Trial of Thrombectomy 6 to 24 Hours after Stroke Due to Basilar-Artery Occlusion.

BACKGROUND: The effects and risks of endovascular thrombectomy 6 to 24 hours after stroke onset due to basilar-artery occlusion have not been extensively studied. METHODS: In a trial conducted over a 5-year period in China, we randomly assigned, in a 1:1 ratio, patients with basilar-artery stroke who presented between 6 to 24 hours after symptom onset to receive either medical therapy plus thrombectomy or medical therapy only (control). The original primary outcome, a score of 0 to 4 on the modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 4 moderately severe disability, and 6 death) at 90 days, was changed to a good functional status (a modified Rankin scale score of 0 to 3, with a score of 3 indicating moderate disability). Primary safety outcomes were symptomatic intracranial hemorrhage at 24 hours and 90-day mortality. RESULTS: A total of 217 patients (110 in the thrombectomy group and 107 in the control group) were included in the analysis; randomization occurred at a median of 663 minutes after symptom onset. Enrollment was halted at a prespecified interim analysis because of the superiority of thrombectomy. Thrombolysis was used in 14% of the patients in the thrombectomy group and in 21% of those in the control group. A modified Rankin scale score of 0 to 3 (primary outcome) occurred in 51 patients (46%) in the thrombectomy group and in 26 (24%) in the control group (adjusted rate ratio, 1.81; 95% confidence interval [CI], 1.26 to 2.60; P<0.001). The results for the original primary outcome of a modified Rankin scale score of 0 to 4 were 55% and 43%, respectively (adjusted rate ratio, 1.21; 95% CI, 0.95 to 1.54). Symptomatic intracranial hemorrhage occurred in 6 of 102 patients (6%) in the thrombectomy group and in 1 of 88 (1%) in the control group (risk ratio, 5.18; 95% CI, 0.64 to 42.18). Mortality at 90 days was 31% in the thrombectomy group and 42% in the control group (adjusted risk ratio, 0.75; 95% CI, 0.54 to 1.04). Procedural complications occurred in 11% of the patients who underwent thrombectomy. CONCLUSIONS: Among patients with stroke due to basilar-artery occlusion who presented 6 to 24 hours after symptom onset, thrombectomy led to a higher percentage with good functional status at 90 days than medical therapy but was associated with procedural complications and more cerebral hemorrhages. (Funded by the Chinese National Ministry of Science and Technology; BAOCHE ClinicalTrials.gov number, NCT02737189.).

Ticking Brain: Circadian Rhythm as a New Target for Cerebroprotection.

Circadian rhythm is a master process observed in nearly every type of cell throughout the body, and it macroscopically regulates daily physiology. Recent clinical trials have revealed the effects of circadian variation on the incidence, pathophysiological processes, and prognosis of acute ischemic stroke. Furthermore, core clock genes, the cell-autonomous pacemakers of the circadian rhythm, affect the neurovascular unit-composing cells in a nonparallel manner after the same pathophysiological processes of ischemia/reperfusion. In this review, we discuss the influence of circadian rhythms and clock genes on each type of neurovascular unit cell in the pathophysiological processes of acute ischemic stroke.

Remote ischemic conditioning improves cerebral hemodynamics in symptomatic intracranial atherosclerosis: A PET/CT-guided randomized controlled study.

