Gaps in the access to endovascular thrombectomy for acute ischaemic stroke: estimating neurointerventional training needs and modelling implementation impact based on current thrombectomy indicators

Marc Fisher MD Kennedy Lees MD Section Editors: On September 26, 2008, the New England Journal of Medicine published the results of the European Cooperative Stroke Study (ECASS) III,1 the first randomized, placebo-controlled trial to demonstrate safe and effective use of intravenous recombinant tissue plasminogen activator (rtPA) to treat patients with acute ischemic stroke (AIS) beyond 3 hours from stroke onset. The ECASS investigators studied the safety and efficacy of administering intravenous rtPA to patients with AIS 3 to 4.5 hours after AIS onset. Using the modified Rankin Scale score at 90 days after stroke occurrence as the primary end point of the study, the investigators demonstrated a modest, statistically significant increase in the likelihood of having normal or near normal recovery (modified Rankin Scale=0 or 1) in favor of rtPA treatment compared with placebo (unadjusted OR, 1.34; 95% CI, 1.02 to 1.76; P =0.04). So, what impact will the results of the study have on acute stroke management and stroke research in the United States and elsewhere? With regard to the first part of the question, the answer is complex. First, the ECASS III results will hopefully help to increase the number of thrombolysis eligible patients with AIS who receive rtPA. Twelve years after the US Food and Drug Administration approved the management of AIS within 3 hours of symptom onset as an indication for the use of intravenous rtPA, less than 5% of patients with AIS are being treated worldwide with rtPA within 3 hours of stroke onset. One of the major factors contributing to this parlous state of affairs has been disagreement among healthcare professionals about the validity of the results of the National Institutes of Neurological Disorders and Stroke (NINDS) trial of rtPA for acute stroke.2 In the late 1990s, the stroke community unexpectedly …

A 42-year-old woman was referred to our institution with sudden onset of ataxia, facial paresis, horizontal gaze palsy, and progressive dysarthria. The patient worsened within a few minutes, with appearance of left hemiparesis. The National Institutes of Health Stroke Scale Score was 13. On computer tomography scan 2 hours after stroke onset, no brain stem lesion or intracranial bleeding was visible. Computed tomographic angiography revealed a mid basilar vessel occlusion, which suggested embolic basilar artery occlusion. A 4-vessel angiogram with a 5F diagnostic catheter confirmed the basilar artery occlusion and depicted more precisely the location of the thrombus (Figure 1A). Figure 1. A, Digital subtraction angiography after vertebral injection demonstrates a mid basilar vessel occlusion. B, The angiogram after placement of the stent from the left P1 segment (white arrow) into the basilar artery showed flow restoration of the basilar artery with a narrowing in the middle part of the vessel due to compression of the thrombus into the arterial wall (black arrows). C, …

Section Editors: Marc Fisher MD Antoni Davalos MD The Food and Drug Administration (FDA) evaluates applications for new human drugs, biologics, and complex medical devices. Companies must obtain FDA approval to legally market these products. In August, the FDA gave Concentric Medical clearance to market its Merci Retriever system to “remove blood clots from the brain in patients experiencing an ischemic stroke.” Given that the FDA is charged with “protecting the public health by assuring the safety, efficacy, and security of… biological products and medical devices…, ” “advancing public health by helping to speed innovations that make medicines … more effective, safer, and more affordable,” and “helping the public get the accurate, science-based information they need to use medicines … to improve their health,”1 the FDA’s decision to approve the Merci Retriever system is of concern. The pathways to approval are reviewed by Felten et al in the accompanying article and are outlined in Figure 1. Figure 1. Potential pathways for device approval. The decision to approve the Merci Retriever was based on data from the MERCI (Mechanical Embolus Removal in Cerebral Ischemia) Trial; the approval was granted through the 510(k) process. The Merci Retriever system includes a flexible nickel titanium (nitinol) wire that obtains a helical shape once it is passed through the tip of the guidance catheter. In practice, the catheter/wire is passed distal to the thrombus, the catheter is removed, and the helical configuration assumed by the wire; the clot is then trapped in the helix and withdrawn from the vasculature (Figure 2). The 510(k) clearance means that the Merci Retriever was felt to be substantially equivalent to a predicate device. In this case, the predicate device was the Concentric Retriever, which itself received 510(k) clearance by the FDA in May 2001 for “use in …

Mobile Stroke Units and Pursuit of Intravenous Tissue-Type Plasminogen Activator Treatment in the Golden Hour.

