Brinjikji, Waleed

ImportancePrevious randomized clinical trials (RCTs) have supported the use of endovascular therapy (EVT) in late-window acute ischemic stroke (AIS; 6-24 hours). However, little is known about the use of EVT in very late-window AIS (>24 hours).ObjectiveTo examine outcomes following EVT for very late-window AIS.Data SourcesA systematic review of the English language literature was conducted using Web of Science, Embase, Scopus, and PubMed to search for articles published from database inception until December 13, 2022.Study SelectionThis systematic review and meta-analysis included published studies regarding very late-window AIS treated with EVT. Multiple reviewers screened studies, and an extensive manual search of the references of included articles was performed to identify any missed articles. Of the 1754 initially retrieved studies, 7 published between 2018 and 2023 were ultimately included.Data Extraction and SynthesisData were extracted independently by multiple authors and evaluated for consensus. Data were pooled using a random-effects model. This study is reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guideline, and the protocol was prospectively registered with PROSPERO.Main Outcomes and MeasuresThe primary outcome of interest was functional independence, as assessed with 90-day modified Rankin Scale (mRS) scores (0-2). Secondary outcomes included thrombolysis in cerebral infarction (TICI) scores (2b-3 or 3), symptomatic intracranial hemorrhage (sICH), 90-day mortality, early neurological improvement (ENI), and early neurological deterioration (END). Frequencies and means were pooled with the corresponding 95% CIs.ResultsThis review included 7 studies involving a total of 569 patients. The mean baseline National Institutes of Health Stroke Scale score was 13.6 (95% CI, 11.9-15.5), and the mean Alberta Stroke Program Early CT Score was 7.9 (95% CI, 7.2-8.7). The mean time from last known well and/or onset to puncture was 46.2 hours (95% CI, 32.4-65.9 hours). Frequencies for the primary and secondary outcomes were 32.0% (95% CI, 24.7%-40.2%) for functional independence (90-day mRS scores of 0-2) and 81.9% (95% CI, 78.5%-84.9%) for TICI scores of 2b to 3, 45.3% (95% CI, 36.6%-54.4%) for TICI scores of 3, 6.8% (95% CI, 4.3%-10.7%) for sICH, and 27.2% (95% CI, 22.9%-31.9%) for 90-day mortality. In addition, frequencies were 36.9% (95% CI, 26.4%-48.9%) for ENI and 14.3% (95% CI, 7.1%-26.7%) for END.Conclusions and RelevanceIn this review, EVT for very late-window AIS was associated with favorable frequencies of 90-day mRS scores of 0 to 2 and TICI scores of 2b to 3 and with low frequencies of 90-day mortality and sICH. These results suggest that EVT may be safe and associated with improved outcomes for very late-window AIS, although RCTs and prospective, comparative studies are needed to determine which patients may benefit from very late intervention.

Introduction Various clinical trials addressing large core acute ischemic stroke (AIS) are ongoing from multiple international groups. Future development of clinical guidelines depends on meta‐analyses of these trials calling for a degree of homogeneity of elements across the different studies. The aim of this common data element study was to provide an overview of the key features of pertinent large core infarct trials. Methods PubMed and ClinicalTrials.gov databases were screened for published and ongoing clinical trials assessing mechanical thrombectomy in patients with AIS with large core infarct. Nested Knowledge AutoLit living review platform was utilized to categorize primary and secondary outcomes as well as inclusion and exclusion criteria for patient selection in the clinical trials. Results The most reported data element was ASPECTS score, but with varied definitions of what compromises large core. Non‐utility‐weighted modified Rankin Score (mRS) was reported in 6/7 studies as the primary outcome, while the utility‐weighted mRS was the outcome of interest in the TESLA trial, all of them at the 3‐months mark, with only LASTE looking for mRS shift at the 6‐months mark. Secondary outcomes had more variations. Mortality is reported separately only in 4/7 trials, all at the 3‐month mark. Additionally, the TENSION trial reports the frequency of serious adverse events, including mortality, at the 1‐week and 12‐month mark. Conclusions In the published and the ongoing large core trials, there is a large degree of variability in the collected data elements. Differences in definition and timepoints renders reaching a unified standard difficult, which hinders high quality meta‐analyses and cohesive evidence‐driven synthesis.

