Skip to main content
AAN.com
Endovascular Therapy
November 16, 2021
Free Access

Indications for Mechanical Thrombectomy for Acute Ischemic Stroke
Current Guidelines and Beyond

November 16, 2021 issue
97 (20_Supplement_2) S126-S136

Abstract

Purpose of the Review

This article reviews recent breakthroughs in the treatment of acute ischemic stroke, mainly focusing on the evolution of endovascular thrombectomy, its impact on guidelines, and the need for and implications of next-generation randomized controlled trials.

Recent Findings

Endovascular thrombectomy is a powerful tool to treat large vessel occlusion strokes and multiple trials over the past 5 years have established its safety and efficacy in the treatment of anterior circulation large vessel occlusion strokes up to 24 hours from stroke onset.

Summary

In 2015, multiple landmark trials (MR CLEAN, ESCAPE, SWIFT PRIME, REVASCAT, and EXTEND IA) established the superiority of endovascular thrombectomy over medical management for the treatment of anterior circulation large vessel occlusion strokes. Endovascular thrombectomy has a strong treatment effect with a number needed to treat ranging from 3 to 10. These trials selected patients based on occlusion location (proximal anterior occlusion: internal carotid or middle cerebral artery), time from stroke onset (early window: up to 6–12 hours), and acceptable infarct burden (Alberta Stroke Program Early CT Score [ASPECTS] ≥6 or infarct volume <50 mL). In 2017, the DAWN and DEFUSE-3 trials successfully extended the time window up to 24 hours in appropriately selected patients. Societal and national thrombectomy guidelines have incorporated these findings and offer Class 1A recommendation to a subset of well-selected patients. Thrombectomy ineligible stroke subpopulations are being studied in ongoing randomized controlled trials. These trials, built on encouraging data from pooled analysis of early trials (HERMES collaboration) and emerging retrospective data, are studying large vessel occlusion strokes with mild deficits (National Institutes of Health Stroke Scale <6) and large infarct burden (core volume >70 mL).

Reperfusion Hypothesis

Cerebral ischemia occurs when a blood vessel hypoperfuses the target tissue. The target tissue subsequently undergoes irreversible damage in a time dependent fashion with dead tissue referred to as “core” and at-risk tissue referred to as “penumbra.” The reperfusion hypothesis posits that the penumbra is salvageable tissue that can be rescued with expeditious and complete restoration of blood flow. Conversely, failure to restore blood flow inevitably results in the surrender of penumbral tissue to irreversible damage and expansion of the core. Early attempts to both intravenously and intra-arterially reinstate perfusion established proof of concept but safety and efficacy required further refinement. After numerous negative thrombolysis trials, the results of the NINDS tpa trial in 1995 demonstrated the superiority of IV tPA over placebo in patients presenting within 3 hours of symptoms.1 This prompted the Food and Drug Administration (FDA) to approve the use of IV tPA up to 3 hours in 1996. While subsequent studies such as the ECASS3 trial in 2008 further demonstrated the benefit of IV tPA over placebo in patients presenting within 3–4.5 hours of symptoms,2 the FDA did not find this data sufficient to grant supplemental biological license and the current on-label indication for IV tPA remains restricted to 3 hours.3
While the intravenous approach is more easily administrable and therefore more broadly available, the limited therapeutic time window as well as low efficacy13 for large vessel occlusions prompted interest in an endovascular approach. The Prolyse in Acute Cerebral Thromboembolism (PROACT I) trial enrolled patients presenting with a middle cerebral artery (MCA) occlusion within 6 hours of symptoms onset. Patients were randomized to local intra-arterial infusion of thrombolysis (r-proUK) vs saline. The trial was halted early due to the approval of IV tPA, however analysis revealed higher rates of recanalization with r-proUK (57.7%) vs placebo (14.3%). This landmark study was the first randomized controlled trial investigating the benefit of an intra-arterial approach for acute ischemic stroke and laid the groundwork for future investigations.14
Based on the encouraging results of PROACT I, the PROACT II study randomized a larger set of patients with MCA occlusions presenting within 6 hours of symptoms onset to receive a local infusion of r-proUK vs placebo over a 2-hour period.15 Both groups received low dose intravenous heparin (in PROACT I and II). Once again, higher rates of recanalization were noted in the lytic cohort and while there were higher rates of symptomatic hemorrhage in the treatment population, there was improved outcomes in the r-proUK group (40%) compared to the placebo group (25%). Despite the positive primary outcome, the FDA ultimately did not approve the use of r-proUK due to the small study sample size. In the first AHA/ASA acute ischemic stroke guidelines in 1994,16 intra-arterial therapy was considered investigational with level E evidence but in 2003,17 the results of PROACT II were extrapolated to alteplase based on consensus as supported by case series data.
An additional study conducted in Japan from 2002 to 2005 compared the efficacy of intra-arterial urokinase vs placebo for patients presenting within 6 hours of symptoms. This study was halted after the approval of IV tpa in Japan. Good outcomes were more frequent in the treatment arm; however, the results did not reach statistical significance due to limited sample size.18 In clinical practice terms, the results of these studies were extrapolated to tPA and this led to increased use of intra-arterial therapy, particularly in patients who did not respond to or qualify for IV tpa.