The association between socioeconomic status and acute ischemic stroke treatments remain uncertain, particularly in countries with universal health care systems. This study aimed to investigate the association between neighborhood-level material deprivation and the odds of receiving IV thrombolysis or thrombectomy for acute ischemic stroke within a single-payer, government-funded health care system. We conducted a population-based cohort study using linked administrative data from Ontario, Canada. This study involved all community-dwelling adult Ontario residents hospitalized with acute ischemic stroke between 2017 and 2022. Neighborhood-level material deprivation, measured in quintiles from least to most deprived, was our main exposure. We considered the receipt of thrombolysis or thrombectomy as the primary outcome. We used multivariable logistic regression models adjusted for baseline differences to estimate the association between material deprivation and outcomes. We performed a sensitivity analysis by additionally adjusting for hospital type at initial assessment. Furthermore, we tested whether hospital type modified the associations between deprivation and outcomes. Among 57,704 patients, those in the most materially deprived group (quintile 5) were less likely to be treated with thrombolysis or thrombectomy compared with those in the least deprived group (quintile 1) (16.6% vs 19.6%, adjusted odds ratio [aOR] 0.76, 95% CI 0.63-0.93). The association was consistent when evaluating thrombolysis (13.0% vs 15.3%, aOR 0.78, 95% CI 0.64-0.96) and thrombectomy (6.4 vs 7.8%, aOR 0.73, 95% CI 0.59-0.90) separately. There were no statistically significant differences between the middle 3 quintiles and the least deprived group. These associations persisted after additional adjustment for hospital type, and there was no interaction between material deprivation and hospital type (p interaction >0.1). We observed disparities in the use of thrombolysis or thrombectomy for acute ischemic stroke by socioeconomic status despite access to universal health care. Targeted health care policies, public health messaging, and resource allocation are needed to ensure equitable access to acute stroke treatments for all patients.

To present a global overview of the current research landscape and emerging trends in mechanical thrombectomy for acute ischemic stroke (AIS) over the past decade. A thorough search was conducted on the Web of Science on May 20, 2024, focusing on original articles and reviews in English. Bibliometric tools were employed to make a network analysis and visual representation. Additionally, data on disability-adjusted life years, prevalence, and incidence of ischemic strokes were extracted from the Global Burden of Disease database. A total of 7776 papers were included, indicating a steady increase from 169 to 1311 between 2014 and 2023. The United States led in core publications with 2887 papers. The incidence and disability-adjusted life years of ischemic stroke have continued to rise in Asia but have recently declined in North America and European countries. The University of Calgary emerged as the leading institution and Mayank Goyal was the most prolific author. Neurointerventional Surgery was the top contributing journal with 790 articles. The analysis identified 6332 keywords forming 5 clusters, with "mechanical thrombectomy" serving as the largest cluster, focusing mainly on interventional thrombectomy techniques for AIS. The term "tissue plasminogen activator" exhibited strong burst strength of 46.58. Keywords such as "injury", "diagnosis", "posterior circulation", and "severity" burst in 2020 and lasted until2024. Interest in mechanical thrombectomy for AIS was progressively increasing. Future research directions may include minimizing intraoperative injuries, refining diagnostic techniques, investigating interventions for posterior circulation, and tailoring thrombectomy strategies based on stroke severity and large vessel occlusion etiology.

Background: Randomized trials have shown that mechanical thrombectomy improves 3-month disability outcomes after acute ischemic stroke for both women and men. However post-stroke disability and reduced life expectancy (LE) persists beyond 3 months, and lifetime effects of thrombectomy might differ between men and women. Methods: We analyzed patients treated with the Solitaire stent retriever in the TripleS database (pooled patient-level data from the SWIFT, STAR, and SWIFT-PRIME trials). Years of optimum life after thrombectomy were defined as disability adjusted life-year (DALYs), using the methodology of the World Health Organization Global Burden of Disease Project. For each patient, LE was calculated based on age and sex-specific values, and known degree of modification of LE by modified Rankin Scale (mRS) status at 3 months post-stroke. Years of optimum life lost due to disability were calculated by projecting mRS status at 3 months through the remaining LE. Results: Among 389 patients treated with ET, 55% were female, and median NIHSS was 17 [8-28]. There were no differences between females vs. males in presenting deficit severity (NIHSS 17 vs. 17, p=0.21), occlusion location (69% vs. 64% M1, p=0.62), presenting infarct extent (ASPECTS 9 vs. 8, p=0.24), rate of substantial reperfusion (TICI 2b/3, 87% vs. 83%, p=0.37), onset to reperfusion time (277 vs. 306 mins, p=0.46). Women presented at advanced mean age compared to men (69 vs 64, p<0.001). Rates of functional independence at 90 days (53% vs. 56%, p=0.54) were similar in men and women. Without adjusting for age at presentation, years of optimal life (DALYs) following thrombectomy were similar between women and men (9.3 vs 9.6 years, p=0.48). After adjusting for differing ages at presentation, women had more years of optimal life (DALYs) following thrombectomy, 10.6 vs 8.5 years (p<0.001). Conclusions: In age-standardized comparisons, women experience two more optimal years than men following mechanical thrombectomy for acute ischemic stroke. Greater life expectancies of women, coupled with similar disability outcome distributions, yield substantially greater years of optimal life after intervention.