Patients with symptomatic intracranial arterial stenosis (sICAS) suffer embarrassed hemodynamic status and acute ischemic stroke (AIS) recurrence. We aimed to assess the efficacy of remote ischemic conditioning (RIC) on improving this status by evaluating cerebral blood flow (CBF) and cerebral glucose metabolism (CGM) via PET/CT. Adult patients with unilateral sICAS in middle cerebral artery and/or intracranial segment of internal carotid artery-related AIS or transient ischemic attack within 6 months prior to randomization were enrolled. Individuals who received intravenous thrombolysis or endovascular treatment, or sICAS caused by cardiac embolism, small vessel occlusion, or other determined causes were excluded. Twenty-three eligible patients were randomly assigned to standard medical treatment (SMT) (n = 10) or RIC group (n = 13). The RIC protocol consisted of 5 cycles, each for 5-min bilateral upper limb ischemia and 5-min reperfusion period, twice a day, with a total duration of 3 months. Ten healthy volunteers were enrolled as healthy control group. We tested CBF and CGM at the rest stage and the methazolamide-induced stress stage. All patients received PET/CT at baseline and three-month followup. Both CBF and CGM in ipsilateral hemisphere of sICAS patients were significantly decreased at the rest stage and the stress stage (p < .05), which were improved by three-month RIC (p < .05). The lesions decreased notably in RIC group compared to SMT group (p < .05). RIC ameliorated the hemodynamic status and glucose metabolism in regions at high risk of infarction, which might improve the resistance capacity towards ischemic load in sICAS patients.

Advancing stroke therapy: innovative approaches with stem cell-derived extracellular vesicles.

Stroke is a leading cause of mortality and long-term disability globally, with acute ischemic stroke (AIS) being the most common subtype. Despite significant advances in reperfusion therapies, their limited time window and associated risks underscore the necessity for novel treatment strategies. Stem cell-derived extracellular vesicles (EVs) have emerged as a promising therapeutic approach due to their ability to modulate the post-stroke microenvironment and facilitate neuroprotection and neurorestoration. This review synthesizes current research on the therapeutic potential of stem cell-derived EVs in AIS, focusing on their origin, biogenesis, mechanisms of action, and strategies for enhancing their targeting capacity and therapeutic efficacy. Additionally, we explore innovative combination therapies and discuss both the challenges and prospects of EV-based treatments. Our findings reveal that stem cell-derived EVs exhibit diverse therapeutic effects in AIS, such as promoting neuronal survival, diminishing neuroinflammation, protecting the blood-brain barrier, and enhancing angiogenesis and neurogenesis. Various strategies, including targeting modifications and cargo modifications, have been developed to improve the efficacy of EVs. Combining EVs with other treatments, such as reperfusion therapy, stem cell transplantation, nanomedicine, and gut microbiome modulation, holds great promise for improving stroke outcomes. However, challenges such as the heterogeneity of EVs and the need for standardized protocols for EV production and quality control remain to be addressed. Stem cell-derived EVs represent a novel therapeutic avenue for AIS, offering the potential to address the limitations of current treatments. Further research is needed to optimize EV-based therapies and translate their benefits to clinical practice, with an emphasis on ensuring safety, overcoming regulatory hurdles, and enhancing the specificity and efficacy of EV delivery to target tissues.

Normobaric Hyperoxia Combined with Endovascular Treatment in Patients with Acute Ischemic Stroke (OPENS-2) Trial: Protocol for a Prospective, Multicenter, Randomized Controlled Study.

Normobaric hyperoxia (NBO) is a potentially promising stroke treatment strategy that could protect the ischemic penumbra and could be administered as an adjunct before vascular recanalization. However, the efficacy and safety of NBO have not been confirmed by randomized controlled trials. The study aims to assess the efficacy and safety of NBO for ischemic stroke due to large artery occlusion (LVO) of acute anterior circulation among patients who had endovascular treatment (EVT) and were randomized within 6 h from symptom onset. Based on the data of the modified Rankin Scale (mRS) score at 90 days from the normobaric hyperoxia combined with EVT for acute ischemic stroke (OPENS: NCT03620370) trial, 284 patients will be included to achieve a 90% power by using Wilcoxon-Mann-Whitney test and the proportional odds model to calculate the sample size. The study is a prospective, multicenter, blinded, randomized controlled trial. The NBO group is administered with mask oxygen therapy of 10 L/min, while the sham NBO group is with that of 1 L/min. The primary outcome is the mRS score at 90 days. Secondary endpoints include cerebral infarct volume at 24-48 h, functional independence (mRS ≤2) at 90 days, and improvement in neurological function at 24 h. Safety outcomes include 90-day mortality, oxygen-related adverse events, and serious adverse events. This study will indicate whether NBO combined with EVT is superior to EVT alone for acute ischemic stroke caused by LVO in subjects randomized within 6 h from symptom onset and will provide some evidence for NBO intervention as an adjunct to thrombectomy for acute stroke.

