Safety and Outcomes of Valproic Acid in Subarachnoid Hemorrhage Patients: A Retrospective Study.

Background and Purpose: Animal studies have suggested that valproic acid (VPA) is neuroprotective in aneurysmal subarachnoid hemorrhage (SAH). Potential mechanisms include an effect on cortical spreading depolarizations (CSD), apoptosis, blood-brain barrier integrity, and inflammatory pathways. However, the effect of VPA on SAH outcomes in humans has not been investigated. Methods: We conducted a retrospective analysis of 123 patients with nontraumatic SAH. Eighty-seven patients had an aneurysmal source and 36 patients did not have a culprit lesion identified. We used stepwise logistic regression to determine the association between VPA and the following: delayed cerebral ischemia (DCI), radiographic vasospasm, and discharge modified Rankin Scale (mRS) score > 3. Results: All 18 patients who received VPA underwent coil embolization of their aneurysm. VPA use did not have a significant association with DCI on adjusted analysis (Odds Ratio, OR = 1.07, 95% CI: 0.20 - 5.80). The association between VPA use and vasospasm was OR = 0.64 (0.19 - 1.98) and discharge mRS > 3 was OR = 0.45 (0.10 - 1.64). Increased age (OR = 1.04, 1.01 - 1.07) and Hunt and Hess (HH) grade > 3 (OR = 14.5, 4.31 - 48.6) were associated with an increased likelihood for poor discharge outcome (mRS > 3). Younger age (OR = 0.96, 0.93 - 0.99), mFS score = 4 (OR = 4.14, 1.81 - 9.45), and HH grade > 3 (OR = 2.92, 1.11 - 7.69) were all associated with subsequent development of radiographic vasospasm. There were no complications associated with VPA administration. Conclusion: We did not observe an association between VPA and the rate of DCI. There may have been a protective association on discharge outcome and radiographic vasospasm that did not reach statistical significance. We found that VPA use was safe and is plausible to be used in a population of SAH patients who have undergone endovascular treatment of their aneurysm. Larger, prospective studies are needed to determine the effect of VPA on outcome after SAH.

Mechanical Thrombectomy Versus Intravenous Thrombolysis in Distal Medium Vessel Acute Ischemic Stroke: A Multinational Multicenter Propensity Score-Matched Study.

Background and Purpose: The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone. Methods: This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage. Results: The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0-1 and 0-2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P<0.001). Conclusion: The results of this study indicate that while MT-IVT and IVT alone show similar functional and mortality outcomes in DMVO patients, MT-IVT presents a higher risk of hemorrhagic complications, thus MT-IVT may not routinely offer additional benefits over IVT alone for all DMVO stroke patients. Further prospective randomized trials are needed to identify patient subgroups most likely to benefit from MT-IVT treatment in DMVO.

Intracerebral hemorrhage risk after adjunct intraarterial thrombolysis in thrombectomy-treated acute ischemic stroke.

BACKGROUND AND PURPOSE: Intraarterial thrombolysis as an adjunct to mechanical thrombectomy is increasingly being considered to enhance reperfusion in acute ischemic stroke patients. Intraarterial thrombolysis may increase the risk of post-thrombectomy intracerebral hemorrhage (ICH) in certain patient subgroups. METHODS: We analyzed acute ischemic stroke patients treated with mechanical thrombectomy in a multicenter registry. The occurrence of any (asymptomatic and symptomatic) post-thrombectomy ICH was ascertained using standard definition requiring serial neurological examinations and computed tomographic scans acquired within 48 hours of the thrombectomy. We determined the risk of ICH in subgroups defined by clinical characteristics and the use of intravenous (IV) thrombolysis. RESULTS: A total of 146 (7.5%) patients received intraarterial thrombolysis among 1953 acute ischemic stroke patients who underwent mechanical thrombectomy. The proportion of patients who developed any ICH was 26 (17.8%) and 510 (28.2%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p = .006). The proportion of patients who developed symptomatic ICH was 4 (2.7%) and 30 (1.7%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p = .34). Among patients who received IV thrombolysis (n = 1042), the proportion of patients who developed any ICH was 9 (16.7%) and 294 (30.7%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p = .028). The risk was not different in strata defined by age, gender, location of occlusion, preprocedure National Institutes of Health Stroke Scale score, time interval between symptom onset and thrombectomy, Alberta Stroke Program Early CT Score, systolic blood pressure, and serum glucose concentrations. CONCLUSIONS: In patients undergoing mechanical thrombectomy, the risk of any ICH and symptomatic ICH was not increased with intraarterial thrombolysis, including in those who had already received IV thrombolytics.

