Endovascular thrombectomy with or without intravenous alteplase in large-core ischemic stroke: a systematic review and meta-analysis.

The role of bridging intravenous thrombolysis (IVT) with alteplase before endovascular thrombectomy (EVT) in treating large core ischemic stroke remains uncertain. We aimed to compare clinical outcomes and safety of EVT with or without bridging IVT in patients with anterior circulation large vessel occlusion (ACLVO) and baseline Alberta Stroke Program Early CT Score (ASPECTS) ≤ 5. We systematically searched PubMed, Web of Science, Cochrane Library, and Embase from inception until November 2023. The primary outcome was 90-day functional independence (modified Rankin Scale [mRS] 0-2). Secondary outcomes included 90-day independent ambulation (mRS 0-3), successful recanalization, any intracranial hemorrhage (ICH), symptomatic ICH (sICH) and 90-day mortality. A random-effects model was used for data pooling. Five high-quality studies, incorporating 2124 patients (41% treated with bridging IVT), were included. Across both unadjusted and adjusted analyses, no significant differences were found between the bridging IVT and EVT-alone groups in terms of functional independence (odds ratios [OR] = 1.36, 95% confidence interval [CI]: 0.90-2.07, P = 0.14; adjusted OR [aOR] = 1.19, 95% CI: 0.68-2.09, P = 0.53) or independent ambulation (OR = 1.14, 95% CI: 0.80-1.62, P = 0.47; aOR = 1.18, 95% CI: 1.00-1.39, P = 0.05) at 90 days. Furthermore, no differences were observed in successful recanalization, any ICH, sICH, and 90-day mortality between the two treatment groups. Bridging IVT exhibits similar functional and safety outcomes compared to EVT alone in ACLVO patients with baseline ASPECTS ≤ 5. Further research is warranted to confirm these findings.

Risk Factors for Severe Residual Headache in Cerebral Venous Thrombosis.

BACKGROUND AND PURPOSE: Which factors will influence the presence of severe residual headache after cerebral venous thrombosis (CVT) is unclear. The purpose of this study was to identify risk factors for severe residual headache in a large single-center cohort of patients with CVT. METHODS: We consecutively included eligible patients with CVT from a prospective stroke registry. Severe residual headache was defined as a residual headache attack requiring bed rest or hospital admission within 1 month before the last follow-up visit. We identified the risk factors of severe residual headache in all survivors and in those with favorable functional outcome (a modified Rankin Scale score, 0-2). RESULTS: A total of 325 patients' data were analyzed. At the last follow-up (median 13 months), 43 patients (13.2%) reported severe headache. In the multivariable analysis, isolated intracranial hypertension (odds ratio [OR], 3.309 [95% CI, 1.434-7.634]; P=0.005), CVT recurrence (OR, 4.722 [95% CI, 1.639-13.602]; P=0.004), and no recanalization (OR, 10.158 [95% CI, 4.194-24.600]; P<0.001) were independently associated with severe headache. Severe headache was more frequent in patients with unfavorable outcome (11/25 [44.0%] versus 32/300 [10.7%]; P<0.001). In patients with favorable outcome, the risk factors for severe headache were isolated intracranial hypertension (OR, 3.236 [95% CI, 1.268-8.256]; P=0.014) and no recanalization (OR, 7.863 [95% CI, 3.120-19.812]; P<0.001). CONCLUSIONS: Isolated intracranial hypertension, CVT recurrence, and no recanalization increased the risk for severe residual headache after CVT.