First Generation Technique Trials

To some extent, the promising experience with PROACT II and MELT likely led to some loss of equipoise among practitioners and thereby created barriers to conducting further randomized controlled trials. Nonetheless, the PROACT II introduced several important concepts relevant to future study design including the utilization of dichotomized modified Rankin Scale (mRS) of 0–2 as a primary end-point for an acute ischemic stroke trial as well as expanding the treatment time window from 3 hours to 6 hours.15
Given lingering concerns of hemorrhagic complications associated with lytics, the development of mechanical devices for clot disruption and retrieval became of high interest. Several classes of devices were developed including lasers, ultrasonography, angioplasty and micro-snares. In 2004, FDA cleared the Merci retriever which consisted of a memory-shaped nitinol wire with helical loops that was delivered to the thrombus via microcatheter navigation. Approval was based on a single arm, prospective study of patients who presented within 8 hours of symptoms onset and were ineligible for IV tpa. Recanalization was achieved in 46% of patients and good outcomes were more frequent in the patients who experienced successful recanalization (46% vs 10%, p < 0.0001).19 Since the data was not a randomized comparison to a medical therapy, the FDA granted the 510K-pathway for clearance as a device for clot removal in acute ischemic stroke, however not for a clinical indication for reduced disability. Modelled after the reimbursement for craniectomy, the device company was successfully able to negotiate a diagnosis-related group reimbursement through the Centers for Medicare & Medicaid Services. The 510-k pathway was successfully pursued in 2007 for a second class of devices: reperfusion catheters with aspiration pump. This was based on the results of the single arm prospective pivotal Penumbra trial which enrolled patients who were ineligible or refractory to IV tpa presenting within 8 hours of symptoms onset.20 The use of mechanical thrombectomy was supported by a class II level B recommendation by the AHA/ASA.21
While intra-arterial therapy became increasingly available, there was no high-quality data to suggest that this approach was any more efficacious than medical therapy. Given the associated cost and variable availability, EVT was offered sporadically and the use of mechanical thrombectomy as of 2013 was only supported by a class II level B recommendation by the AHA/ASA.21 Three randomized controlled trials (IMS III, SYNTHESIS, MR RESCUE) were conducted to address the question of whether EVT as stand-alone or adjunctive therapy would lead to superior outcomes over IVT in patients presenting with acute ischemic stroke.22-24 While all the studies had slightly different trial designs, a majority of patients were treated with first generation technology (intra-arterial alteplase, Merci retriever, Penumbra reperfusion catheter) with resultant low rates of recanalization. Additional trial limitations included: inclusion of patients without proven occlusion (lack of surgical target lesion in approximately 8% of patients) and established infarct (minimal salvageable tissue) as well as slow work flow. Furthermore, there was often failure to randomize all consecutive eligible patients, likely reflecting provider lack of equipoise. While the results were disappointing, the lessons learned galvanized efforts to design a second wave of trials focused primarily on more efficacious devices, appropriate patient selection and streamlined workflow.