Venous sinus diverticulum in patients with pulsatile tinnitus: An acquired lesion.

BACKGROUND: The etiopathogenesis of venous sinus diverticulum is controversial. Conflicting evidence has been published suggesting that venous sinus diverticulum is either a congenital or acquired lesion. METHODS: This is a case report of a single individual followed for 17 years within a single healthcare system. RESULTS: An early middle-aged woman presented with unilateral pulsatile tinnitus, vertigo, and decreased hearing. Initial imaging was unrevealing. Interval imaging after 13 years revealed the development of an ipsilateral venous sinus diverticulum. The patient was treated via endovascular stenting and coiling of the lesion with complete resolution of symptoms. CONCLUSIONS: We demonstrate that a venous sinus diverticulum in a patient with pulsatile tinnitus is an acquired lesion. Further research is warranted to better elucidate the precise etiology and pathophysiology of acquired venous sinus diverticulum, potentially guiding management strategies.

Increased peripheral leukocyte aggravates brain injury and leads to poor outcome in stroke patients receiving intravenous thrombolysis: A study based on clinical evidence.

Whether the dynamic development of peripheral inflammation aggravates brain injury and leads to poor outcome in stroke patients receiving intravenous thrombolysis (IVT), remains unclear and warrants further study. In this study, total of 1034 patients with acute ischemic stroke who underwent IVT were enrolled. Serum leukocyte variation (whether increase from baseline to 24 h after IVT), National Institutes of Health Stroke Scale (NIHSS), infarct volume, early neurologic deterioration (END), the unfavorable outcome at 3-month (modified Rankin Scale [mRS] score ≥3) and mortality were recorded. Serum brain injury biomarkers, including Glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), S100ß, neuron-specific enolase (NSE), were measured to reflect the extent of brain injury. We found that patients with increased serum leukocytes had elevated brain injury biomarkers (GFAP, UCH-L1, and S100ß), larger infarct volume, higher 24 h NIHSS, higher proportion of END, unfavorable outcome and mortality. Furthermore, an increase in serum leukocytes was independently associated with infarct volume, 24 h NIHSS, END, and unfavorable outcome at 3 months, and serum UCH-L1, S100ß, and NSE levels. These results suggest that an increase in serum leukocytes indicates severe brain injury and may be used to predict the outcome of patients with ischemic stroke who undergo IVT.

Understanding why restrictive trial eligibility criteria are inappropriate.

BACKGROUND: An important difference between explanatory and pragmatic clinical trials concerns eligibility criteria. Eligibility criteria are restrictive in explanatory trials, while pragmatic trials are more inclusive or even all-inclusive. METHODS: To better understand the diverging views regarding eligibility criteria, we examine the contrast between theoretical and clinical medicine, and 3 different research contexts: laboratory research, population studies and clinical trials. In each context we review the purpose for selecting study subjects or research material, as well as the type of inductive inference or generalization that is sought by such selection. RESULTS: In each context, selection concerns different things and serves different purposes: In the laboratory, selection concerns the homogenous research material that will help isolate a causal signal. In the epidemiological context selection concerns the (random) sampling method, designed to produce a representative sample of the population. In the clinical trial setting, selection concerns patients in need of care. Restrictive eligibility criteria become inappropriate in the care setting because the aim of the trial is not to represent a population nor to isolate a causal signal, but to find out which patients benefit from treatment. CONCLUSION: The idea of selecting patients comes from methods that belong to theoretical medicine. In the care setting, most clinical trials should be pragmatic and as inclusive as possible.