Low-Dose Tissue Plasminogen Activator in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Intravenous thrombolysis using tissue plasminogen activator (tPA) improves significantly the neurologic function in patients with acute ischemic stroke (AIS). However, it brings financial burden to patients and is associated with symptomatic intracranial hemorrhage (SICH). Whether low-dose tPA can effectively reduce SICH and has the same efficacy as standard-dose tPA is still controversial. METHODS: We searched for English clinical trials published before March, 2017on the comparison of the efficacy and safety between low and standard dose of tPA in the treatment of AIS using MEDLINE, Embase, and Cochrane Library. The modified Rankin scale (mRS) score was used as the primary efficacy outcome. The mRS1 corresponded to 0-1, whereas mRS2 corresponded to 0-2. The SICH and mortality were adopted as primary safety outcomes. RESULTS: Twelve high-quality studies were selected, including 7686 patients (low-dose: 2888, standard-dose: 4798). With no statistical heterogeneity, the fixed effects model was adopted in the analysis. Similarly to standard doses, low-dose tPA improved the mRS scores (mRS1: odds ratio [OR] = .92, 95% confidence interval [CI] .84-1.02; P = .12; mRS2: OR = .97, 95% CI .88-1.08; P = .57). Compared with standard-dose tPA, low-dose tPA reduced the incidence of SICH (by National Institute of Neurological Disorders and Stroke [NINDS] definition: OR = .71, 95% CI .57-0.89; P = .003; by Safe Implementation of Thrombolysis in Stroke Monitoring Study [SITS-MOST] definition: OR = .64, 95% CI .42-0.99; P = .04), while both reduced mortality (OR = .87, 95% CI .74-1.02; P = .08). CONCLUSIONS: Low-dose tPA is comparable to standard-dose tPA in improving the neurologic function and reducing mortality in AIS patients. Moreover, low-dose tPA can reduce the incidence of SICH compared with standard-dose tPA. Therefore, low-dose tPA is highly recommended in AIS patients.

CBF Profile in Computed Tomography Perfusion-Based AutoMIStar Software Predicts Futile Recanalization After Basilar Artery Thrombectomy.

Background: Futile recanalization (FR) remains a significant challenge in patients with acute basilar artery occlusion (BAO) following successful endovascular treatment (EVT). This study aimed to investigate the predictive value of computed tomography perfusion (CTP)-based software (AutoMIStar; Apollo) for FR among BAO patients undergoing EVT. Methods: We analyzed a prospectively maintained database to identify consecutive BAO patients who achieved successful recanalization (modified Thrombolysis in Cerebral Infarction grade ≥ 2b) after EVT between January 2020 and September 2022. Clinical characteristics and imaging parameters from non-contrast CT, CT angiography, and CTP-AutoMIStar were collected for analysis. FR was defined as an unfavorable outcome (modified Rankin Scale score > 3) at 90 days despite successful recanalization. Multivariable stepwise logistic regression analysis was performed to identify independent predictors of FR. Results: Of the 54 patients included in this study, 24 (44.4%) experienced FR. In the univariate analysis, admission National Institutes of Health Stroke Scale score, posterior circulation Acute Stroke Prognosis Early CT Score, Basilar Artery on Computed Tomography Angiography (BATMAN) score, hypoperfusion intensity ratio, and perfusion deficit volume in delay time (DT) > 4 s, DT > 6 s, DT > 8 s, and all cerebral blood flow (CBF) thresholds were associated with FR (all P < 0.05). In the multivariate analysis, perfusion deficit volume in CBF < 35% (adjusted odds ratio [aOR] = 1.105, 95% confidence interval [CI]: 1.004-1.215; P = 0.040) and BATMAN score (aOR = 0.662, 95% CI: 0.455-0.964; P = 0.031) remained independent predictors of FR. Conclusion: Perfusion deficit volume in CBF < 35% on CTP-AutoMIStar imaging maps and BATMAN score are independent predictors of FR after EVT in BAO patients. There is a significant positive correlation between perfusion deficit volume in CBF < 35% and the occurrence of FR.

Low-dose vs. standard-dose intravenous alteplase for acute ischemic stroke with unknown time of onset.