Stent Retriever Devices

In order to appropriately test the reperfusion hypothesis, a basic prerequisite is that vessel recanalization is achieved with complete (TICI3) or near complete recanalization (TICI2b). A major limitation of the first-generation devices was low efficacy with recanalization. For example, successful recanalization after thrombectomy in the IMS3 trial was only 44% and even less in the MR RESCUE trial (27%). The rates of recanalization in the SYNTHESIS trial were not reported.22-24 Given the relatively low efficacy of intra-arterial thrombolysis with LVO,14,15 the MERCI retriever and first-generation Penumbra aspiration catheters, continued interest remained in further refining the mechanical thrombectomy approach. In cases where vessels could not be recanalized with available technologies, practitioners began resorting to angioplasty and intra-cranial stent placement as salvage methods. While there was technical success in opening the vessel, the need for subsequent dual anti-platelets to preserve implant patency complicates routine use of this approach given concerns for hemorrhagic complications. Nonetheless, the general principle of radially displacing the whole length of thrombus against the vessel wall while simultaneously incorporating the clot in the stent struts prompted the development of a new class of stent-like devices termed stent retrievers. Importantly, stent retrievers are subsequently withdrawn from the intra-cranial vasculature after clot engagement without significant vessel disruption and abrogate the need for dual antiplatelets.
The Solitaire Flow Restoration device is a self-expanding stent retriever that was compared to the predicate Merci retriever device in the SWIFT study.25 Rates of recanalization (TIMI 2 or 3) were significantly higher with the Solitaire device (61% vs 24%). A second stent retriever device, the Trevo retriever, was similarly compared against the Merci retriever device. Rates of recanalization (TICI 2 or higher) were significantly higher with the Trevo device (86% vs 60%).26 Superior clinical outcomes were observed in the stent retriever arm of both studies. The use of stent retriever devices over the Merci retriever for clot retrieval were supported by a class I level A recommendation by the 2013 AHA/ASA guidelines.21 Given the results of the SWIFT study and the TREVO2 study, both devices were cleared by the FDA in 2014. Similar to the Merci and Penumbra devices, the stent retriever devices were initially cleared for clot removal but not for reducing clinical disability.