Predictive value of follow-up infarct volume on functional outcomes in middle cerebral artery M2 segment vessel occlusion stroke treated with mechanical thrombectomy.

BACKGROUND: Medium vessel occlusion (MeVO) strokes, particularly affecting the M2 segment of the middle cerebral artery, represent a critical proportion of acute ischemic strokes, posing significant challenges in management and outcome prediction. The efficacy of mechanical thrombectomy (MT) in MeVO stroke may warrant reliable predictors of functional outcomes. This study aimed to investigate the prognostic value of follow-up infarct volume (FIV) for predicting 90-day functional outcomes in MeVO stroke patients undergoing MT. METHODS: This multicenter, retrospective cohort study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, covering patients with acute ischemic stroke due to M2 segment occlusion treated with MT. We examined the relationship between 90-day functional outcomes, measured by the modified Rankin Scale (mRS), and follow-up infarct volume (FIV), assessed through CT or MRI within 12-36 h post-MT. RESULTS: Among 130 participants, specific FIV thresholds were identified with high specificity and sensitivity for predicting outcomes. A FIV ⩽5 ml was highly specific for predicting favorable and excellent outcomes. The optimal cut-off for both prognostications was identified at ⩽15 ml by the Youden Index, with significant reductions in the likelihood of favorable outcomes observed above a 40 ml threshold. Receiver Operator Curve (ROC) analyses confirmed FIV as a superior predictor of functional outcomes compared to traditional recanalization scores, such as final modified thrombolysis in cerebral infarction score (mTICI). Multivariable analysis further highlighted the inverse relationship between FIV and positive functional outcomes. CONCLUSIONS: FIV within 36 h post-MT serves as a potent predictor of 90-day functional outcomes in patients with M2 segment MeVO strokes. Establishing FIV thresholds may aid in the prognostication of stroke outcomes, suggesting a role for FIV in guiding post intervention treatment decisions and informing clinical practice. Future research should focus on validating these findings across diverse patient populations and exploring the integration of FIV measurements with other clinical and imaging markers to enhance outcome prediction accuracy.

Trial selection criteria should not be used for clinical decisions and recommendations: the thrombectomy trials example.

BACKGROUND: Despite multiple calls for more inclusive studies, most clinical trial eligibility criteria remain too restrictive. Thrombectomy trials have been no exception. METHODS: We review the landmark trials that have shown the benefits of thrombectomy, their eligibility criteria, and consequences on clinical practice. We discuss the rationale behind various reasons for exclusions. We also examine the logical problem involved in using eligibility criteria as indications for treatment. RESULTS: Most thrombectomy trials have been too restrictive. This has been shown by a plethora of follow-up studies that have refuted most of the previously recommended trial eligibility restrictions. Meanwhile, the effect of clinical recommendations based on restrictive eligibility criteria is that treatment has been denied to the majority of patients who could have benefitted. Trial eligibility criteria cannot be used to make clinical decisions or recommendations unless, like any other medical diagnosis, they have been shown capable of reliably differentiating patients into those that will, and those that will not benefit from treatment. This goal can only be achieved with all-inclusive pragmatic trials. CONCLUSION: Restrictive eligibility criteria render clinical trials incapable of guiding medical decisions or recommendations.

A prospective, randomized, controlled, interventional clinical trial to evaluate the safety and efficacy of the medical monopoint reperfusion system for aspiration thrombectomy in acute ischemic stroke patients (SUMMIT MAX): Trial rationale and design.

