Microsnare retrieval as a bail-out technique of Detached Woven EndoBridge device: Illustrative series.

BACKGROUND: The Woven EndoBridge (WEB) device (MicroVention, Tustin, CA, USA) has an excellent safety profile. While major complications such as device malposition and migration are rare, they can have serious consequences if not addressed promptly. Our case series describes the safety and efficacy of Amplatz goose neck microsnare device (Medtronic in Irvine, CA, USA) in endovascular retrieval of a detached WEB device. METHODS: We retrospectively reviewed six consecutive patients who underwent endovascular WEB retrieval using Amplatz microsnare device between March 2012 and December 2022. RESULTS: All six WEB devices were successfully retrieved either directly from the aneurysm sac due to device malpositioning or from a distal branch following device migration. None of the patients experienced intra-operative aneurysm perforation, arterial dissection, or vasospasm attributable to the process of WEB extraction. Five out of six patients (83.3%) had a good functional outcome (mRS 0-1) upon discharge from the hospital and at 24 months. CONCLUSION: Our experience suggests that detached WEB devices can be safely retrieved using an Amplatz microsnare. Apart from addressing device migration, direct removal of an undersized or malpositioned WEB from the aneurysm sac appears to be a safe option that can be considered when all other rescue techniques have been exhausted.

Safety and efficacy of adjunctive intra-arterial antithrombotic therapy during endovascular thrombectomy for acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Half of patients who achieve successful recanalization following endovascular thrombectomy (EVT) for acute ischemic stroke experience poor functional outcome. We aim to investigate whether the use of adjunctive intra-arterial antithrombotic therapy (AAT) during EVT is safe and efficacious compared with standard therapy (ST) of EVT with or without prior intravenous thrombolysis. METHODS: Electronic databases were searched (PubMed/MEDLINE, Embase, Cochrane Library) from 2010 until October 2023. Data were pooled using a random-effects model and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias was assessed using ROBINS-I and ROB-2. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes were successful recanalization (modified Thrombolysis In Cerebral Infarction (TICI) 2b-3), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. RESULTS: 41 randomized and non-randomized studies met the eligibility criteria. Overall, 15 316 patients were included; 3296 patients were treated with AAT during EVT and 12 020 were treated with ST alone. Compared with ST, patients treated with AAT demonstrated higher odds of functional independence (46.5% AAT vs 42.6% ST; OR 1.22, 95% CI 1.07 to 1.40, P=0.004, I2=48%) and a lower likelihood of 90-day mortality (OR 0.71, 95% CI 0.61 to 0.83, P<0.0001, I2=20%). The rates of sICH (OR 1.00, 95% CI 0.82 to 1.22,P=0.97, I2=13%) and successful recanalization (OR 1.09, 95% CI 0.84 to 1.42, P=0.52, I2=76%) were not significantly different. CONCLUSION: The use of AAT during EVT may improve functional outcomes and reduce mortality rates compared with ST alone, without an increased risk of sICH. These findings should be interpreted with caution pending the results from ongoing phase III trials to establish the efficacy and safety of AAT during EVT.

Lateral Compression Manipulation: A Simple Approach for Sizing Taller-Than-Wide Intracranial Aneurysms with the Woven EndoBridge Device.

BACKGROUND AND PURPOSE: The Woven EndoBridge (WEB) system has established itself as a safe and effective option for managing wide-neck bifurcation aneurysms. Addressing aneurysms with a greater height than width using conventional WEB-sizing methods has proved ineffective due to the inherent configuration of the devices. To overcome this limitation, we propose an intuitive approach that involves swapping the width and height dimensions of the aneurysm to determine the appropriate WEB size. MATERIALS AND METHODS: A retrospective analysis was conducted on patients undergoing WEB embolization at a single neuroscience center from March 2013 to February 2023. RESULTS: Twenty-five eligible aneurysms were identified, with the height dimension exceeding the width by an average of 2.33 mm (ranging from 1.4 to 4.5 mm). Of these, 20 cases adhered to the recommended sizing technique, resulting in a 100% success rate of adequate occlusion (14/20 complete occlusion, 6/20 proximal recess filling). In contrast, the outcomes for the remaining 5 cases that did not follow the proposed sizing method were less favorable (P < .05). Among these, 4 cases treated with undersized WEBs showed neck remnants during follow-up, and 1 patient who received an oversized WEB required device replacement during the same procedure. CONCLUSIONS: The simple sizing method we proposed for treating taller-than-wide aneurysms has demonstrated promising results, allowing the WEB system to address twice the original size range of treatable aneurysms. Further research with a larger sample size is recommended.

