA and non-GA groups had similar procedural and clinical outcomes, as well as safety measures. Further larger controlled studies are warranted.

Recovery in Stroke Patients Treated With Fluoxetine Versus Placebo: A Pooled Analysis of 7,165 Patients.

BACKGROUND: Stroke is a major cause of disability and death. Stroke recovery outcomes range from functional impairment to disability. This study was designed to compare the recovery results of stroke patients treated with fluoxetine to those treated with placebo. REVIEW SUMMARY: Seventeen randomized clinical trials were identified by searching PubMed, Cochrane, Scopus, and Web of Science until June 2021. Fluoxetine enhances the National Institutes of Health Stroke Scale (NIHSS) score [mean difference (MD)=-0.67, 95% confidence interval (CI) (-1.19 to -0.15)] and the Fugl-Meyer Motor Scale (FMMS) score [MD=17.36, 95% CI (12.12-22.61)] at the 3-month follow up. However, the NIHSS score showed no significant difference between the 2 groups at 2 weeks [MD=-0.32, 95% CI (-0.72 to 0.07)] or at 6 months [MD=-0.17, 95% CI (-0.47 to 0.14)]. Fluoxetine-treated and placebo-treated patients had the same overall impact on FMMS scores at 1 month ( P =0.41). Barthel index showed no significant difference between the 2 arms at 3 months ( P =0.21) or 6 months ( P =0.68). Fluoxetine-treated patients were at a higher risk of broken bone [risk ratios (RR)=2.30, 95% CI (1.59-3.32)] and hyponatremia [RR=2.12, 95% CI (1.19-3.76)], and at lower risk of new depression [RR=0.72, 95% CI (0.61-0.84)] in comparison with placebo. CONCLUSION: The efficacy of fluoxetine on the NIHSS and FMMS is likely to take time to emerge and is expected to be transient. The Barthel index score did not differ between the fluoxetine and placebo groups. The use of fluoxetine increased the incidence of hyponatremia and bone fractures while decreasing the risk of new-onset depression.

Bailout technique for entangled stent retriever and carotid stent during tandem large vessel occlusion endovascular therapy.

BACKGROUND AND IMPORTANCE: Endovascular thrombectomy for patients with tandem occlusions could be challenging. Exposure to potential technical complications and bailout rescue techniques are of utmost importance. CLINICAL PRESENTATION: A 73-year-old woman with tandem internal carotid artery and middle cerebral artery lesions underwent an unsuccessful retrograde revascularization approach in the setting of tortuous anatomy. Antegrade approach revascularization was then pursued. Following cervical internal carotid artery revascularization, a triaxial system of aspiration catheter, microcatheter and micro guidewire was navigated through the stented curved cervical ICA and intracranial stent retriever pass was performed. Upon retrieving the clot-incorporated stent retriever with the intention to retrieve the entire stent retriever into the locally placed aspiration catheter, the triaxial system collapsed into the distal common carotid artery. Large thrombus was recovered from the aspiration catheter aspirate however the proximal end of stent retriever and distal internal carotid artery stent got tangled. After unsuccessful maneuvering to disentangle stent retriever from the internal carotid artery stent, we decided to attempt safe separation of the stent retriever from its pusher wire and leave behind the patent internal carotid artery stent/stent retriever metal construct in place. Gradual pulling pressure was applied to the stent retriever wire while maintaining distal exchange-length microwire access and fully inflated extracranial balloon over the entangled portion to ensure continuous vascular access. The stent retriever wire was then safely separated from the stent retriever and fully retracted outside the body. Delayed angiographic runs continued to demonstrate full patency of the internal carotid artery lumen. No residual dissection, spasm, or thrombus was noted. CONCLUSION: This case illustrates a novel bailout endovascular salvage technique that could be considered in such cases. These techniques minimize intraoperative complication, focus on patient safety, and promote efficiency for endovascular thrombectomy in unfavorable anatomy.

Intracranial stenting versus aggressive medical therapy for symptomatic intracranial stenosis: A meta-analysis of multicenter randomized controlled trials and an expert assessment of the current data.

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is associated with high risk of recurrent strokes despite best medical management (MM). We aimed to synthesize the evidence from randomized studies comparing intracranial stenting plus MM versus MM alone. METHODS: Comprehensive search of MEDLINE database was performed until May 2023. The data were extracted and pooled as risk ratio (RR) with 95% confidence interval (95% CI). RESULTS: We included three multicenter RCTs totaling 919 patients. As compared to MM alone, intracranial stenting was associated with statistically significant higher risks of any stroke or death (RR = 2.93, 95%CI [1.80-4.78], p < 0.0001), stroke in the same territory of qualifying artery (RR = 3.56, 95%CI [1.97-6.44], p < 0.0001), any ischemic stroke (RR = 2.22, 95%CI [1.27-3.87], p = 0.005), hemorrhagic stroke (RR = 13.49, 95%CI [2.59-70.15], p = 0.0002), and death (RR = 5.43, 95%CI [1.21-24.40], p = 0.003) within 30 days of randomization. There was a persistent lack of benefit and signals of harm at the last follow up within 1-3 years: any stroke or death (RR = 1.57, 95%CI [0.92-2.67], p = 0.1), stroke in the same territory of qualifying artery (RR = 1.84, 95%CI [0.97-3.50], p = 0.06), any ischemic stroke (RR = 1.56, 95%CI [1.11-2.20], p = 0.01), death (RR = 1.61, 95%CI [0.77-3.38], p = 0.2). The cumulative rate of stroke in the same territory of qualified artery with MM alone within the 1-3-year follow up was lower than expected, with only 47 out of the 450 (10.4%) MM alone patients suffering such events. CONCLUSION: The findings from this meta-analysis do not recommend stenting as a routine care option for the broader symptomatic ICAS patient population. The rates of recurrent strokes in ICAS patients managed with aggressive MM do not seem to be as high as anticipated. Additional multicenter RCTs including safer devices, larger sample sizes, and patients at higher risk of recurrent events are warranted.