BACKGROUND: Treatment of large vessel occlusion (LVO) using mechanical thrombectomy with or without intravenous thrombolysis has demonstrated better outcomes compared to medical treatment alone. Large-bore aspiration catheters have been recently introduced. Their effectiveness and safety have not been demonstrated in a randomized trial. The SUMMIT MAX study is designed to address this question. METHODS: SUMMIT MAX is a randomized controlled trial where the effectiveness and safety of the large-bore Monopoint Reperfusion system (Route 92 Medical, San Mateo, CA), will be compared to the currently largest available FDA-cleared aspiration thrombectomy device the AXS Vecta Aspiration system (Stryker Neurovascular, Fremont, CA). The study is a multi-center, prospective, randomized, controlled, interventional, open label clinical trial. The hypothesis is that the effectiveness measured by the recanalization rate (modified thrombolysis in cerebrovascular infarction - mTICI) and safety measured by symptomatic intracranial hemorrhage rate (sICH) of the medical monopoint reperfusion system is non-inferior to the AXS Vecta Aspiration system. RESULTS: Up to 250 subjects are enrolled with at least 50% of subjects enrolled by US sites. The primary effectiveness endpoint is successful arterial revascularization defined as an mTICI score ≥ 2b after use of the assigned device adjudicated by an independent core lab. The primary safety endpoint is defined as sICH within 24 h (-8/+24) post-procedure. Secondary endpoints include successful arterial revascularization defined as a mTICI score ≥ 2b after use of the assigned device with or without adjunctive therapy; device-related serious adverse events; all asymptomatic hemorrhages; time from groin puncture to final angiogram; and rate of first pass effect defined as mTICI 2b after first pass with the assigned device stratified by age (≤85, ≥ 86). CONCLUSION: SUMMIT MAX is a randomized controlled trial comparing the effectiveness and safety of a new large bore class of aspiration devices to the currently largest FDA-cleared aspiration device available.

Differential efficacy of remote ischaemic conditioning in anterior versus posterior circulation stroke: A prespecified secondary analysis of the RICAMIS trial.

BACKGROUND AND PURPOSE: The benefit of remote ischaemic conditioning (RIC) in acute moderate ischaemic stroke has been demonstrated by the Remote Ischaemic Conditioning for Acute Moderate Ischaemic Stroke (RICAMIS) study. This prespecified exploratory analysis aimed to determine whether there was a difference of RIC efficacy in anterior versus posterior circulation stroke based on RICAMIS data. METHODS: In this analysis, eligible patients presenting within 48 h of stroke onset were divided into two groups: anterior circulation stroke (ACS) and posterior circulation stroke (PCS) groups. The primary endpoint was an excellent functional outcome, defined as a modified Rankin Scale (mRS) score 0-1 at 90 days. RESULTS: In all, 1013 patients were included in the final analysis, including 642 with ACS and 371 with PCS. Compared with the control group, RIC was significantly associated with an increased proportion of mRS scores 0-1 within 90 days in the PCS group (unadjusted odds ratio 1.6, 95% confidence interval 1.0-2.4, p = 0.04; adjusted odds ratio 2.0, 95% confidence interval 1.2-3.3, p = 0.005), but not in the ACS group (p = 0.29). Similar results were found regarding secondary outcomes including mRS score 0-2 at 90 days, mRS distribution at 90 days and change in National Institutes of Health Stroke Scale score at day 12 from baseline. However, there was no significant interaction effect between stroke location and intervention on the primary outcome (pinteraction = 0.21). CONCLUSION: Amongst patients with acute PCS who are not candidates for reperfusion treatment, RIC may be associated with a higher probability of improved functional outcomes. These findings need to be validated in prospective trials.

Balloon Angioplasty vs Medical Management for Intracranial Artery Stenosis: The BASIS Randomized Clinical Trial.