The original version of this consensus statement on mechanical thrombectomy was approved at the European Stroke Organisation (ESO)-Karolinska Stroke Update conference in Stockholm, 16-18 November 2014. The statement has later, during 2015, been updated with new clinical trials data in accordance with a decision made at the conference. Revisions have been made at a face-to-face meeting during the ESO Winter School in Berne in February, through email exchanges and the final version has then been approved by each society. The recommendations are identical to the original version with evidence level upgraded by 20 February 2015 and confirmed by 15 May 2015. The purpose of the ESO-Karolinska Stroke Update meetings is to provide updates on recent stroke therapy research and to discuss how the results may be implemented into clinical routine. Selected topics are discussed at consensus sessions, for which a consensus statement is prepared and discussed by the participants at the meeting. The statements are advisory to the ESO guidelines committee. This consensus statement includes recommendations on mechanical thrombectomy after acute stroke. The statement is supported by ESO, European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), and European Academy of Neurology (EAN).

The use of heparin during mechanical thrombectomy (MT) for acute large vessel occlusion ischemic stroke (LVO-AIS) is controversial, with no unified standard on its administration methods and efficacy. This study aims to investigate the effectiveness and safety of continuous intra-arterial infusion of heparin administration during MT in real-world practice. A single-center retrospective study included consecutive LVO stroke patients treated with mechanical thrombectomy at Chongqing University Central Hospital (August 2022-January 2024). Participants were stratified by intraprocedural heparin administration: (1) arterial heparin Group-continuous intra-arterial heparinization via high-pressure infusion (Heparin 1,000 IU was diluted in 500 ml of 0.9% sodium chloride solution and connected to both the guiding catheter and the intermediate catheter. The infusion bag was replaced as needed according to the duration of the procedure) at a conventional drip rate; (2) non-additional heparin Group-standard heparin solution flushing withoutusing additional anticoagulant. The main outcome were 3-months functional independence, defined as a modified Rankin Scale (mRS) ≤ 2. The main Safety outcome were defined as symptomatic intracranial hemorrhage (sICH) in 24 h. A total of 98 patients were eligible for analysis: 54 in the Arterial heparin Group and 44 in the Non-additional heparin Group. Continuous intra-arterial infusion of heparin administration during MT had a higher rates of functional independence (57.4 vs. 36.4%, adjusted P = 0.035), no significant impact on recanalization rate, sICH, distal embolization, or mortality (adjusted P > 0.05). However, the admission NIHSS score [odds ratio 1.225 (1.096-1.370), P < 0.01] was identified as independent predictor of unfavorable outcomes, while anticoagulant therapy during hospitalization [odds ratio 0.209 (0.067-0.653), P < 0.01] was a protective factor. Aspiration was a protective factor against sICH [odds ratio 0.009 (0.00-0.845), P = 0.042]. Our study suggests that continuous intra-arterial infusion of heparin administration during mechanical thrombectomy for acute large vessel occlusion ischemic stroke may be safe and is associated with higher rates of favorable outcomes. Further prospective research is needed to validate these findings.