Effect of proximal blood flow arrest during endovascular thrombectomy (ProFATE): Study protocol for a multicentre randomised controlled trial.

BACKGROUND: Observational studies have demonstrated improved outcomes with the adjunctive use of balloon guide catheters (BGC) during endovascular thrombectomy (EVT) for anterior circulation acute ischaemic stroke (AIS). However, the lack of high-level evidence and global practice heterogeneity justifies a randomised controlled trial (RCT) to investigate the effect of transient proximal blood flow arrest on the procedural and clinical outcomes of patients with AIS following EVT. HYPOTHESIS: Proximal blood flow arrest in the cervical internal carotid artery during EVT for proximal large vessel occlusion is superior to no flow arrest in achieving complete vessel recanalisation. METHODS: ProFATE is an investigator-initiated, pragmatic, multicentre RCT with blinding of participants and outcome assessment. An estimated 124 participants with an anterior circulation AIS due to large vessel occlusion, an NIHSS of ⩾2, ASPECTS ⩾ 5 and eligible for EVT using a first-line combined technique (contact aspiration and stent retriever) or contact aspiration only will be randomised (1:1) to receive BGC balloon inflation or no inflation during EVT. OUTCOMES: The primary outcome is the proportion of patients achieving near-complete/complete vessel recanalisation (eTICI 2c-3) at the end of the EVT procedure. Secondary outcomes include the functional outcome (modified Rankin Scale at 90 days), new or distal vascular territory clot embolisation rate, near-complete/complete recanalisation after the first pass, symptomatic intracranial haemorrhage, procedure-related complications and death at 90 days. DISCUSSION: This is the first RCT to investigate the effect of proximal blood flow arrest during EVT using a BGC on the procedural and clinical outcomes of patients with AIS due to large vessel occlusion.

Incidence and predictors of poor functional outcome despite complete recanalisation following endovascular thrombectomy for acute ischaemic stroke.

BACKGROUND: Numerous ischaemic stroke patients experience poor functional outcome despite successful recanalisation following endovascular thrombectomy (EVT). We aimed to identify the incidence and predictors of futile complete recanalisation (FCR) in a national stroke registry. METHODS: Patients who achieved complete recanalisation (mTICI 3) following EVT, between October 2015 and March 2020, were included from a United Kingdom national stroke registry. Modified Rankin Scale of 4-6 at discharge was defined as a 'poor/futile outcome'. Backward stepwise multivariable logistic regression analysis was performed with FCR as the dependent variable, incorporating all baseline characteristics, procedural time metrics and post-procedural events. RESULTS: We included 2132 of 4383 patients (48.8%) with complete recanalisation post-EVT, of which 948 patients (44.4%) developed FCR. Following multivariable regression analysis adjusted for potential confounders, patients with FCR were associated with multiple baseline patient, imaging and procedural factors: age (p=0.0001), admission NIHSS scores (p=0.0001), pre-stroke disability (p=0.007), onset-to-puncture (p=0.0001) and procedural times (p=0.0001), presence of diabetes (p=0.005), and use of general anaesthesia (p=0.0001). Although not predictive of outcome, post-procedural events including development of any intracranial haemorrhage (ICH) (p=0.0001), symptomatic ICH (sICH) (p=0.0001) and early neurological deterioration (END) (p=0.007) were associated with FCR. CONCLUSION: Nearly half of patients in this national registry experienced FCR following EVT. Significant predictors of FCR included increasing age, admission NIHSS scores, pre-stroke disability, onset-to-puncture and procedural times, presence of diabetes, atrial fibrillation, and use of general anaesthesia. Post procedural development of any ICH, sICH, and END were associated with FCR.

Association between time to treatment and clinical outcomes in endovascular thrombectomy beyond 6 hours without advanced imaging selection.