Background: Standard-dose intravenous alteplase for acute ischemic stroke (AIS) in the unknown or extended time window beyond 4.5 h after symptom onset is both effective and safe for certain patients who were selected based on multimodal neuroimaging. However, uncertainty exists regarding the potential benefit of using low-dose alteplase among the Asian population outside the 4.5-h time window. Methods: Consecutive AIS patients who received intravenous alteplase between 4.5 and 9 h after symptom onset or with an unknown time of onset guided by multimodal computed tomography (CT) imaging were identified from our prospectively maintained database. The primary outcome was excellent functional recovery, defined as having a modified Rankin scale (mRS) score of 0-1 at 90 days. Secondary outcomes included functional independence (an mRS score of 0-2 at 90 days), early major neurologic improvement (ENI), early neurologic deterioration (END), any intracranial hemorrhage (ICH), symptomatic ICH (sICH), and 90-day mortality. Propensity score matching (PSM) and multivariable logistic regression models were used to adjust for confounding factors and compare the clinical outcomes between the low- and standard-dose groups. Results: From June 2019 to June 2022, a total of 206 patients were included in the final analysis, of which 143 were treated with low-dose alteplase and 63 were treated with standard-dose alteplase. After accounting for confounding factors, we observed that there were no statistically significant differences between the standard- and low-dose groups with respect to excellent functional recovery [adjusted odds ratio = 1.22 (aOR), 95% confidence interval (CI): 0.62-2.39; adjusted rate difference (aRD) = 4.6%, and 95% CI: -11.2 to 20.3%]. Patients of both groups had similar rates of functional independence, ENI, END, any ICH, sICH, and 90-day mortality. In the subgroup analysis, patients aged ≥70 years were more likely to achieve excellent functional recovery when receiving standard-dose rather than low-dose alteplase. Conclusion: The effectiveness of low-dose alteplase might be comparable to that of standard-dose alteplase in AIS patients aged <70 years with favorable perfusion-imaging profiles in the unknown or extended time window but not in those aged ≥70 years. Furthermore, low-dose alteplase did not significantly reduce the risk of sICH compared to standard-dose alteplase.

Emergency Angioplasty or Stenting for Stroke Patients with Intracranial Atherosclerotic Large Vessel Occlusion.

AIM: Mechanical thrombectomy (MT) has become the gold standard for the treatment of large vessel occlusion (LVO) in acute ischemic stroke. However, it remains controversial whether emergency angioplasty or stenting in patients with intracranial atherosclerotic stenosis (ICAS) should be adopted. Thus, we performed a retrospective analysis of clinical data to determine whether emergency angioplasty or stenting is necessary. METHODS: We retrospectively analyzed data from patients undergoing MT with ICAS-related LVO of the acute anterior circulation between 2017 and 2019. Eligible patients were divided into two treatment groups: those who received rescue angioplasty or stenting [Patients treated with rescue angioplasty or stenting (PTAS) group] and those who received thrombectomy alone (non-PTAS group). The primary outcomes were good prognosis at 90 days (mRS: 0-2). Mortality, symptomatic intracranial hemorrhage, and reocclusion rate were evaluated as secondary outcomes. RESULTS: A total of 184 patients with severe stenosis after MT were enrolled, including 64 patients receiving rescue angioplasty or stenting and 120 patients without rescue angioplasty or stenting. Compared with the non-PTAS group, a better functional outcome (mRS0-2) (51.6% vs. 35.0%, adjusted odds ratio: 2.11, 95% confidence interval [CI]: 1.22-4.29; P=0.02), lower 7-day National Institutes of Health Stroke Scale [6 (3-12.75) vs. 10 (4-16); P=0.04], lower 24-h neurological deterioration rate (7.8% vs. 21.7%, P=0.02), and lower 24-h reocclusion rate were observed in the PTAS group (6.3% vs. 17.5%, P=0.03). There were no significant differences in mortality or incidence of symptomatic intracerebral hemorrhage. CONCLUSION: Emergency angioplasty or stenting could be a safe and feasible therapeutic option with better outcomes for stroke patients with ICAS-related LVO.

Normobaric Hyperoxia Combined With Endovascular Treatment for Patients With Acute Ischemic Stroke: A Randomized Controlled Clinical Trial.