A case report: new-onset nummular headache after stenting of the middle cerebral artery.

BACKGROUND: Nummular headache (NH) is categorized as a primary headache in the International Classification of Headache Disorders, Third edition (ICHD-3) diagnostic criteria, but there are secondary etiologies as well. We present a case of secondary NH that associated with vascular lesion. CASE PRESENTATION: We report on a 40-year-old man with a medical history of symptomatic intracranial arterial stenosis who developed a headache after percutaneous transluminal angioplasty and stenting because of Intracranial atherosclerotic stenosis(ICAS). This new-onset headache was a pinprick headache confined to the parietal part of the head and 5 cm in size. This headache most closely resembled the phenotype of a NH. And other causes of secondary headache were excluded. Thus, the diagnosis of NH was highly speculated. This patient represents a rare headache phenomenon after intracranial arterial stent placement. CONCLUSION: This is the first report of NH after stent placement treatment in a patient with ICAS.

Cerebral venous sinus thrombosis associated with JAK2 V617F mutation-related pre-primary myelofibrosis: a case report and literature review.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare but potentially life-threatening subtype of stroke. Prompt and appropriate anticoagulation is crucial for improving the prognosis of CVST and preventing its recurrence. Identifying the underlying cause of CVST is decisive for guiding anticoagulant selection and determining treatment duration. CASE PRESENTATION: A 50-year-old man presented with a 35-day history of headache, nausea, vomiting, and blurred vision. Digital subtraction angiography performed at another facility revealed CVST. A contrast-enhanced black-blood MRI at our center confirmed the diagnosis, which was supported by a high intracranial pressure of 330mmH2O. Laboratory tests showed elevated leukocytes and platelet counts, raising suspicion of an underlying myeloproliferative neoplasms (MPNs). A bone marrow biopsy demonstrated increased megakaryocytes and granulocytes, and genetic testing identified the presence of the Janus kinase 2 V617F (JAK2 V617F) mutation, leading to a diagnosis of pre-primary myelofibrosis (pre-PMF). During hospitalization, anticoagulation with nadroparin calcium and fibrinolytic therapy were initiated. Upon discharge, rivaroxaban and aspirin were prescribed to prevent CVST recurrence and arterial thrombosis. CONCLUSION: This case highlights the importance of recognizing dynamic changes in routine blood tests that may link CVST to underlying hematological disorders. The JAK2 mutation is not only associated with MPNs but also increases the risk of thrombosis, including CVST. Further investigation is warranted to better understand the mechanisms by which JAK2 mutations contribute to thrombosis and to explore the potential benefits of JAK2 inhibitors in reducing this risk.

Performance and Analysis of the Alchemical Transfer Method for Binding-Free-Energy Predictions of Diverse Ligands.

The Alchemical Transfer Method (ATM) is herein validated against the relative binding-free energies (RBFEs) of a diverse set of protein-ligand complexes. We employed a streamlined setup workflow, a bespoke force field, and AToM-OpenMM software to compute the RBFEs of the benchmark set prepared by Schindler and collaborators at Merck KGaA. This benchmark set includes examples of standard small R-group ligand modifications as well as more challenging scenarios, such as large R-group changes, scaffold hopping, formal charge changes, and charge-shifting transformations. The novel coordinate perturbation scheme and a dual-topology approach of ATM address some of the challenges of single-topology alchemical RBFE methods. Specifically, ATM eliminates the need for splitting electrostatic and Lennard-Jones interactions, atom mapping, defining ligand regions, and postcorrections for charge-changing perturbations. Thus, ATM is simpler and more broadly applicable than conventional alchemical methods, especially for scaffold-hopping and charge-changing transformations. Here, we performed well over 500 RBFE calculations for eight protein targets and found that ATM achieves accuracy comparable to that of existing state-of-the-art methods, albeit with larger statistical fluctuations. We discuss insights into the specific strengths and weaknesses of the ATM method that will inform future deployments. This study confirms that ATM can be applied as a production tool for RBFE predictions across a wide range of perturbation types within a unified, open-source framework.