BACKGROUND: The effectiveness and safety of endovascular thrombectomy (EVT) in the late window (6-24 hours) for acute ischemic stroke (AIS) patients selected without advanced imaging is undetermined. We aimed to assess clinical outcomes and the relationship with time-to-EVT treatment beyond 6 hours of stroke onset without advanced neuroimaging. METHODS: Patients who underwent EVT selected with non-contrast CT/CT angiography (without CT perfusion or MR imaging), between October 2015 and March 2020, were included from a national stroke registry. Functional and safety outcomes were assessed in both early (<6 hours) and late windows with time analyzed as a continuous variable. RESULTS: Among 3278 patients, 2610 (79.6%) and 668 (20.4%) patients were included in the early and late windows, respectively. In the late window, for every hour delay, there was no significant association with shift towards poorer functional outcome (modified Rankin Scale (mRS)) at discharge (adjusted common OR 0.98, 95% CI 0.94 to 1.01, p=0.27) or change in predicted functional independence (mRS ≤2) (24.5% to 23.3% from 6 to 24 hours; aOR 0.99, 95% CI0.94 to 1.04, p=0.85). In contrast, predicted functional independence was time sensitive in the early window: 5.2% reduction per-hour delay (49.4% to 23.5% from 1 to 6 hours, p=0.0001). There were similar rates of symptomatic intracranial hemorrhage (sICH) (3.4% vs 4.6%, p=0.54) and in-hospital mortality (12.9% vs 14.6%, p=0.33) in the early and late windows, respectively, without a significant association with time. CONCLUSION: In this real-world study, there was minimal change in functional disability, sICH and in-hospital mortality within and across the late window. While confirmatory randomized trials are needed, these findings suggest that EVT remains feasible and safe when performed in AIS patients selected without advanced neuroimaging between 6-24 hours from stroke onset.

Endovascular thrombectomy beyond 24 hours from ischemic stroke onset: a propensity score matched cohort study.

BACKGROUND: The safety and functional outcome of endovascular thrombectomy (EVT) in the very late (VL; >24 hours) time window from ischemic stroke onset remains undetermined. METHODS: Using data from a national stroke registry, we used propensity score matched (PSM) individual level data of patients who underwent EVT, selected with CT perfusion or non-contrast CT/CT angiography, between October 2015 and March 2020. Functional and safety outcomes were assessed in both late (6-24 hours) and VL time windows. Subgroup analysis was performed of imaging selection modality in the VL time window. RESULTS: We included 1150 patients (late window: 1046 (208 after PSM); VL window: 104 (104 after PSM)). Compared with EVT treatment initiation between 6 and 24 hours, patients treated in the VL window had similar modified Rankin Scale (mRS) scores at discharge (ordinal shift; common OR=1.08, 95% CI 0.69 to 1.47, p=0.70). No significant differences in achieving good functional outcome (mRS ≤2 at discharge; 28.8% (VL) vs 29.3% (late), OR=0.97, 95% CI 0.58 to 1.64, p=0.93), successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b-3) (p=0.77), or safety outcomes of symptomatic intracranial hemorrhage (p=0.43) and inhospital mortality (p=0.23) were demonstrated. In the VL window, there was no significant difference in functional outcome among patients selected with perfusion versus those selected without perfusion imaging (common OR=1.38, 95% CI 0.81 to 1.76, p=0.18). CONCLUSION: In this real world study, EVT beyond 24 hours from stroke onset or last known well appeared to be feasible, with comparable safety and functional outcomes to EVT initiation between 6 and 24 hours. Randomized trials assessing the efficacy of EVT in the VL window are warranted, but may only be feasible with a large international collaborative approach.

Association between anesthesia modality and clinical outcomes following endovascular stroke treatment in the extended time window.