BACKGROUND AND OBJECTIVES: To investigate the safety and efficacy of normobaric hyperoxia (NBO) combined with endovascular treatment (EVT) in patients with acute ischemic stroke (AIS). METHODS: In this single-center, proof-of-concept, assessor-blinded, randomized, controlled pilot study, patients with AIS in the acute anterior circulation with large vessel occlusion who had an indication for EVT were randomly assigned to the EVT group or the NBO + EVT group. The NBO + EVT group was given 100% oxygen through a face mask initiated before vascular recanalization (10L/min for 4 hours), while the EVT group was given room air. The primary endpoint was infarct volume measured by MRI within 24-48 hours after randomization. RESULTS: A total of 231 patients were screened, and 86 patients were randomized into a ratio of 1:1 (EVT group, n = 43; NBO + EVT group, n = 43). The median infarction volume of the NBO + EVT group at 24-48 hours after randomization was significantly smaller than that of the EVT group (median 20.1 vs 37.7 mL, p < 0.01). The median mRS score at 90 days was 2 for the NBO + EVT group when compared with 3 for the EVT group (adjusted value 1.8, 95% CI 1.3-4.2; p = 0.038). Compared with the EVT group, the NBO + EVT group had a lower incidence of symptomatic intracranial hemorrhagic (7% vs 12%), mortality (9% vs 16%), and adverse events (33% vs 42%); however, such a difference was not statistically significant. DISCUSSION: NBO in combination with EVT seems to be a safe and feasible treatment strategy that could significantly reduce infarct volume, improve short-term neurobehavioral test score, and enhance clinical outcomes at 90 days when compared with EVT alone in patients with AIS. These observations need to be further confirmed by a large, multicenter, randomized clinical trial. CLINICAL TRIALS REGISTRATION: NCT03620370. CLASSIFICATION OF EVIDENCE: This pilot study provides Class I evidence that NBO combined with standard EVT decreases infarction volume in patients with acute anterior circulation stroke.

Long-term outcome of endovascular therapy for acute basilar artery occlusion.

The long-term functional outcome of acute basilar artery occlusion (BAO) patients who received modern endovascular therapy (EVT) is unclear. We sought to assess the long-term functional outcome of BAO patients treated with EVT and determine the prognostic factors associated with favorable outcome. We enrolled consecutive BAO patients who received EVT between December 2012 and December 2018 in this observational study. Baseline characteristics and outcomes were presented. Multivariable logistic regression analysis was performed to identify the prognostic factors associated with long-term outcome. Among the 177 BAO patients included in this study, 80 patients (45.2%) obtained favorable outcome and 97 patients (54.8%) had unfavorable outcome at long-term follow-up with a median observation time of 12 months (interquartile range, 3-19). A total of 67 patients (37.9%) died. National Institutes of Health Stroke Scale (NIHSS), posterior circulation Alberta Stroke Program Early Computed Tomography Score (pc-ASPECTS), time from stroke onset to recanalization, and recanalization condition were identified as independent predictors for long-term outcome. Over 40% of BAO patients who were treated with modern EVT achieved favorable outcome at long-term follow-up. NIHSS, pc-ASPECTS, time from stroke onset to recanalization, and recanalization condition were identified as independent prognostic factors of long-term outcome.

Prognosis and risk factors for reocclusion after mechanical thrombectomy.

OBJECTIVE: This study evaluates reocclusion prognostic outcomes and explores reocclusion risk factors after mechanical thrombectomy (MT) in Chinese stroke patients. METHODS: Altogether, 614 patients with AIS with successful recanalization after MT were recruited in this study and divided into the reocclusion and the non-reocclusion group depending on the 24-h imaging results after MT. Differences between the two groups were compared including 24-h and 7-day National Institutes of Health Stroke Scale (NIHSS) scores, 90-day modified Rankin scale(mRS) scores, good prognosis (mRS:0-2) rates, incidence of intracranial hemorrhage, and 90-day mortality. RESULTS: Forty-four (7.2%) patients experienced reocclusion within 24 h. Compared with the non-reocclusion group, patients in the reocclusion group had higher 24-h (15 vs. 13) and 7-day (15 vs. 9) NIHSS scores, 90-day mRS scores (4 vs. 3), and 90-day mortality rates (34.1% vs. 18.6%); lower rates of good prognosis (13.6% vs. 9.3%); and a higher incidence of early neurological deterioration (36.4% vs. 14.7%). Age, internal carotid artery occlusion (ICA), intravenous thrombolysis (IVT), number of thrombectomy passes, stent implantation, and levels of D-dimer (adjusted odds ratio and 95% confidence interval: 0.97, 0.94-0.99; 2.40, 1.10-5.23; 2.21, 1.05-4.66; 2.60, 1.04-6.47; 0.25, 0.09-0.67; and 1.06, 1.01-1.12, respectively) were independently associated with 24-h reocclusion. INTERPRETATION: The prognosis of reocclusion after MT was poor. Timely evaluation of these factors including age, D-dimer, ICA occlusion, IVT, number of passes, and stent implantation and appropriate intervention could reduce the incidence of reocclusion for Chinese stroke patients.