Importance: Previous randomized clinical trials did not demonstrate the superiority of endovascular stenting over aggressive medical management for patients with symptomatic intracranial atherosclerotic stenosis (sICAS). However, balloon angioplasty has not been investigated in a randomized clinical trial. Objective: To determine whether balloon angioplasty plus aggressive medical management is superior to aggressive medical management alone for patients with sICAS. Design, Setting, and Participants: A randomized, open-label, blinded end point clinical trial at 31 centers across China. Eligible patients aged 35 to 80 years with sICAS defined as recent transient ischemic attack (<90 days) or ischemic stroke (14-90 days) before enrollment attributed to a 70% to 99% atherosclerotic stenosis of a major intracranial artery receiving treatment with at least 1 antithrombotic drug and/or standard risk factor management were recruited between November 8, 2018, and April 2, 2022 (final follow-up: April 3, 2023). Interventions: Submaximal balloon angioplasty plus aggressive medical management (n = 249) or aggressive medical management alone (n = 252). Aggressive medical management included dual antiplatelet therapy for the first 90 days and risk factor control. Main Outcomes and Measures: The primary outcome was a composite of any stroke or death within 30 days after enrollment or after balloon angioplasty of the qualifying lesion or any ischemic stroke in the qualifying artery territory or revascularization of the qualifying artery after 30 days through 12 months after enrollment. Results: Among 512 randomized patients, 501 were confirmed eligible (mean age, 58.0 years; 158 [31.5%] women) and completed the trial. The incidence of the primary outcome was lower in the balloon angioplasty group than the medical management group (4.4% vs 13.5%; hazard ratio, 0.32 [95% CI, 0.16-0.63]; P < .001). The respective rates of any stroke or all-cause death within 30 days were 3.2% and 1.6%. Beyond 30 days through 1 year after enrollment, the rates of any ischemic stroke in the qualifying artery territory were 0.4% and 7.5%, respectively, and revascularization of the qualifying artery occurred in 1.2% and 8.3%, respectively. The rate of symptomatic intracranial hemorrhage in the balloon angioplasty and medical management groups was 1.2% and 0.4%, respectively. In the balloon angioplasty group, procedural complications occurred in 17.4% of patients and arterial dissection occurred in 14.5% of patients. Conclusions and Relevance: In patients with sICAS, balloon angioplasty plus aggressive medical management, compared with aggressive medical management alone, statistically significantly lowered the risk of a composite outcome of any stroke or death within 30 days or an ischemic stroke or revascularization of the qualifying artery after 30 days through 12 months. The findings suggest that balloon angioplasty plus aggressive medical management may be an effective treatment for sICAS, although the risk of stroke or death within 30 days of balloon angioplasty should be considered in clinical practice. Trial Registration: ClinicalTrials.gov Identifier: NCT03703635.

Rates and Impact of Serious Adverse Events after Endovascular Thrombectomy among Large Vessel Occlusion Stroke Patients.

OBJECTIVE: Complications or serious adverse events (SAEs) are common in the treatment of patients with large vessel occlusion stroke. There has been limited study of the impact of SAEs for patients after endovascular thrombectomy (EVT). The goal of this study was to characterize the rates and clinical impact of SAEs following EVT. METHODS: A post hoc analysis was performed using pooled databases of the "DEVT" and "RESCUE BT" trials. SAEs were designated as symptomatic intracranial hemorrhage, brain herniation or craniectomy, respiratory failure, circulatory failure, pneumonia, deep venous thrombosis, and systemic bleeding. The primary endpoint was functional independence (modified Rankin scale score 0-2 within 90 days). Logistic regression analysis was used to determine the predictors and associations between SAEs and outcomes. RESULTS: Of 1,182 enrolled patients, 402 (34%) had a procedural complication and 745 (63%) had 1,404 SAE occurrences with 4.65% in-hospital mortality. The three most frequent SAEs were pneumonia (620, 52.5%), systemic bleeding (174, 14.7%), and respiratory failure (173, 14.6%). Pneumonia, systemic bleeding, or deep venous thrombosis was less life-threatening. Patients with advanced age (adjusted odds ratio, 1.28 [95% confidence interval, 1.14-1.43]), higher NIHSS (1.09 [1.06-1.11]), occlusion site (middle cerebral artery-M1 vs. internal carotid artery [ICA]: 0.75 [0.53-1.04]; M2 vs. ICA: 1.30 [0.80-2.12]), longer procedure time (1.01 [1.00-1.01]), and unsuccessful vessel recanalization (1.79 [1.06-2.94]) were more likely to experience SAEs. Compared with no SAE, patients with SAEs had lower odds of functional independence (0.46 [0.40-0.54]). CONCLUSIONS: Overall, SAEs diagnosed following thrombectomy in patients with stroke were common (more than 60%) and associated with functional dependence. Patients with advanced age, higher NIHSS, longer procedure time, and failed recanalization were more likely to experience SAEs. There was no statistical difference in the risk of SAEs among patients with M1 and M2 occluded compared with those ICA occluded. An understanding of the prevalence and predictors of SAEs could alert clinicians to the estimated risk of an SAE for a patient after EVT.