BACKGROUND: There is a paucity of data on anesthesia-related outcomes for endovascular treatment (EVT) in the extended window (>6 hours from ischemic stroke onset). We compared functional and safety outcomes between local anesthesia (LA) without sedation, conscious sedation (CS) and general anesthesia (GA). METHODS: Patients who underwent EVT in the early (<6 hours) and extended time windows using LA, CS, or GA between October 2015 and March 2020 were included from a UK national stroke registry. Multivariable analyses were performed, adjusted for age, sex, baseline stroke severity, pre-stroke disability, EVT technique, center, procedural time and IV thrombolysis. RESULTS: A total of 4337 patients were included, 3193 in the early window (1135 LA, 446 CS, 1612 GA) and 1144 in the extended window (357 LA, 134 CS, 653 GA). Compared with GA, patients treated under LA alone had increased odds of an improved modified Rankin Scale (mRS) score at discharge (early: adjusted common (ac) OR=1.50, 95% CI 1.29 to 1.74, p=0.001; extended: acOR=1.29, 95% CI 1.01 to 1.66, p=0.043). Similar mRS scores at discharge were found in the LA and CS cohorts in the early and extended windows (p=0.21). Compared with CS, use of GA was associated with a worse mRS score at discharge in the early window (acOR=0.73, 95% CI 0.45 to 0.96, p=0.017) but not in the extended window (p=0.55). There were no significant differences in the rates of symptomatic intracranial hemorrhage or in-hospital mortality across the anesthesia modalities in the extended window. CONCLUSION: LA without sedation during EVT was associated with improved functional outcomes compared with GA, but not CS, within and beyond 6 hours from stroke onset. Prospective studies assessing anesthesia-related outcomes in the extended time window are warranted.

Perfusion Imaging for Endovascular Thrombectomy in Acute Ischemic Stroke Is Associated With Improved Functional Outcomes in the Early and Late Time Windows.

BACKGROUND: The impact on clinical outcomes of patient selection using perfusion imaging for endovascular thrombectomy (EVT) in patients with acute ischemic stroke presenting beyond 6 hours from onset remains undetermined in routine clinical practice. METHODS: Patients from a national stroke registry that underwent EVT selected with or without perfusion imaging (noncontrast computed tomography/computed tomography angiography) in the early (<6 hours) and late (6-24 hours) time windows, between October 2015 and March 2020, were compared. The primary outcome was the ordinal shift in the modified Rankin Scale score at hospital discharge. Other outcomes included functional independence (modified Rankin Scale score ≤2) and in-hospital mortality, symptomatic intracerebral hemorrhage, successful reperfusion (Thrombolysis in Cerebral Infarction score 2b-3), early neurological deterioration, futile recanalization (modified Rankin Scale score 4-6 despite successful reperfusion) and procedural time metrics. Multivariable analyses were performed, adjusted for age, sex, baseline stroke severity, prestroke disability, intravenous thrombolysis, mode of anesthesia (Model 1) and including EVT technique, balloon guide catheter, and center (Model 2). RESULTS: We included 4249 patients, 3203 in the early window (593 with perfusion versus 2610 without perfusion) and 1046 in the late window (378 with perfusion versus 668 without perfusion). Within the late window, patients with perfusion imaging had a shift towards better functional outcome at discharge compared with those without perfusion imaging (adjusted common odds ratio [OR], 1.45 [95% CI, 1.16-1.83]; P=0.001). There was no significant difference in functional independence (29.3% with perfusion versus 24.8% without; P=0.210) or in the safety outcome measures of symptomatic intracerebral hemorrhage (P=0.53) and in-hospital mortality (10.6% with perfusion versus 14.3% without; P=0.053). In the early time window, patients with perfusion imaging had significantly improved odds of functional outcome (adjusted common OR, 1.51 [95% CI, 1.28-1.78]; P=0.0001) and functional independence (41.6% versus 33.6%, adjusted OR, 1.31 [95% CI, 1.08-1.59]; P=0.006). Perfusion imaging was associated with lower odds of futile recanalization in both time windows (late: adjusted OR, 0.70 [95% CI, 0.50-0.97]; P=0.034; early: adjusted OR, 0.80 [95% CI, 0.65-0.99]; P=0.047). CONCLUSIONS: In this real-world study, acquisition of perfusion imaging for EVT was associated with improvement in functional disability in the early and late time windows compared with nonperfusion neuroimaging. These indirect comparisons should be interpreted with caution while awaiting confirmatory data from prospective randomized trials.

The Role of Non-statin Lipid-Lowering Medications in Youth with Hypercholesterolemia.