Evolution and advances in endovascular mechanical thrombectomy of cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis (CVST) is a rare type of stroke and standard treatment involves anticoagulation. However, for some special CVST patients who are ineligible for anticoagulation or refractory to conservative treatment, endovascular treatment (EVT) may be an effective option. Mechanical thrombectomy (MT) is a commonly used treatment. Compared with anticoagulation treatment alone, MT may result in additional procedure-related complications, however, many studies have shown that it has a high rate of vessel recanalization and lower incidence of related complications in arterial large vessel occlusion stroke. In addition, the applicability of MT in children, patients with deep cerebral thrombosis, and patients with bleeding before treatment has been reported. MT combined with intravascular thrombolysis (IVT) and other multimodal therapeutic strategies, also has a good curative effect, and further research is needed to compare and optimize different treatment strategies. Owing to the low incidence of CVST, randomized controlled clinical trials with a large sample size to explore the safety and effectiveness of MT are scarce. In addition, devices specifically designed for cerebral venous sinus and effective endovascular therapies are currently not well-established. This article summarizes different endovascular instruments and multimodal therapies for cerebral venous thrombosis. We also discuss the limitations, prospects, prognostic factors, and applications in special cases of interventional thrombectomy.

Inflammation index in failure of delay functional independence after successful recanalization.

BACKGROUND: Failure of delayed neurological improvement (fDNI) following successful recanalization is a prevalent clinical phenomenon in patients who have experienced acute ischemic stroke (AIS). An investigation into the potential link between markers of systemic inflammation such as platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index known as SII, and the occurrence of fDNI in patients received successful reperfusion was conducted. METHODS: The study included patients diagnosed with AIS who underwent thrombectomy and experienced fDNI, as observed in a prospective study conducted from January 2017 to April 2020. In order to identify predictors of fDNI, we performed multivariable logistic regression and receiver operating characteristic (ROC) curve. RESULTS: Eighty-four patients (23.86%) without early neurological improvement (ENI) experienced DNI, and 268 (76.14%) patients did not show DNI. After adjustment for potential confounders, NLR (adjust OR, 2.131; 95%CI, 1.066-4.259; p = 0.032) and SII (adjust OR, 1.065; 95%CI, 1.001-1.132, p = 0.045) exhibited independent reationship with fDNI independently in multivariate analysis. The areas under AUC of multivariable NLR and SII mode were 0.862 and 0.861, respectively. CONCLUSIONS: The immune-inflammatory biomarkers, including NLR and SII, exhibited associations with DNI in patients without ENI. Further investigations are warranted to elucidate the underlying mechanisms.

Taming multiple binding poses in alchemical binding free energy prediction: the ß-cyclodextrin host-guest SAMPL9 blinded challenge.

We apply the Alchemical Transfer Method (ATM) and a bespoke fixed partial charge force field to the SAMPL9 bCD host-guest binding free energy prediction challenge that comprises a combination of complexes formed between five phenothiazine guests and two cyclodextrin hosts. Multiple chemical forms, competing binding poses, and computational modeling challenges pose significant obstacles to obtaining reliable computational predictions for these systems. The phenothiazine guests exist in solution as racemic mixtures of enantiomers related by nitrogen inversions that bind the hosts in various binding poses, each requiring an individual free energy analysis. Due to the large size of the guests and the conformational reorganization of the hosts, which prevent a direct absolute binding free energy route, binding free energies are obtained by a series of absolute and relative binding alchemical steps for each chemical species in each binding pose. Metadynamics-accelerated conformational sampling was found to be necessary to address the poor convergence of some numerical estimates affected by conformational trapping. Despite these challenges, our blinded predictions quantitatively reproduced the experimental affinities for the ß-cyclodextrin host and, to a lesser extent, those with a methylated derivative. The work illustrates the challenges of obtaining reliable free energy data in in silico drug design for even seemingly simple systems and introduces some of the technologies available to tackle them.