Emerging Adjuvant Thrombolytic Therapies for Acute Ischemic Stroke Reperfusion.

Thrombolytic therapies for acute ischemic stroke are widely available but only result in recanalization early enough, to be therapeutically useful, in 10% to 30% of cases. This large gap in treatment effectiveness could be filled by novel therapies that can increase the effectiveness of thrombus clearance without significantly increasing the risk of harm. This focused update will describe the current state of emerging adjuvant treatments for acute ischemic stroke reperfusion. We focus on new treatments that are designed to (1) target different components that make up a stroke thrombus, (2) enhance endogenous fibrinolytic systems, (3) reduce stagnant blood flow, and (4) improve recanalization of distal thrombi and postendovascular thrombectomy.

Trends in performance of thrombectomy for acute ischemic stroke patients in teaching and non-teaching hospitals.

OBJECTIVES: The value of thrombectomy in patients with acute ischemic stroke cannot be understated. As such, whether these patients get access to this treatment can significantly impact their disease outcomes. We analyzed the trends in thrombectomy adoption between teaching and non-teaching hospitals in the United States, and their impact on overall patient care. MATERIALS AND METHODS: We conducted a retrospective analysis of hospital admissions in the Nationwide Inpatient Sample with a diagnosis of acute ischemic stroke between 2012 and 2020. We compared the annual total number and proportion of patients undergoing thrombectomy between teaching and non-teaching hospitals, and their corresponding outcomes. RESULTS: A total of 3,823,490 and 1,875,705 patients were admitted to teaching and non-teaching hospitals during the study duration, respectively. The proportion of patients who underwent thrombectomy increased from 1.60 % to 7.02 % (p-value for trend p < 0.001) in teaching hospitals and from 0.32 % to 2.20 % (p-value trend p < 0.001) in non-teaching hospitals. The absolute increase in the number of acute ischemic stroke patients undergoing thrombectomy was highest in teaching hospitals particularly those with large bed size, an increase from 3635 patients in 2012 to 24,730 patients in 2020. Higher rates of intravenous thrombolysis and patient transfer prior to thrombectomy were seen in teaching hospitals compared with non-teaching hospitals. CONCLUSIONS: The study highlights disparities between teaching and non-teaching hospitals, with teaching hospitals showing a disproportionately higher rate of thrombectomy adoption in acute ischemic stroke patients. Further studies are needed to understand the barriers to the adoption of thrombectomy in non-teaching hospitals.

Endovascular vs Medical Management of Acute Basilar Artery Occlusion: A Secondary Analysis of a Randomized Clinical Trial.