PURPOSE OF REVIEW: Lifestyle modification is additive to lipid-lowering medications in the treatment of heterozygous familial hypercholesterolemia (HeFH), which does not respond sufficiently to statin therapy. While both are also important in homozygous familial hypercholesterolemia (HoFH), additional measures such as apheresis may be needed. The purpose of this review is to identify non-statin medications to lower cholesterol that are available for children and adolescents as adjunctive therapy. RECENT FINDINGS: Ezetimibe is commonly used as second-line pharmacotherapy for treatment of HeFH and HoFH. Colesevelam, a bile acid sequestrant, may be considered for adjunct therapy. Since 2015, the PCSK9 inhibitor evolocumab has been available for adolescents, and its FDA approval has now expanded to age 10 years. The ANGPTL3 inhibitor evinacumab has been approved for children age 12 years and older. A clinical trial for lomitapide is in progress. Approvals for PCSK9 and ANGPTL3 inhibitors have expanded opportunities for children and adolescents with HeFH and HoFH to achieve lower LDL-C levels.

Local anesthesia as a distinct comparator versus conscious sedation and general anesthesia in endovascular stroke treatment: a systematic review and meta-analysis.

BACKGROUND: The optimal anesthetic modality for endovascular treatment (EVT) in acute ischemic stroke (AIS) is undetermined. Comparisons of general anesthesia (GA) with composite non-GA cohorts of conscious sedation (CS) and local anesthesia (LA) without sedation have provided conflicting results. There has been emerging interest in assessing whether LA alone may be associated with improved outcomes. We conducted a systematic review and meta-analysis to evaluate clinical and procedural outcomes comparing LA with CS and GA. METHODS: We reviewed the literature for studies reporting outcome variables in LA versus CS and LA versus GA comparisons. The primary outcome was 90 day good functional outcome (modified Rankin Scale (mRS) score of ≤2). Secondary outcomes included mortality, symptomatic intracerebral hemorrhage, excellent functional outcome (mRS score ≤1), successful reperfusion (Thrombolysis in Cerebral Infarction (TICI) >2b), procedural time metrics, and procedural complications. Random effects meta-analysis was performed on unadjusted and adjusted data. RESULTS: Eight non-randomized studies of 7797 patients (2797 LA, 2218 CS, and 2782 GA) were identified. In the LA versus GA comparison, no statistically significant differences were found in unadjusted analyses for 90 day good functional outcome or mortality (OR=1.22, 95% CI 0.84 to 1.76, p=0.3 and OR=0.83, 95% CI 0.64 to 1.07, p=0.15, respectively) or in the LA versus CS comparison (OR=1.14, 95% CI 0.76 to 1.71, p=0.53 and OR=0.88, 95% CI 0.62 to 1.24, p=0.47, respectively). There was a tendency towards achieving excellent functional outcome (mRS ≤1) in the LA group versus the GA group (OR=1.44, 95% CI 1.00 to 2.08, p=0.05, I2=70%). Analysis of adjusted data demonstrated a tendency towards higher odds of death at 90 days in the GA versus the LA group (OR=1.24, 95% CI 1.00 to 1.54, p=0.05, I2=0%). CONCLUSION: LA without sedation was not significantly superior to CS or GA in improving outcomes when performing EVT for AIS. However, the quality of the included studies impaired interpretation, and inclusion of an LA arm in future well designed multicenter, randomized controlled trials is warranted.

Implantation of Large Diameter (5.5-6 mm) Derivo Embolization Devices for the Treatment of Cerebral Aneurysms.

BACKGROUND: The efficacy of flow diverters is dependent upon robust wall apposition in the parent artery. Usage in large caliber cerebral vessels has therefore been limited as few implants with diameters > 5 mm exist. We present our initial experience in treating cerebral aneurysms using the 5.5 mm and 6 mm diameter implants of the Derivo embolization device (DED). METHODS: Our prospectively maintained institutional database was reviewed to identify patients in whom a > 5 mm DED was implanted between November 2016 and February 2021. The primary efficacy outcome was complete or near-complete aneurysm occlusion at 6 months (O'Kelly-Marotta, OKM, C-D, adapted for magnetic resonance angiography). Safety outcomes included 30-day major morbidity defined as modified Rankin Score (mRS) 3-5, mortality, serious adverse events and procedural complications. RESULTS: A total of 21 large diameter DEDs were deployed in 18 patients (age 59.5 ± 14.1 years), harboring 19 unruptured aneurysms. Of the aneurysms 14 (73.7%) were saccular in morphology (sac diameter 10.9 ± 5.5 mm, neck diameter 6.8 ± 3.1 mm), 3 (15.8%) aneurysms were dissecting, 1 (5.3%) iatrogenic pseudoaneurysm and 1 (5.3%) fusiform. Aneurysm locations were: ICA (internal carotid artery) (n = 17); (7 cavernous, 4 paraophthalmic, 2 paraclinoid, 1 petrous, 2 communicating, 1 cervical); vertebrobasilar (n = 2). Adjunct stenting to optimize proximal wall apposition was undertaken in 5 (27.8%) patients. At 6 months 75% of patients followed-up met the primary efficacy endpoint (OKM C-D). There were no serious adverse events, 30-day major morbidity (mRS 3-5) or mortality. CONCLUSION: Implantation of large diameter (5.5 mm and 6 mm) DEDs into capacious cerebral vessels to treat a range of complex aneurysms is safe and technically feasible but may require adjunct stenting to optimize proximal wall apposition. Short-term efficacy of this device subset is comparable to previous DED and other flow diverter studies. Long-term follow-up and comparative studies are required for further assessment.