Early Time Window Trials

Given the improved recanalization rates, a new set of trials, predominantly employing the Solitaire and Trevo devices, studied the benefit of EVT therapy over medical therapy alone. MR CLEAN was a randomized controlled trial performed in the Netherlands that studied 500 patients presenting within 6 hours of symptoms onset related to an intra-cranial anterior circulation occlusion.8 Patients were randomized to receive standard medical management (including IV tpa) alone vs adjunctive EVT. At 24 hours, 75.4% of the patients in the intervention had absence of residual occlusion as compared to 32.9% of the patients in the control group. Importantly, the primary end-point of mRS 0–2 at 90 days was higher in the treatment group (32.6% vs 19.1%) and the follow up infarct volume was smaller by 19 cc on average. This study was the first to demonstrate the benefit of EVT over usual care (including IV tpa).
The favorable results of MR CLEAN compared to IMS III have been attributed to several important study design considerations. In terms of patient selection, MR CLEAN required the documentation of an intra-cranial occlusion whereas initially the use of CTA was not routine during the enrollment of IMS III and vessel status was unknown in 47% of the patients.22 Of patients that underwent mechanical thrombectomy, nearly all cases (190 out of 195) used stent retrievers. In addition, a major concern of IMS III had been the slow enrollment (1–2 patients per center per year) which was attributed in part to treatments being offered outside the context of a clinical trial. This enrollment bias was minimized in MR CLEAN as all centers offering EVT participated in the trial and after policy changes in 2013, insurance reimbursement was only provided for patients being treated in the context of the clinical trial.
After the results of MR CLEAN were presented at the World Stroke Conference in the October of 2014, several ongoing EVT trials were either halted due to lack of equipoise or examined at a pre-specified interim analysis. In short order, the results of EXTEND-IA, ESCAPE, SWIFT PRIME and REVASCAT similarly confirmed the benefit of EVT over medical therapy.4-7 These trials were all published in 2015 and based on these cumulative results, the AHA/ASA guidelines were revised and supported a class I level A recommendation for patients with baseline good functional status (mRS 0–1) and treatment initiation within 6 hours of disabling stroke (NIHSS≥6) due to an anterior circulation proximal occlusion (internal carotid artery, MCA segment 1) and small infarct (Alberta Stroke Program Early CT Score [ASPECTS] of 6 or better) should receive IV tpa and undergo stent retriever thrombectomy.27 In addition, the FDA expanded clearance for stent retrievers from simply clot removal to also reducing disability. The stent retrievers are the first and only class of neurothrombectomy devices cleared for clinical indication.
The rationale for these specific criteria was based on the AHA/ASA Level of Evidence grading algorithm requiring more than one positive trial specifying the various criteria to warrant a level A recommendation: baseline mRS 0–1 (SWIFT PRIME, REVASCAT), treatment within 6 hours (SWIFT PRIME, EXTEND-IA), ASPECTS 6 or better (SWIFT PRIME, ESCAPE) and NIHSS 6 or higher (ESCAPE, REVASCAT). Furthermore, a majority of the trials either excluded or minimally included occlusions involving or distal to the MCA segment 2 (MCA-M2). Table 1 provides trial specific inclusion criteria and Figure 1 provides a figure including the rates of recanalization and rates of functional independence in the intervention arm of early window thrombectomy trials.
Table 1 Frequency of Baseline mRS, ASPECT, and Site of Occlusion by Trial
Figure 1 Rates of Recanalization (TICI≥2B) and mRS 0–2 at 90 Days in Early Window Trials