Evaluation of peripapillary retinal nerve fiber layer thickness in intracranial atherosclerotic stenosis.

PURPOSE: To evaluate the peripapillary retinal nerve fiber layer thickness (pRNFL) in patients with intracranial atherosclerotic stenosis (ICAS). METHODS: A cross-sectional study was performed in a general hospital. The intracranial atherosclerotic stenosis was evaluated by digital subtraction angiography (DSA), computed tomography angiography (CTA) or magnetic resonance angiography (MRA). High-definition optical coherence tomography (HD-OCT) was used to evaluate the peripapillary retinal nerve fiber layer thickness. RESULTS: A total of 102 patients, including 59(57.8%) patients with ICAS and 43(42.2%) patients without ICAS, were finally analysed in the study. The peripapillary retinal nerve fiber layer thickness (pRNFL) was reduced significantly in the average, the superior and the inferior quadrants of the ipsilateral eyes and in the superior quadrant of the contralateral eyes in patients with ICAS compared with patients without ICAS. After multivariate analysis, only the superior pRNFL thickness in the ipsilateral eyes was significantly associated with ICAS (OR,0.968; 95% CI,0.946-0.991; p = 0.006). The area under receiver operator curve was 0.679 (95% CI,0.576-0.782) for it to identify the presence of ICAS. The cut-off value of the superior pRNFL was 109.5 µm, and the sensitivity and specificity were 50.8% and 83.7%, respectively. CONCLUSION: The superior pRNFL in the ipsilateral eye was significantly associated with ICAS in this study. Larger studies are needed to explore the relation between pRNFL and ICAS further.

Efficacy and Safety of Recanalization Therapy for Acute Ischemic Stroke With Large Vessel Occlusion: A Systematic Review.

BACKGROUND AND PURPOSE: The optimal recanalization strategy for acute ischemic stroke with large vessel occlusion continues to be an area of active interest. Network meta-analysis can provide insight when direct comparative evidence is lacking. METHODS: A systematic review of the literature using PubMed, Embase, the Cochrane Central Register of Controlled Trials, and SinoMed was performed, and a search was conducted for clinical trials on ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and StrokeCenter.org. Four independent reviewers conducted the study selection, data abstraction, and quality assessments. RESULTS: The literature review identified 17 trials including 3236 patients and 8 ongoing clinical trials. Sample sizes ranged from 7 to 656 participants. Intravenous thrombolysis (IVT) was the most common intervention, followed by IVT plus mechanical thrombectomy (MT), IVT plus intraarterial thrombolysis, intraarterial thrombolysis alone, and MT alone. In the pooled network meta-analysis, IVT+MT was associated with a higher rate of independent functioning. In contrast, IVT was ranked as the most ineffective treatment strategy with respect to neurological functions, while direct MT was ranked as the least safe intervention with respect to all-cause mortality. Also, irrespective of assessment tools, endovascular treatment plus IVT led to higher successful recanalization rate than thrombolysis alone. CONCLUSIONS: Compared with other recanalization treatments, IVT+MT seems to be the most effective strategy, without increasing detrimental effects, for thrombolysis-eligible patients with large vessel occlusion-acute ischemic stroke. To improve the current evidentiary basis for recanalization treatment, future trials and real-world studies are warranted and should use unified definitions of symptomatic intracranial hemorrhage and recanalization.

Glycosylated Hemoglobin A1c Predicts Intracerebral Hemorrhage with Acute Ischemic Stroke Post-Mechanical Thrombectomy.