Importance: In several randomized clinical trials, endovascular thrombectomy led to better functional outcomes than conventional treatment at 90 days poststroke in patients with acute basilar artery occlusion. However, the long-term clinical outcomes of these patients have not been well delineated. Objective: To evaluate 1-year clinical outcomes in patients with acute basilar artery occlusion following endovascular thrombectomy vs control. Design, Setting, and Participants: This study is an extension of the ATTENTION trial, a multicenter, randomized clinical trial. Patients were included between February 2021 and January 2022, with 1-year follow-up through April 2023. This multicenter, population-based study was conducted at 36 comprehensive stroke sites. Patients with acute basilar artery occlusion within 12 hours of estimated symptom onset were included. Of the 342 patients randomized in the ATTENTION trial, 330 (96.5%) had 1-year follow-up information available. Exposures: Endovascular thrombectomy (thrombectomy group) vs best medical treatment (control group). Main Outcomes and Measures: The primary outcome was defined as a score of 0 to 3 on the modified Rankin Scale (mRS) at 1 year. Secondary outcomes were functional independence (mRS score 0-2), excellent outcome (mRS score 0-1), level of disability (distribution of all 7 mRS scores), mortality, and health-related quality of life at 1 year. Results: Among 330 patients who had 1-year follow-up data, 227 (68.8%) were male, and the mean (SD) age was 67.0 (10.7) years. An mRS score 0 to 3 at 1 year was achieved by 99 of 222 patients (44.6%) in the thrombectomy group and 21 of 108 (19.4%) in the control group (adjusted rate ratio, 2.23; 95% CI, 1.51-3.29). Mortality at 1 year compared with 90 days was more frequent in both the thrombectomy group (101 of 222 [45.5%] vs 83 of 226 [36.7%]) and the control group (69 of 108 [63.9%] vs 63 of 114 [55.3%]). Excellent outcome (mRS score 0-1) at 1 year compared with 90 days increased in the thrombectomy group (62 of 222 [27.9%] vs 45 of 226 [19.9%]) but not in the control group (9 of 108 [8.3%] vs 9 of 114 [7.9%]) resulting in a magnified treatment benefit. Conclusions and Relevance: Among patients with basilar artery occlusion within 12 hours of onset, the benefits of endovascular thrombectomy at 1 year compared with 90 days were sustained for favorable (mRS score 0-3) outcome and enhanced for excellent (mRS score 0-1) outcome.

Intravenous thrombolysis versus dual antiplatelet therapy in minor ischemic stroke within the thrombolytic window (TAMIS): a multicenter cohort study.

Intravenous thrombolysis (IVT) and dual antiplatelet therapy (DAPT) have been widely used in minor ischemic stroke (MIS) treatment. However, the clinical outcomes and safety of these two treatments have not been compared within the early thrombolytic time window. Here, we conducted a multicenter, ambispective cohort study involving patients with MIS presenting within 4.5 h of symptom onset at 3 affiliated hospitals of Jinan University from 2018-2022. The patients were divided into the IVT group and DAPT group. The primary outcome was a 90-day excellent outcome (mRS ≤ 1). A total of 1,026 patients were enrolled, of whom 492 were assigned to the IVT group and 534 were assigned to the DAPT group. The IVT group had better 90-day excellent outcomes (mRS ≤ 1) than the DAPT group (OR 1.69, 95% CI 1.14-2.52, P = 0.010). Among the 623 patients with nondisabling stroke, the proportion of mRS ≤ 1 in the IVT group was higher than the DAPT group (P = 0.009). In the subtypes of MIS with large vessel occlusion/stenosis and with isolated symptoms, the 90-day outcomes of the IVT group and DAPT group were not different (P > 0.05). In conclusion, compared with DAPT, IVT was associated with better 90-day clinical outcomes in patients with MIS (in particular, for those with mRS > 1), including earlier clinical improvement.IVT also benefited the early neurological improvement of patients with severe stenosis/occlusion of intracranial large vessels, nondisabling mild stroke, nondisabling mild stroke with isolated symptoms.

Venous sinus stenting under conscious sedation.