Isolated clival subdural haemorrhage from a dolicoectactic vertebrobasilar aneurysm: Case report and overview of endovascular treatment strategies.

Posterior fossa aneurysms presenting with isolated subdural haemorrhage (SDH) have scarcely been described with no cases attributed to a vertebrobasilar (VB) location. Non-saccular VB aneurysms are a distinct sub-group and in this report we also discuss the pathophysiology and treatment options for these difficult-to-manage lesions. We present a case of a 49 year-old man who presented with a 7-day history of severe headaches who was found to have an isolated acute clival SDH. Vascular imaging revealed a VB dolicoectatic segment with superimposed fusiform dilatations that contacted the dura adjacent to the SDH. A staged treatment was performed with initial parental vessel occlusion of the ruptured vertebral artery segment and subsequent insertion of a braided stent (LEO) with flow diverting properties into the progressively dilating basilar artery. A third procedure was performed to occlude a recurrent pouch at the lower basilar dilatation. Complete angiographic occlusion was achieved and the patient is under continued surveillance. To our knowledge, this is the first case of a ruptured non-saccular VB aneurysm presenting with radiologically isolated clival SDH. Clinical history will often inform the need for vascular imaging in such atypical presentations. Managing these lesions remains an endovascular challenge and requires a specialist multi-disciplinary approach.

Left Atrial Enlargement on Non-Gated CT Is Associated with Large Vessel Occlusion in Acute Ischaemic Stroke.

BACKGROUND: Recent reports have suggested that atrial fibrillation (AF) is more prevalent in the large vessel occlusion (LVO) subgroup of acute ischaemic stroke patients. Given the association between left atrial enlargement (LAE) and AF, we sought to evaluate the feasibility of assessing LAE on non-gated CT and its association with LVO in the hyperacute stroke setting. METHODS: We analysed our prospectively collected database that included all stroke patients referred for consideration of endovascular treatment between April 14, 2020, and May 21, 2020. During this period, a CT chest was included in our regional stroke protocol to aid triage of patients suspected for COVID-19 from which cardiac measurements were obtained. Patients were dichotomized into LVO and no-LVO groups, and LA measurements were trichotomized into normal, borderline, and enlarged. Univariate analyses were performed between groups. RESULTS: Of the included 38 patients, 21 were categorized as LVO and 17 as no LVO. There was a statistically significant association between LAE and LVO (p = 0.028). No significant difference was demonstrated between groups for the baseline AF and other clinical characteristics, except for baseline NIHSS (p = 0.0005). There was excellent inter- and intra-rater reliability (ICC = 0.969) for LA measurements. CONCLUSION: Our study provides preliminary data to suggest LAE is more prevalent in the LVO stroke subgroup at presentation and can be reliably assessed on non-gated CT in the hyperacute setting. These findings have potential implications for stratifying secondary management and may prompt a more rigorous pursuit of occult AF or other cardiac causes of stroke.

Direct mechanical thrombectomy without intravenous thrombolysis versus bridging therapy for acute ischemic stroke: A meta-analysis of randomized controlled trials.