From therapeutic nihilism to armamentarium: A meta-analysis of randomized clinical trials assessing safety and efficacy of endovascular therapy for acute large ischemic strokes.

BACKGROUND: Three recent randomized clinical trials (RCTs) investigated the potential benefit of endovascular therapy (EVT) in acute ischemic stroke patients presenting with large infarcts. We aimed to confirm the safety and efficacy of EVT in patients presenting with large infarcts and provide more precise estimations of the treatment effects using study-level meta-analysis. METHODS: Comprehensive search of MEDLINE database through PubMed till February 2023 was performed including RCTs only. The data were then extracted from the selected studies and pooled as risk ratio (RR) with 95% confidence interval (95% CI). RESULTS: There were a total of 1005 patients across the three qualifying RCTs. Regarding the functional outcomes assessed by modified Rankin Scale (mRS) score, the analyzed data demonstrated statistically significant differences in favor of thrombectomy for both independent ambulatory status (mRS 0-3: RR = 1.78, 95% CI [1.28, 2.48], p = 0.0006) and functional independence (mRS 0-2: RR = 2.54, 95% CI [1.85, 3.48], p < 0.001). The analyzed data did not demonstrate any statistically significant differences between EVT and medical management alone in terms of 90-day mortality (RR = 0.95, 95% CI [0.78, 1.16], p = 0.61), symptomatic intracranial hemorrhage (RR = 1.83, 95% CI [0.95, 3.55], p = 0.07), and need for hemicraniectomy (RR = 1.22, 95% CI [0.43, 3.41], p = 0.71). CONCLUSION: This study confirms the benefit of EVT on functional outcomes of patients presenting with large ischemic infarcts without significant differences in the rates of symptomatic intracranial hemorrhage, hemicraniectomy, or 90-day mortality.

Changes in the care of acute cerebrovascular and cardiovascular conditions during the first year of the covid-19 pandemic in 746 hospitals in the USA: retrospective analysis.

Objective: To measure the impact of the covid-19 pandemic on admissions to hospital and interventions for acute ischemic stroke and acute myocardial infarction. Design: A retrospective analysis. Setting: 746 qualifying hospitals in the USA from the Premier Healthcare Database. Participants: Patients aged 18 years and older who were admitted to hospital with a primary diagnosis of acute ischemic stroke or acute myocardial infarction between 1 March 2019 and 28 February 2021. Main outcome measures: Relative changes in volumes were assessed for acute ischemic stroke and acute myocardial infarction hospital admissions as well as intravenous thrombolysis, mechanical thrombectomy, and percutaneous coronary intervention (overall and for acute myocardial infarction only) across the first year of the pandemic versus the prior year. Mortality in hospital and length of stay in hospital were also compared across the first year of the pandemic versus the corresponding period the year prior. These metrics were explored across the different pandemic waves. Results: Among 746 qualifying hospitals, admissions to hospital were significantly reduced after the covid-19 pandemic compared with before the pandemic for acute ischemic stroke (-13.59% (95% confidence interval-13.77% to -13.41%) and acute myocardial infarction (-17.20% (-17.39% to -17.01%)), as well as intravenous thrombolysis (-9.47% (-9.99% to -9.02%)), any percutaneous coronary intervention (-17.89% (-18.06% to -17.71%)), and percutaneous coronary intervention for acute myocardial infarction (-14.36% (-14.59% to -14.12%)). During the first year of the pandemic versus the previous year, the odds of mortality in hospital for acute ischemic stroke were 9.00% higher (3.51% v 3.16%; ratio of the means 1.09 (95% confidence interval (1.03 to 1.15); P=0.0013) and for acute myocardial infarction were 18.00% higher (4.81% v 4.29%; ratio of the means 1.18 (1.13 to 1.23); P<0.0001). Conclusions: We observed substantial decreases in admissions to hospital with acute ischemic stroke and acute myocardial infarction, but an increase in mortality in hospital throughout the first year of the pandemic. Public health interventions are needed to prevent these reductions in future pandemics.

Basilar artery occlusion management: An international survey of middle versus high-income countries.

BACKGROUND AND PURPOSE: Two early basilar artery occlusion (BAO) randomized controlled trials (RCTs) did not establish the superiority of endovascular thrombectomy (EVT) over medical management. Yet many providers continued to recommend EVT. The goal of the present article is to compare physicians' diagnostic and management strategies of BAO among middle-income and high-income countries (MICs and HICs, respectively). METHODS: We conducted an international survey from January to March 2022 regarding management strategies in acute BAO, to examine clinical and imaging parameters influencing clinician management of patients with BAO. We compared responses between physicians from HIC and MIC. RESULTS: Among the 1245 respondents from 73 countries, 799 (64.2%) were from HIC, with the remaining 393 (31.6%) from MIC. Most respondents perceived that EVT was superior to medical management for acute BAO, but more so in respondents from HIC (98.0% vs. 94.2%, p < 0.01). MIC respondents were more likely to believe further RCTs were warranted (91.6% vs. 74.0%, p < 0.01) and were more likely to find it acceptable to enroll any patient who met a trial's criteria in the standard medical treatment arm (58.8% vs. 38.5%, p < 0.01). CONCLUSIONS: In an area where clinical equipoise was called into question despite the lack of RCT evidence, we found that respondents from MIC were more likely to express willingness to enroll patients with BAO in an RCT than their HIC counterparts.