BACKGROUND: Intracerebral hemorrhage, including symptomatic intracerebral hemorrhage, is a serious post-mechanical thrombectomy complication in patients with acute ischemic stroke. We aimed to determine whether glycosylated hemoglobin A1c parameters could predict intracerebral hemorrhage in this patient population. METHODS: We enrolled patients with acute occlusion of the internal carotid artery or proximal middle cerebral artery and who had undergone mechanical thrombectomy. According to the glycosylated hemoglobin A1c level (%) assessed during the hospital stay, the patients were divided into two groups: > 6.5% and ≤ 6.5%. Intracerebral hemorrhage was evaluated and classified based on cranial computed tomography scans obtained within 24-48 h or when neurological conditions worsened. We assessed the outcome at the end of 90 days using the modified Rankin Scale scores. RESULTS: Among 202 patients, 86 (42.6%) suffered intracerebral hemorrhage, while 25 (12.4%) had symptomatic intracerebral hemorrhage; 35.6% of the patients had a favorable outcome (modified Rankin Scale scores 0-2). Multivariable analysis demonstrated an association of glycosylated hemoglobin A1c > 6.5% with intracerebral hemorrhage. Furthermore, glycosylated hemoglobin A1c > 6.5% was independently associated with symptomatic intracerebral hemorrhage (OR, 2.136; 95% CI, 1.279-3.567; P = 0.004). In addition, glycosylated hemoglobin A1c > 6.5% was significantly associated with increased mortality (OR, 1.511; 95% CI, 1.042-2.191; P = 0.029) and negatively associated with favorable outcome (OR, 0.480; 95% CI, 0.296-0.781; P = 0.003) at 90 days. CONCLUSIONS: Glycosylated hemoglobin A1c is an independent predictor of intracerebral hemorrhage (specifically, symptomatic intracerebral hemorrhage) in patients with acute ischemic stroke treated with mechanical thrombectomy. Further studies are needed to validate these findings.

Low-Dose Tirofiban Treatment Improves Neurological Deterioration Outcome After Intravenous Thrombolysis.

Background and Purpose- Early use of antiplatelet drugs within 24 hours after intravenous thrombolysis (IVT) has always been a confusing clinical problem. The purpose of this study was to assess the safety and efficacy of early low-dose tirofiban treatment in patients with early neurological deterioration (END) within the first 24 hours after IVT. Methods- This was a retrospective analysis of prospectively collected data of 1764 consecutive patients with acute ischemic stroke treated with IVT between January 2017 and September 2018. Patients with early neurological deterioration within the first 24 hours after IVT were treated with or without tirofiban. The safety outcomes included symptomatic intracranial hemorrhage, any ICH, severe systemic bleeding, and mortality. Efficacy outcomes included excellent (modified Rankin scale scores 0-1) and favorable (modified Rankin scale scores 0-2) 3-month functional outcomes. Results- Early neurological deterioration occurred in 278 (15.8%) patients. Of the 187 eligible patients, 121 (64.7%) were treated with tirofiban within the first 24 hours after IVT. Adjusted multivariate analysis showed that early tirofiban use was not associated with symptomatic intracranial hemorrhage (adjusted odds ratio [aOR], 1.05; 95% CI, 0.088-11.02; P=1.000), ICH (aOR, 1.13; 95% CI, 0.45-4.25; P=0.512), and mortality (aOR, 0.77; 95% CI, 0.19-2.27; P=0.875) but was significantly associated with excellent (aOR, 2.24; 95% CI, 1.16-3.94; P=0.027) and favorable (aOR, 2.31; 95% CI, 1.48-3.99; P=0.011) functional outcomes. Subgroup analyses suggested that early tirofiban-use efficacy is time dependent, being more effective in patients receiving tirofiban treatment earlier. Conclusions- Low-dose tirofiban use in patients with early neurological deterioration within the first 24 hours after IVT did not increase the risk of symptomatic intracranial hemorrhage, ICH, and mortality, it seems associated with neurological improvement at 3 months. Future randomized clinical trials will be needed to validate these results.

Toward Atomistic Modeling of Irreversible Covalent Inhibitor Binding Kinetics.