Late Time Window Trials

While the ESCAPE trial randomized patients up to 12 hours and the REVASCAT trial enrolled patients treatable within 8 hours of time last seen well, very few patients were available from the 2015 clinical trials to determine the benefit of EVT in patients presenting beyond 6 hours of symptoms onset. Indeed, in the MR CLEAN study, benefit was no longer statistically significant if reperfusion occurred after 6 hours and 19 minutes of symptoms onset. A meta-analyses of the 5 trials was conducted as part of the HERMES collaboration (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT) and similarly demonstrated that there was no additional clinical benefit of mechanical thrombectomy after 7.3 hours.28 The benefit of reperfusion therapy is time dependent with the every 30-minute delay in reperfusion leading to a 26% decrease in good outcome in the REVASCAT trial.29
Indeed, time has become well recognized as a treatment effect modifier for both IV and IA therapy and much of the stroke systems of care have evolved around the principle of streamlining workflow and reducing time delays. Nonetheless, it has also been long recognized that a subset of patients benefits from perfusion therapy even at late time windows and EVT has been offered off label routinely. In a single center analyses of patients treated with EVT between 2012 to 2015, 126 patients were treated outside of the AHA/ASA guidelines top tier recommendation and of those, 58% were treated beyond 6 hours.30 The physiologic basis for this approach has been predicated on the clinical observation that patients presenting after similar duration of symptoms onset will have variable established infarct31,32 and therefore a tissue based paradigm has been increasingly adopted in favor of a purely time based paradigm.33,34
In 2011, a multi-center study of 237 patients presenting with an anterior circulation occlusion treated beyond 8 hours of symptoms onset and selected based on perfusion imaging revealed rates of good outcomes comparable to those treated in the early time window with comparable safety profile.34 This “pre-DAWN” cohort of patients served as the rationale for a prospective trial comparing the benefit of EVT vs usual care in patients presenting between 6-24 hours. The DAWN trial was a multi-center study specifically comparing the benefit of Trevo thrombectomy to medical management in late time window patients.10,35 Patients were selected based on severe clinical deficit (high NIHSS) in the setting of a small established infarct (small core). This clinical-core mismatch paradigm successfully identified patients who benefited from EVT in the late time window and the trial was halted after a pre-specified interim analysis. Rate of functional independence at 90 days was 49% in the EVT group as compared with 13% in the control group.10
In 2012, the results of the DEFUSE-2 study demonstrated comparable rates of good outcomes after EVT in patients presenting within 6 hours vs beyond 6 hours as long as a target mismatch was identified on perfusion imaging.36 The target mismatch paradigm served as the basis for patient selection in the DEFUSE-3 trial.11 Similar to the DAWN trial, the DEFUSE-3 trial enrolled patients in the late time window (6–16 hours) with stent retrievers used in a majority of the cases (75%). After the DAWN trial results were presented in the May of 2017, the DEFUSE-3 trial was halted due to lack of equipoise and an early interim analysis at the time confirmed benefit of EVT over medical therapy in patients selected based on a tissue paradigm. Good outcomes in the treatment arm were 45% compared to 17% in the medical arm.11
Together, the results of the DAWN and DEFUSE-3 trials significantly expanded the time window in which acute stroke therapy could be offered. In 2018, the AHA/ASA guidelines were revised and supported a Class I level A recommendation for patients presenting in the 6–16 hours time window and class IIA level B-R recommendation for patients presenting in the 16–24 hours time window with baseline good functional status and disabling stroke (NIHSS≥6) due to an anterior circulation proximal occlusion (internal carotid artery, middle cerebral artery segment 1) and tissue at risk (as defined by trial criteria) to undergo stent retriever thrombectomy.37 While the treatment time window studied in trials has been limited to 24 hours, it appears that even patients presenting beyond 24 hours who otherwise meet DAWN criteria may be safely treated with comparable clinical outcomes to those treated within 24 hours.38-40

Treatment Eligibility Based on Current Guidelines

Given the time-sensitive nature of stroke intervention along with the complex infrastructure required to triage, treat and manage large vessel occlusions, the landscape of acute stroke has evolved dramatically with the eventual goal of offering all eligible patients this ground-breaking advancement.12 Paramount to allocating the appropriate resources involves understanding the number of patients that harbor large vessel occlusions and furthermore, how many of those would qualify for class IA treatment. Estimating the frequency of large vessel occlusions is primarily complicated by the definition that is applied as well as the population mix examined. In a recent meta-analysis of 16 studies examining the incidence of large vessel occlusions, the authors identified 9 different classification schemes. The prevalence ranged from 7.3% to 60.6% with a mean prevalence of 31.1% across all studies.41 While all definitions include ICA and MCA-M1 occlusions, there was variable inclusion of basilar occlusions or distal occlusions (MCA-M2, MCA-M3, ACA-A1, ACA-A2, PCA-P1, PCA-P2). Nonetheless, such data provides some estimate for the burden of disease that must now be considered as systems of care are being re-aligned and optimized.
The number of patients eligible for thrombectomy based on current guidelines has been addressed in several studies. In one analysis of 318 patients presenting with acute ischemic stroke over a one-year period, 7% of patients were eligible for EVT based on guideline criteria within the early time window. At a population level, this was estimated to be 11 potential EVT cases per 100,000 person-years.42 A single comprehensive stroke center analysis of 2,667 patients presenting with acute stroke revealed that 2.7% of all patients were EVT eligible based on DAWN or DEFUSE3 criteria.43 Importantly, 42% of all patients presenting in the 6–24 hours time window with anterior circulation large vessel occlusion were EVT eligible.43,44 In a nutshell, 93 in 100 acute ischemic strokes and 1 in 2 acute ischemic strokes with anterior LVO currently do not meet top tier criteria for thrombectomy. Given the disproportionate impact of LVO strokes on morbidity and mortality, thrombectomy should be offered to all eligible patients and reasons for ineligibility must be addressed.
Reasons for treatment ineligibility can be broadly divided into site of occlusion (distal occlusion or posterior circulation occlusion), low NIHSS (<6), large core (ASPECTS <6 or core >70 cc) and poor clinical baseline (mRS >1). In one analysis of 445 patients with large vessel occlusion, reasons for EVT ineligibility included: low NIHSS in 22% of patients, large stroke burden in 21% of patients, poor baseline in 20% of patients, MCA-M2 site of occlusion in 23% of patients and vertebrobasilar site of occlusion in 24% of patients.44 Table 2 provides a concise tabulation of evolution of AHA/ASA guidelines over last 25 years. Certain population subgroups have not been tested in clinical trials and are currently under investigation, hence an analysis of potential need for thrombectomy is required. Based on the study conducted by Desai et al.,44 Table 3 provides approximate estimation of current and projected thrombectomy eligible patients at a comprehensive stroke center in the United States and overall in the United States.
Table 2 AHA/ASA Guidelines
Table 3 Estimated Endovascular Thrombectomy Eligibility per Current and Projected Thrombectomy Eligibility Criteria