Local anesthesia vs general anesthesia during endovascular therapy for acute posterior circulation stroke.

OBJECTIVE: The optimal anesthetic approach during endovascular therapy (EVT) in acute stroke patients remains an area of uncertainty. We investigated the impact of different anesthetic approaches on the outcome of posterior circulation stroke (PCS) patients undergoing EVT. METHODS: For this observational study, we enrolled consecutive PCS patients who underwent EVT from December 2012 to December 2018, and compared functional outcomes at 90 days as well as long-term follow-up in patients treated under local anesthesia (LA) versus general anesthesia (GA). Multivariable logistic regression and propensity score matched analyses were conducted. RESULTS: Among the 183 patients included in this study, 71 patients (38.8%) received LA and 112 patients (61.2%) received GA. Median modified Rankin Scale score at 90 days was 4 (IQR, 2-6) in both groups (P = .956). No significant differences in the rates of functional independence and mortality at 90 days as well as long-term follow-up post intervention were observed between the two groups, and Kaplan-Meier survival analysis showed comparable long-term survival probabilities. Safety outcomes (including procedure-related complications and serious adverse events) did not differ between these patients. The anesthetic approach was neither associated with functional independence nor associated with mortality. Propensity score matched analysis indicated similar results. CONCLUSIONS: For PCS patients undergoing EVT, LA compared with GA does not seem to result in different functional outcomes and complications rates.

Anticoagulation delay does not affect the functional outcome of cerebral venous thrombosis.

Available knowledge about the impact of anticoagulation delay on outcomes of patients with cerebral venous thrombosis (CVT) is limited. We therefore assessed the factors influencing anticoagulation delay and investigated the effect of this delay on outcomes of CVT patients. Anticoagulation delay was defined as the time interval between symptom onset and anticoagulation initiation. The primary outcome was a modified Rankin Scale (mRS) score > 2 at the final follow-up. A total of 164 eligible patients were included. The median anticoagulation delay was 9 days. Cerebral hemorrhage on admission neuroimaging correlated with earlier anticoagulation (p = 0.040). Anticoagulation delay was not associated with poor functional outcome (mRS > 2), but it was associated with residual headache across the entire cohort (earlier anticoagulation: 15/76 [19.7%] vs. later anticoagulation: 28/79 [35.4%]; p = 0.029) and in the subgroup with isolated intracranial hypertension (earlier anticoagulation: 4/25 [16.0%] vs. later anticoagulation: 14/27 [51.9%]; p = 0.007). Anticoagulation delay was found to be common among patients with CVT. Anticoagulation delay was not associated with poor functional outcome, but may have led to an increased risk of residual headache across our entire cohort and in the subgroup with isolated intracranial hypertension.

Long-term Outcomes of Cerebral Venous Sinus Stenosis Corrected by Stenting.