Covalent inhibitors have emerged as an important drug class in recent years, largely due to their many unique advantages as compared to noncovalent inhibitors, including longer duration of action, lower prolonged systemic exposure, higher potency, and selectivity. However, the potential off-target toxicity of covalent inhibitors, particularly of irreversible covalent inhibitors, represents a great challenge in covalent drug development. Therefore, accurate calculation of protein covalent inhibitor reaction kinetics to guide the design of selective inhibitors would greatly benefit covalent drug discovery efforts. In the present paper, we present a computational method to calculate the relative reaction kinetics between congeneric irreversible covalent inhibitors and their protein receptors. The method combines density functional theory calculations of the transition state barrier height of the rate-limiting step for reaction between the warhead of the inhibitor and a single protein residue, and molecular-mechanics-based free energy calculations to account for the interactions between the ligand in the transition state and the protein environment. The method was tested on four pharmaceutically interesting irreversible covalent binding systems involving 28 ligands; the mean unsigned error (MUE) of the relative reaction rate for all pairs of ligands between the predictions and experimental results for these tested systems is 0.79 log unit. This is to our knowledge the first time where the reaction kinetics of protein irreversible covalent inhibition have been directly calculated with physics-based free energy calculation methods and transition state theory. We anticipate the outstanding accuracy demonstrated here across a broad range of target classes will have a strong impact on the design of selective covalent inhibitors.

Angioplasty and/or stenting after thrombectomy in patients with underlying intracranial atherosclerotic stenosis.

PURPOSE: To investigate the imaging and clinical outcomes of emergent angioplasty and/or stenting or neither in patients of emergent large-vessel occlusion (ELVO) with underlying severe intracranial atherosclerotic stenosis (ICAS). METHODS: In this multicenter prospective cohort study, we included patients of ELVO with underlying ICAS. Patients received emergent angioplasty and/or stenting or neither after mechanical thrombectomy at the interventionists' discretion. The primary outcome was recanalization rate at 24 h, which was defined as a modified arterial occlusive lesion score of 2 or 3. RESULTS: A total of 113 consecutive patients with underlying ICAS > 70% in anterior cerebral circulation were enrolled in this study. Of these, 81 (71.7%) received emergent angioplasty and/or stenting after thrombectomy. Patients in the emergent angioplasty and/or stenting group were significantly more likely to have recanalization at 24 h (adjusted OR [aOR], 3.782; 95% confidence interval [CI], 1.821-9.125; P = 0.02) and less likely to have early neurologic deterioration (aOR, 0.299; 95% CI, 0.110-0.821; P = 0.01). However, emergent angioplasty and/or stenting was not significantly associated with symptomatic intracranial hemorrhage (aOR, 0.710; 95% CI, 0.199-2.622; P = 0.67), asymptomatic intracranial hemorrhage (aOR, 1.325; 95% CI, 0.567-3.031; P = 0.81), death at 90 days (aOR, 0.581; 95% CI, 0.186-2.314; P = 0.41), and functional independence at 90 days (aOR, 1.752; 95% CI, 0.774-3.257; P = 0.16), compared with patients that received neither. CONCLUSION: Emergent angioplasty and/or stenting is possible in patients of ELVO with ICAS and may reduce the risk of reocclusion and early neurologic deterioration with no increased risk of intracranial hemorrhage and death than those received neither.

Obstructive Sleep Apnea before Ischemic Stroke: Clinical Relevance to Infarction Volume and Neurological Recovery.

BACKGROUND: Obstructive sleep apnea (OSA) is a probable risk factor with speculative roles in the induction or aggravation of acute ischemic stroke (AIS). METHODS: The association between OSA and AIS severity was retrospectively analyzed using clinical data of first-onset AIS patients, admitted to our hospital between January 2013 and September 2016. Eligible patients were categorized based on the presence of OSA prior to stroke. Stroke severity and functional outcomes were evaluated using the National Institute of Health Stroke Severity Scale (NIHSS) and the modified Rankin scale (mRS), respectively. RESULTS: No significant differences were observed among OSA and non-OSA groups for infarction volume, NIHSS at admission and discharge, or mRS at discharge and at the 3-month follow-up (all P > .05). OSA prior to stroke negatively correlated with infarction volume (P = .008), NIHSS at discharge (P = .006), and the 3-month mRS (P = .015). In addition to OSA, it was also found that infarction volume significantly correlated with large artery occlusion (LAO), anterior circulation involvement, neutrophil count, and fibrinogen level; NIHSS at discharge significantly correlated with LAO, transient ischemia attack (TIA), neutrophil count, and thrombolysis; and the 3-month mRS significantly correlated with LAO, TIA, age, neutrophil count, and thrombolysis. CONCLUSIONS: OSA before AIS does not increase the severity of stroke. The negative association between OSA and infarction volume, stroke severity, and clinical outcomes suggests an endogenous neuroprotective effect.