Introduction EXCELLENT (NCT03685578; Cerenovus) is a large, prospective, international, real‐world registry of endovascular clot removal in acute ischemic stroke (AIS) with EmboTrap as the first line mechanical thrombectomy (MT) device, which included collection and analysis of the retrieved thrombus material. Methods Between September 2018 and March 2021, 1000 “all‐comer” patients were enrolled at 34 global sites (27 US, 5 EU, 1 UK, 1 Israel) and treated according to standard of care at each center (with Embrotrap as first line). The study employed blind endpoint evaluation, including a core imaging lab and an independent 90‐day mRS assessment. Retrieved clot was collected per each MT maneuver from 538 subjects across 26 sites and clot analysis was performed by independent central labs blinded to clinical data. Results mITT population included 998 subjects. Mean age was 69.9±14.18 years (range 18–102), 51.8% (517/998) subjects were female and 9.9% (97/997) had a pre‐stroke mRS 3–5. Baseline NIHSS was 15.6±6.87 (range 0–36); 10.1% (82/815) subjects had a large core (ASPECTS 0–5); 5.8% (57/990) had posterior stroke; 56.3% (523/929) underwent MT ≤ 6hrs of onset and 38.1% (380/998) received IV‐tPA prior to MT. First pass eTICI 2c‐3 was achieved in 38.3% (377/984) and final 2b‐3 in 94.5 % (930/984; median number of passes = 1) of subjects. 90‐day mRS≤2 or ≤pre‐stroke was 46.9% (429/915) and 90‐day all‐cause mortality was 19.0% (175/921). The univariate analysis of clot components showed high red blood cell and low platelet content were significant predictors of good mRS outcome (p < 0.001 and 0.009) and negative predictors of 90‐day mortality (p < 0.001 and 0.017, respectively). Conclusions This large multi‐center, all‐comer cohort reflects the population undergoing thrombectomy today in a real world‐setting. Final angiographic, clinical and thrombus composition results, along with multivariate analysis of predictors of clinical outcomes, will be presented at the time of the conference.

Symptomatic non-stenotic carotid plaques (SyNC) are an under-researched and under-recognized source of stroke. Various imaging markers of non-stenotic carotid plaques that are associated with stroke risk have been identified, but these causal relationships need to be confirmed in additional prospective studies. Currently, there exists neither a standardized SyNC definition nor a dedicated set of imaging protocols, although researchers have started to address these shortcomings. Moreover, many neuroradiologists are still unaware of the condition, and hence do not comment on high-risk plaque features other than stenosis in their reports. Regarding SyNC treatment, scant data exist as to whether and to what extent medical, interventional and surgical treatments could influence the course of the disease; the relative lack of data on the ‘natural’ history of untreated SyNC makes treatment comparisons difficult. In our opinion, endovascular SyNC treatment represents the most promising treatment option for SyNC, since it allows for targeted elimination of the embolic source, with few systemic side effects and without the need for general anesthesia. However, currently available carotid devices are designed to treat stenotic lesions, and thus are not optimally designed for SyNC. Developing a device specifically tailored to SyNC could be an important step towards establishing endovascular SyNC treatment in clinical practice. In this review, we provide an overview of the current state of evidence with regard to epidemiological, clinical and imaging features of SyNC, propose a SyNC definition based on imaging and clinical features, and outline a possible pathway towards evidence-based SyNC therapies, with a special focus on endovascular SyNC treatment.

Background Federal research funding is highly sought after but may be challenging to attain. A clear understanding of funding for specific diseases, such as cerebrovascular disorders, might help researchers regarding which National Institutes of Health (NIH) institutes fund research into specific disorders and grant types. Objective To examine the current scope of NIH grant funding for cerebrovascular conditions. Methods The NIH-developed RePORTER was used to extract active NIH-funded studies related to cerebrovascular diseases through January 2023. Duplicate studies were removed, and projects were manually screened and labeled in subcategories as clinical and basic science and as research subcategories. Extracted data included total funding, grant types, institutions that received funding, and diseases studied. Python (version 3.9) and SciPy library were used for statistical analyses. Results We identified 1232 cerebrovascular projects across seven diseases with US$699 952 926 in total funding. The cerebrovascular diseases with the greatest number of grants were ischemic stroke (705, or 57.2% of all funded projects), carotid disease (193, or 15.7%), and hemorrhagic stroke (163, or 13.2%). R01 grants were the most common mechanism of funding (632 grants, or 51.3%). The National Institute of Neurological Disorders and Stroke (NINDS) funded the most projects (504 projects; US$325 536 405), followed by the National Heart, Lung, and Blood Institute (NHLBI) (376 projects; US$216 784 546). Conclusion Cerebrovascular disease receives roughly US$700 million in NIH funding. Ischemic stroke accounts for the majority of NIH-funded cerebrovascular projects, and R01 grants are the most common funding mechanism. Notably, NHLBI provides a large proportion of funding, in addition to NINDS.