BACKGROUND: Venous sinus stenting (VSS) is an increasingly performed procedure for the treatment of idiopathic intracranial hypertension (IIH) refractory to medical treatment. VSS is typically performed under general anesthesia. OBJECTIVE: To present our experience of VSS in patients with IIH performed under conscious sedation. METHODS: Retrospective review of a prospectively maintained database of all patients with IIH who underwent VSS in a single center between September 2019 and January 2024. The sedation protocol consisted of a remifentanil-based target-controlled infusion. Patients' clinical and radiological data, dosage of anesthesia, procedural characteristics, and outcomes were collected. RESULTS: Twenty-six patients with IIH underwent venous manometry (VM) and VSS under awake sedation and were included in our study. Patients were predominantly women (24/26) with a median age (IQR) of 33 (13) years. The median (IQR) body mass index was 34 (10) kg/m2. There was no need for general anesthesia conversion. Technical success was achieved in all patients. Median (IQR) follow-up after stenting was 7 (2) months. All patients reported resolution of the pulsatile tinnitus; headaches regressed in 20/24 (83.3%) patients and papilledema improved in 16/20 (80%). Only one non-neurological complication (retroperitoneal hematoma) occurred, without any permanent morbidity or mortality. CONCLUSION: Our study confirms that performing VM and VSS under conscious sedation is safe and feasible. Conscious sedation is a viable alternative to general anesthesia for managing IIH in these patients.

REACT: a randomized trial to assess the efficacy and safety of clazosentan for preventing clinical deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Ischemic complications account for significant patient morbidity following aneurysmal subarachnoid hemorrhage (aSAH). The Prevention and Treatment of Vasospasm with Clazosentan (REACT) study was designed to assess the safety and efficacy of clazosentan, an endothelin receptor antagonist, in preventing clinical deterioration due to delayed cerebral ischemia (DCI) in patients with aSAH. METHODS: REACT was a prospective, multicenter, randomized, double-blind, phase 3 study. Eligible patients had aSAH secured by surgical clipping or endovascular coiling, and had presented with thick and diffuse clot on admission CT scan. Patients were randomized (1:1 ratio) to 15 mg/hour intravenous clazosentan or placebo within 96 hours of the aSAH for up to 14 days, in addition to standard of care treatment including oral or intravenous nimodipine. The primary efficacy endpoint was the occurrence of clinical deterioration due to DCI up to 14 days after initiation of the study drug. The main secondary endpoint was the occurrence of clinically relevant cerebral infarction at day 16 after study drug initiation. Other secondary endpoints included clinical outcome assessed on the modified Rankin Scale (mRS) and the Glasgow Outcome Scale-Extended (GOSE) at week 12 post-aSAH. Imaging and clinical endpoints were centrally adjudicated. RESULTS: A total of 409 patients were randomized between February 2019 and May 2022 across 74 international sites. Three patients did not start study treatment and were not included in the analysis set. The occurrence of clinical deterioration due to DCI was 15.8% (32/202 patients) in the clazosentan group and 17.2% (35/204 patients) in the placebo group, and the difference was not statistically significant (relative risk reduction [RRR] 7.2%, 95% CI -42.6% to 39.6%, p = 0.734). A nonsignificant RRR of 34.1% (95% CI -21.3% to 64.2%, p = 0.177) was observed in clinically relevant cerebral infarcts treated with clazosentan (7.4%, 15/202) versus placebo (11.3%, 23/204). Rescue therapy was less frequently needed for patients treated with clazosentan compared to placebo (10.4%, 21/202 vs 18.1%, 37/204; RRR 42.6%, 95% CI 5.4%-65.2%). A nonsignificant relative risk increase of 25.4% (95% CI -10.7% to 76.0%, p = 0.198) was reported in the risk of poor GOSE and mRS scores with clazosentan (24.8%, 50/202) versus placebo (20.1%, 41/204) at week 12 post-aSAH. Treatment-emergent adverse events were similar to those reported previously. CONCLUSIONS: Clazosentan administered for up to 14 days at 15 mg/hour had no significant effect on the occurrence of clinical deterioration due to DCI. Clinical trial registration no.: NCT03585270 (ClinicalTrials.gov) EU clinical trial registration no.: 2018-000241-39 (clinicaltrialsregister.eu).