Asymptomatic Intracerebral Hemorrhage May Worsen Clinical Outcomes in Acute Ischemic Stroke Patients Undergoing Thrombectomy.

BACKGROUND: Asymptomatic intracerebral hemorrhage (AICH) is a common phenomenon in patients with acute ischemic stroke (AIS) who were treated with endovascular thrombectomy (ET). This study aimed to evaluate the clinical effects of AICH and its risk factors in this patient population. METHODS: This observational study was based on a prospective registry study. AIS patients with large-vessel occlusion in the anterior circulation and treated with ET were recruited. During thrombectomy procedures, intra-arterial infusion of thrombolytics or antiplatelet and permanent stenting were used as remedial therapies. The primary outcome was the overall distribution of modified Rankin scale (mRS) 90 days after ET. RESULTS: This study included 102 patients (61.1 ± 12.7 years old), in whom 39 patients (38.2%) experienced AICH. At 90-day follow-up, the median mRS was 2 (interquartile range [IQR] 0-3) for patients without AICH and 4 (IQR 2-6) for those with AICH (adjusted P = .005). Fourteen patients with AICH and 7 patients without AICH died, which was significantly different (35.9% versus 11.1%, adjusted P = .015). Thirty-nine patients (61.9%) without AICH and 14 patients (35.9%) with AICH achieved functional independence at 3-month follow-up (adjusted P = .117). The length of intensive care unit staying was 5 days (IQR 2-10) in patients without AICH and 8 days (IQR 3-19) in those with AICH (adjusted P = .840). In multivariate analysis, lower Alberta Stroke Program Early CT Score (ASPECTS) (adjusted P = .003) and adjunctively intra-arterial thrombolysis (adjusted P = .016) were independently associated with AICH. CONCLUSIONS: In AIS patients treated with ET AICH appears to be associated with worse functional outcomes and high mortality. Lower ASPECTS and adjectively intra-arterial thrombolysis were independent risk factors of AICH.

Outcome of endovascular treatment for acute basilar artery occlusion in the modern era: a single institution experience.

PURPOSE: The beneficial effect of endovascular treatment (EVT) for patients with acute basilar artery occlusion (ABAO) remains uncertain. The purpose of the present study was to evaluate clinical outcome of EVT for patients with ABAO and analyze prognostic factors of good outcome. METHODS: From our prospectively established database, we reviewed all patients with ABAO receiving EVT during January 2014 to December 2016. Baseline characteristics and outcomes were evaluated. Favorable functional outcome was defined as modified Rankin Scale score of 0 to 3 assessed at 3-month follow-up. The association between clinical and procedural characteristics and functional outcome was assessed. RESULTS: Of the 68 patients included, 50 patients (73.5%) received mechanical thrombectomy with stent retriever device. Successful reperfusion (thrombolysis in cerebral infarction grades 2b-3) was achieved in 61 patients (89.7%). Overall favorable functional outcome was reached by 31 patients (45.6%). In univariate analysis, Glasgow Coma Scale sum score, baseline National Institutes of Health stroke scale score (NIHSS), and baseline glycemia level were identified predicting good clinical outcome. Multivariate analysis showed that lower NIHSS was the only independent risk factor of favorable functional outcome (OR 0.832; 95% CI, 0.715-0.968; p = 0.018). No difference of favorable outcomes was observed between the subgroups of time to EVT < 6 h and ≽ 6 h. CONCLUSIONS: Data in the present study suggests that EVT for ABAO patients should be reasonable within 24 h of symptom onset. The most important factor determining clinical outcome is initial stroke severity.