Aim: Stent-retriever (SR) thrombectomy has demonstrated superior outcomes in patients with acute ischemic stroke compared with medical management alone, but differences among SRs remain unexplored. We conducted a Systematic Review/Meta-Analysis to compare outcomes between three SRs: EmboTrap ® , Solitaire™, and Trevo ® . Methods: We conducted a PRISMA-compliant Systematic Review among English-language studies published after 2014 in PubMed/MEDLINE that reported SRs in ≥25 patients. Functional and safety outcomes included 90-day modified Rankin scale (mRS 0-2), mortality, symptomatic intracranial hemorrhage (sICH), and embolization to new territory (ENT). Recanalization outcomes included modified thrombolysis in cerebral infarction (mTICI) and first-pass recanalization (FPR). We used a random effects Meta-Analysis to compare outcomes; subgroup and outlier-influencer analysis were performed to explore heterogeneity. Results: Fifty-one articles comprising 9,804 patients were included. EmboTrap had statistically significantly higher rates of mRS 0-2 (57.4%) compared with Trevo (50.0%, p = 0.013) and Solitaire (45.3%, p < 0.001). Compared with Solitaire (20.4%), EmboTrap (11.2%, p < 0.001) and Trevo (14.5%, p = 0.018) had statistically significantly lower mortality. Compared with Solitaire (7.7%), EmboTrap (3.9%, p = 0.028) and Trevo (4.6%, p = 0.049) had statistically significantly lower rates of sICH. There were no significant differences in ENT rates across all three devices (6.0% for EmboTrap, 5.3% for Trevo, and 7.7% for Solitaire, p = 0.518). EmboTrap had numerically higher rates of recanalization; however, no statistically significant differences were found. Conclusion: The results of our Systematic Review/Meta-Analysis suggest that EmboTrap may be associated with significantly improved functional outcomes compared with Solitaire and Trevo. EmboTrap and Trevo may be associated with significantly lower rates of sICH and mortality compared with Solitaire. No significant differences in recanalization and ENT rates were found. These conclusions are tempered by limitations of the analysis including variations in thrombectomy techniques in the field, highlighting the need for multi-arm RCT studies comparing different SR devices to confirm our findings.

Background As the myriad clinical and radiographic presentations of spontaneous intracranial hypotension are increasingly recognized, disease prevalence appears to rise. True incidence data remain insufficient. We sought to calculate the incidence of spontaneous intracranial hypotension among the residents of Olmsted County, Minnesota. Methods Our institution is a quaternary care center for spontaneous intracranial hypotension evaluation and provides primary neurologic care for local residents. All patients who were evaluated at our institution from 2019 to 2021 for spontaneous intracranial hypotension were reviewed, and cases of spontaneous intracranial hypotension with advanced imaging work-up using digital subtraction myelography or dynamic computed tomography myelography were identified. Patients who were residents of Olmsted County were identified. Results Fourteen patients with spontaneous intracranial hypotension were identified in Olmsted County during the study period, all of whom were adults and underwent our institution's standard spontaneous intracranial hypotension work-up. In Olmsted County, the incidence of spontaneous intracranial hypotension was 3.8 per 100,000 adult population, including 3.2 per 100,000 adult females and 2.5 per 100,000 adult males. Seven of 14 patients (50%) had a cerebrospinal fluid-venous fistula. Conclusion This study uniquely presents the incidence rate of spontaneous intracranial hypotension in the general population of Olmsted County, Minnesota. Spontaneous intracranial hypotension is more common in women than men and has an overall incidence roughly equivalent to that of aneurysmal subarachnoid hemorrhage in Olmsted County, a widely known neurologic condition. Approximately half the cases of spontaneous intracranial hypotension are due to cerebrospinal fluid-venous fistulas, which generally require specialty expertise for diagnosis and treatment.

Background The recognition of venous sinus stenosis as a contributing factor in the majority of patients with idiopathic intracranial hypertension coupled with increasing cerebral venography and venous sinus stenting experience have dramatically improved our understanding of the pathophysiologic mechanisms driving this disease. There is now a dense, growing body of research in the neurointerventional literature detailing anatomical and physiological mechanisms of disease which has not been widely disseminated among clinicians. Methods A literature search was conducted, covering the most recent neurointerventional literature on idiopathic intracranial hypertension, the pathophysiology of idiopathic intracranial hypertension, and management strategies (including venous sinus stenting), and subsequently summarized to provide a comprehensive review of the most recently published studies on idiopathic intracranial hypertension pathophysiology and management. Conclusion Recent studies in the neurointerventional literature have greatly improved our understanding of the pathophysiologic mechanisms causing idiopathic intracranial hypertension and its associated conditions. The ability to make individualized, patient-specific treatment approaches has been made possible by advances in our understanding of how venous sinus stenosis and cerebral venous hypertension fundamentally contribute to idiopathic intracranial hypertension.