BACKGROUND AND PURPOSE: Cerebral Venous Sinus Stenosis (CVSS) usually results in severe Intracranial Hypertension (IH), which can be corrected by stenting immediately. However, there is a lack of evidence of the long-term good outcomes in patients with CVSS who underwent stenting. METHODS: A total of 62 patients with imaging confirmed non-thrombotic and non-external compression CVSS were enrolled into this single center real-world cohort study after undergoing stenting, and were continuously followed up for more than 12 years. The symptoms and signs of IH prior to stenting and post-stenting and the incidence of restenosis after stenting were analyzed. RESULTS: The mean age of the 62 patients (range, 13 to 62) was 40 years old, and the mean body mass index was 26 (range 23 to 40). Females accounted for 67.7% (42/62). Headache was the most common symptom (79%). Transient visual obscurations occurred in 69% of the patients. 42% of the patients suffered from visual loss, 11.3% pulsatile tinnitus, and 96.8% Papilledema before stenting. The mean trans-stenotic pressure gradients were 6~43 mmHg prior to stenting and returned to 0~4 mmHg after stent placement. During the following 12~126 months (the median was 62) after stenting of the follow-up, 91.9% (57/62) of the patients obtained good outcomes. Headaches disappeared in 96% (47/49) of the patients and papilledema was attenuated in 98.3% (59/60). However, There were still 8.0 % (5/62) of the patients with poor outcomes, including optic disc atrophy in 3 patients and stent-interior thrombosis in 2 patients, which occurred 6.3 months after stenting. CONCLUSION: Our data suggest that stenting may be a promising therapy for CVSS correcting. Patients with CVSS may get long-term benefit from stenting, especially when they are accompanied with severe IH.

Combination of High-Sensitivity C-Reactive Protein and Homocysteine Predicts the Post-Stroke Depression in Patients with Ischemic Stroke.

In this study, we examined the changes in high-sensitivity C-reactive protein (Hs-CRP) and homocysteine (HCY) levels, two of the risk factors, during the acute period of ischemic stroke (IS) and evaluated the relationship between these two factors and long-term post-stroke depression (PSD). In this study, 259 patients with IS had finished the follow-up and were included. Based on the symptoms, diagnoses of depression were made in accordance with DSM-IV criteria for depression at 1 year after stroke. The influence of Hs-CRP/CHY levels on PSD was performed by binary logistic regression analysis and receiver operating characteristic curves (ROC). Totally, 94 out of the 259 patients were diagnosed as PSD (36.3%; 95% CI 30.4-42.1%). In multivariate logistic regression analysis, the third and fourth quartiles of Hs-CRP or HCY were significantly associated with PSD during the observation period compared to the first quartile group (P < 0.05). In addition, patients with depression were older and more frequently were female, living with offspring, widowhood, higher initial stroke severity, and BMI. HCY improved the ability of Hs-CRP [0.72 (95% CI 0.66-0.79)] to diagnose PSD (AUC of the combined model 0.76; 95% CI 0.69-0.82; P = 0.021). The patient group with higher levels of both Hs-CRP and HCY (> median) had an OR of 6.05 (95 % CI 3.13-10.15; P < 0.001) for PSD compared with patients with lower levels of both factors (< median). The data suggests that elevated serum levels of Hs-CRP and HCY were associated with the risk of developing PSD 1 year after the stroke onset, and those two factors combined to add prognostic information in the early evaluation of PSD.

Preconditioning of H2S inhalation protects against cerebral ischemia/reperfusion injury by induction of HSP70 through PI3K/Akt/Nrf2 pathway.

It is of great importance to protect the brain against cerebral ischemia and reperfusion (I/R) injury, which leads to excitotoxicity, redox imbalance, inflammation and apoptosis; however, there is currently no effective treatment. The present study aimed to investigate the effect of H2S preconditioning on cerebral I/R injury and its underlying mechanism. The results demonstrated that H2S preconditioning significantly prevented the development of neurological function abnormality, inflammation and oxidative injury in mice as well as cognitive impairment caused by cerebral I/R. H2S preconditioning also suppressed the apoptosis caused by cerebral I/R. Moreover, the protective effect of H2S preconditioning was found to involve heat shock protein 70 (HSP70), in which the PI3K/Akt/Nrf2 pathway was involved. The data showed that H2S preconditioning could protect mice against cerebral I/R injury by the induction of HSP70 and the PI3K/Akt/Nrf2 pathway.