BackgroundLeukoaraiosis (LA) severity is associated with poor outcome after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) caused by large vessel occlusion. This meta-analysis aimed to assess the association of LA severity with AIS-related risk factors and outcomes of MT.MethodsPubMed, Web of Science, EMBASE, and Cochrane Collaboration Database was searched for studies on MT for AIS with LA. We conducted a random-effects meta-analysis for the prevalence of stroke risk factors and the MT outcome in the absent to moderate LA and severe LA groups.ResultsWe included seven cohort studies involving 1294 participants (1019 with absent to moderate LA and 275 with severe LA). The absent to moderate LA group had a significantly lower prevalence of coronary artery disease (odds ratio [OR] 0.43; 95% CI 0.29–0.66), atrial fibrillation (OR, 0.26; 95% CI 0.17–0.38), hypertension (OR, 0.39; 95% CI 0.24–0.61), and ischemic stroke (OR, 0.27; 95% CI 0.15–0.50) than the severe LA group. There were no significant between-group differences in symptom onset to recanalization time (364.4 versus 356.2 min, mean difference 19.4; 95% CI − 28.3 to 67.2), final recanalization rate (modified thrombolysis in cerebral infarction score of 2b/3; OR, 0.87; 95% CI 0.55–1.38), and symptomatic intracranial hemorrhage (OR, 0.62; 95% CI 0.34–1.11). The absent to moderate LA group had a higher good functional outcome (modified Rankin Scale score of 0–2 at 90 days; OR, 4.55; 95% CI 3.20–6.47) and a lower mortality rate (179/1019 vs 108/275; OR, 0.28; 95% CI 0.20–0.39).ConclusionThere are unique differences in the characteristics of risk factors and clinical outcomes of ischemic stroke across patients with LA of different severity. Patients with severe LA are more likely to be associated with risk factors for cerebrovascular disease and have a poor post-MT outcome.

Background and Purpose- We determined the effect of sex on outcome after endovascular stroke thrombectomy in acute ischemic stroke, including lifelong disability outcomes. Methods- We analyzed patients treated with the Solitaire stent retriever in the combined SWIFT (Solitaire FR With the Intention for Thrombectomy), STAR (Solitaire FR Thrombectomy for Acute Revascularization), and SWIFT PRIME (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment) cohorts. Ordinal and logistic regression were used to examine known factors influencing outcome after endovascular stroke thrombectomy and study the effect of sex on the association between these factors and outcomes, including age and time to reperfusion. Years of optimal life after thrombectomy were defined as disability-adjusted life years and calculated by projecting disability through adjusted poststroke life expectancy by sex. Results- Among 389 patients treated with endovascular stroke thrombectomy, 55% were females, and median National Institutes of Health Stroke Scale was 17 (interquartile range, 8-28). There were no differences between females versus males in presenting deficit severity (National Institutes of Health Stroke Scale score, 17 versus 17, P=0.21), occlusion location (69% versus 64% M1, P=0.62), presenting infarct extent (Alberta Stroke Program Early CT Score 8 versus 8, P=0.24), rate of substantial reperfusion (Thrombolysis in Cerebral Infarction 2b/3, 87% versus 83%, P=0.37), onset to reperfusion time (294 versus 302 minutes, P=0.46). Despite older ages (69 versus 64, P<0.001) and higher rate of atrial fibrillation (45% versus 30%, P=0.002) for females compared with males, adjusted rates of functional independence at 90 days were similar (odds ratio, 1.0; 95% CI, 0.6-1.6). After adjusting for age at presentation and stroke severity, females had more years of optimal life (disability-adjusted life year) after endovascular stroke thrombectomy, 10.6 versus 8.5 years (P<0.001). Conclusions- Despite greater age and higher rate of atrial fibrillation, females experienced comparable functional outcomes and greater years of optimal life after intervention compared with males.

The management of tandem extracranial internal carotid artery and intracranial large vessel occlusion during endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) has been under-investigated. We sought to investigate outcomes of AIS patients with tandem occlusion (TO) treated with carotid artery stenting (CAS) compared to those not treated with CAS (no-CAS) during EVT. We performed a cohort study using data from AIS patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. Outcomes were 3months' mortality, functional outcome, complete and successful recanalization, any intracranial hemorrhage, parenchymal hematoma and symptomatic intracerebral hemorrhage. Among 466 AIS patients with TO, CAS patients were 122 and no-CAS patients were 226 (118 excluded). After adjustment for unbalanced variables, CAS was associated with a lower rate of 3months' mortality (OR 0.407, 95% CI 0.171-0.969, p = 0.042). After adjustment for pre-defined variables, CAS was associated with a lower rate of 3months' mortality (aOR 0.430, 95% CI 0.187-0.989, p = 0.047) and a higher rate of complete recanalization (aOR 1.986, 95% CI 1.121-3.518, p = 0.019), successful recanalization (aOR 2.433, 95% CI 1.263-4.686, p = 0.008) and parenchymal hematoma (aOR 2.876, 95% CI 1.173-7.050, p = 0.021). CAS was associated with lower 3months mortality (OR 0.373, 95% CI 0.141-0.982, p = 0.046) and higher rates of successful recanalization (OR 2.082, 95% CI 1.099-3.942, p = 0.024) after adjustment for variables associated with 3months' mortality and successful recanalization, respectively. Among AIS patients with TO, CAS during EVT was associated with a higher rate of successful reperfusion and a lower rate of 3months' mortality.