BACKGROUND: Direct mechanical thrombectomy may result in similar outcomes compared to a bridging approach with intravenous thrombolysis (IVT + MT) in acute ischemic stroke. Recent randomized controlled trials have varied in their design and noninferiority margin. AIM: We sought to meta-analyze accumulated trial data to assess the difference and non-inferiority in clinical and procedural outcomes between direct mechanical thrombectomy and bridging therapy. SUMMARY OF REVIEW: We conducted a systematic review of electronic databases following the preferred reporting items for systematic reviews and meta-analyses guidelines. Random effects meta-analyses were conducted for the pooled data. The primary outcome was good functional outcome at 90 days (modified Rankin scale (mRS) ≤ 2). Secondary outcomes included excellent functional outcome (mRS ≤ 1), mortality, any intracranial hemorrhage, symptomatic intracranial hemorrhage, successful reperfusion (thrombolysis in cerebral infarction ≥ 2 b), and procedure-related complications. Four randomized controlled trials comprising 1633 patients (817 direct mechanical thrombectomy, 816 bridging therapy) were included. There were no statistical differences for the 90-day good functional outcome (OR = 1.02, 95% CI 0.84-1.25, p = 0.54, I2 = 0%), and the absolute risk difference was 1% (95% CI: -4% to 5%). The lower 95% CI falls within the strictest noninferiority margin of -10% among included randomized control trials. Direct mechanical thrombectomy reduced the odds of successful reperfusion (OR = 0.76, 95% CI: 0.60-0.97, p = 0.03, I2 = 0%) and any intracranial hemorrhage (OR = 0.65, 95% CI: 0.49-0.86, p = 0.003, I2 = 38%). There was no difference in the remaining secondary outcomes. The risk of bias for all studies was low. CONCLUSION: The combined trial data assessing direct mechanical thrombectomy versus bridging therapy showed no difference in improving good functional outcome. The wide noninferiority thresholds set by individual trials are in contrast with the clinical consensus on minimally important differences. However, our pooled analysis indicates noninferiority of direct mechanical thrombectomy with a 4% margin of confidence. The application of these findings is limited to patients presenting directly to mechanical thrombectomy-capable centers and real-world workflow times may differ against those achieved in a trial setting.

Flow-related posterior cerebral artery aneurysms with internal carotid artery occlusions: An institutional series.

BACKGROUND: Aneurysm formation after internal carotid artery (ICA) occlusion has been described in animal models and human case series with alteration of cerebral blood flow dynamics considered an aetiological risk factor. Such de novo aneurysms have seldom been described in the posterior cerebral artery (PCA) with the majority observed in the anterior circulation collateral pathways. METHODS: We retrospectively reviewed our institutional database of posterior circulation aneurysms in patients with iatrogenic, atherosclerotic or congenital ICA occlusions. A comprehensive review of the online literature using the PubMed and Medline databases was performed to identify previous cases of PCA aneurysms that were considered 'flow-related'. RESULTS: We present five patients with symptomatic or ruptured PCA aneurysms with ICA occlusions. Age at presentation ranged from 21-58 and aneurysm size from 3-12 mm. All cases had angiographic evidence of posterior-anterior flow via the ipsilateral posterior communicating artery (PComA). The clinical presentation, diagnostic imaging and management strategies are further discussed. A literature review identified only two previous reported cases. CONCLUSION: To our knowledge this is the first single centre series of posterior circulation aneurysms in patients with ICA occlusions that are considered to be 'flow-related.' The natural history of these rare lesions is unclear and the best management and surveillance strategy requires a patient-tailored approach by an experienced neurovascular team.

Sleep and Circadian Regulation of Cortisol: A Short Review.

The central circadian pacemaker (CCP) located in the suprachiasmatic nucleus (SCN) of the hypothalamus drives the 24-hour pattern in cortisol, which functions as the main central synchronizing signal that coordinates peripheral clocks in organs that control whole body metabolism. A superimposed pulsatile pattern of cortisol allows rapid responses that fine tune the body's reaction to changes in the environment. In addition to coordinating metabolic processes to predictable environmental events, cortisol is the main catabolic signal which acts with testosterone, the quintessential male anabolic hormone, to maintain catabolic-anabolic homeostasis in men. Sleep restriction, when sufficiently substantial, increases late afternoon/early evening cortisol, but does not alter 24-hour cortisol; whereas even maximal acute circadian misalignment only slightly delays the cortisol rhythm. Prolonged circadian misalignment decreases overall cortisol exposure. The implications of these regulatory changes on health and disease requires further evaluation.