Background: The impact of anesthesia technique on the outcomes of mechanical thrombectomy for acute ischemic stroke remains an issue of debate, and has not been studied in clinical trials. We investigated the association of general anesthesia with outcomes in patients undergoing mechanical thrombectomy for ischemic stroke. Methods: We performed a cohort study involving patients undergoing mechanical thrombectomy for ischemic stroke from 2009-2013, who were registered in the New York Statewide Planning and Research Cooperative System (SPARCS) database. An instrumental variable (hospital rate of general anesthesia) analysis was used to simulate the effects of randomization and investigate the association of anesthesia technique with case-fatality and length of stay (LOS). Results: Of the 1,308 patients undergoing mechanical thrombectomy for acute ischemic stroke, 492 (37.6%) underwent general anesthesia, and 816 (62.4%) underwent conscious sedation. Employing an instrumental variable analysis, we identified that general anesthesia was associated with a 6.4% increased case-fatality (95% CI, 1.9% to 11.0%), and 8.4 days longer LOS (95% CI, 2.9 to 14.0) in comparison to conscious sedation. This corresponded to 15 patients needing to be treated with conscious sedation to prevent one death. Our results were robust in a sensitivity analysis utilizing mixed effects regression, and propensity score adjusted regression models. Conclusions: Using a comprehensive all-payer cohort of acute ischemic stroke patients undergoing mechanical thrombectomy in New York State, we identified an association of general anesthesia with increased case fatality and LOS. These considerations should be taken into account when standardizing acute stroke care.

OBJECTIVE As the cost of health care continues to increase, there is a growing emphasis on evaluating the relative economic value of treatment options to guide resource allocation. The objective of this systematic review was to evaluate the current evidence regarding the cost-effectiveness of cranial neurosurgery procedures. METHODS The authors performed a systematic review of the literature using PubMed, EMBASE, and the Cochrane Library, focusing on themes of economic evaluation and cranial neurosurgery following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Included studies were publications of cost-effectiveness analysis or cost-utility analysis between 1995 and 2017 in which health utility outcomes in life years (LYs), quality-adjusted life years (QALYs), or disability-adjusted life years (DALYs) were used. Three independent reviewers conducted the study appraisal, data abstraction, and quality assessment, with differences resolved by consensus discussion. RESULTS In total, 3485 citations were reviewed, with 53 studies meeting the inclusion criteria. Of those, 34 studies were published in the last 5 years. The most common subspecialty focus was cerebrovascular (32%), followed by neurooncology (26%) and functional neurosurgery (24%). Twenty-eight (53%) studies, using a willingness to pay threshold of US$50,000 per QALY or LY, found a specific surgical treatment to be cost-effective. In addition, there were 11 (21%) studies that found a specific surgical option to be economically dominant (both cost saving and having superior outcome), including endovascular thrombectomy for acute ischemic stroke, epilepsy surgery for drug-refractory epilepsy, and endoscopic pituitary tumor resection. CONCLUSIONS There is an increasing number of cost-effectiveness studies in cranial neurosurgery, especially within the last 5 years. Although there are numerous procedures, such as endovascular thrombectomy for acute ischemic stroke, that have been conclusively proven to be cost-effective, there remain promising interventions in current practice that have yet to meet cost-effectiveness thresholds.

In the acutely infarcted brain, cytokines are released into cerebrospinal fluid and blood. Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, among others, may play a role in the acute increases in plasma adrenocorticotropic hormone, cortisol, epinephrine, norepinephrine, and vasopressin.1–6 Increases in cytokines and hormones may in turn induce changes in other variables. When recorded on admission in acute stroke patients, many variables have been found to be associated with poor outcome in acute stroke. Body temperature7 is one such variable, blood glucose another,8–18 and C-reactive protein (CRP)19–22 and white blood cell count (WBC)20,23 serum cortisol and ferritin24 are further examples. Elevated plasma and cerebrospinal fluid levels of glutamate, glycine,25 ferritin,26 and IL-627 were also associated with deteriorating stroke. It seems plausible that these variables generally are unaffected at stroke onset and then increase in the early hours after onset, depending on the severity of the stroke. We found this to be the case with temperature,28 which in a large series of patients was normal when measured within 2 hours of stroke onset, but which rose at 4 to 6 hours after stroke onset in patients with severe neurological deficits. At 8 to 10 hours after stroke onset, elevated temperature was associated with poor outcome. This association arose several hours after onset of severe stroke. Thus, the initial severity of the stroke …