Treatment for Medium Vessel Occlusions

Given the efficacy of IV tpa for smaller clot burden and hence more distal occlusions,13 a majority of the EVT trials either under-sampled or excluded MCA-M2 occlusions. An important consideration in this population is the anatomical variability of how much territory the occluded vessel supplies, particularly as it pertains to whether the occlusion is in the proximal or distal MCA-M2 or in a dominant or non-dominant MCA-M2 as well as what topographic regions the MCA-M2 supplies and how many MCA-M2 branches are present. Such heterogeneity has important implications for determining the risk/benefit profile of EVT. Given the paucity of high-quality data, the 2019 AHA/ASA guidelines have issued a class IIB recommendation for EVT in patients with a causative occlusion of the M2 or M3 portion of the MCAs.3 However, numerous single arm studies, non-randomized case-controlled studies and pooled meta-analyses of the EVT trials support the safety and efficacy of EVT for MCA-M2 occlusions.
In a meta-analysis of 12 studies with 1,080 patients undergoing MCA-M2 thrombectomy, good outcomes were noted in 59% of patients with 16% mortality and 10% sICH rates.45 A patient level meta-analysis of the early time window trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, THRACE,9 EXTEND IA, and PISTE) identified 130 patients with MCA-M2 occlusions. A majority were in the proximal location (proximal n = 116 vs distal n = 14). There were higher rates of good outcomes in the EVT group (58.2% vs 39.7%), particularly in those with proximal occlusions.46 The 2019 Society for Neuro-interventional Surgery guidelines have issued a class IA recommendation for thrombectomy in the MCA-M2 location.47 Furthermore, the feasibility of a randomized controlled trial in this population may be limited by lack of clinical equipoise by practitioners.
The issue of occlusions even more distal than the M2 location including the M3 location or occlusions in the anterior and posterior cerebral artery is even less studied. Figure 2 demonstrates a digital subtraction angiogram of 76 years old woman presenting with an acute ischemic stroke (NIHSS score of 9) and harboring a right MCA-M3 occlusion. Several case series have demonstrated the safety and feasibility of clot retrieval in both the anterior and posterior medium sized vessels however the benefit of this approach over the medical arm is poorly understood. With the development of small stent retrievers (“baby” Trevo, Tiger-13), larger size micro-catheters (3 MAX, Headway-27) as well as adjunctive local intra-arterial thrombolytic infusion, there is increasing interest in testing the benefit EVT in this population.
Figure 2 Digital Subtraction Angiography Demonstrating Right MCA-M3 Occlusion

Treatment for Mildly Disabling Strokes

It has long been recognized that while stroke severity is a strong predictor of clinical outcome, a subset of patients with low NIHSS can do poorly with approximately of 30%–35% of patients having poor clinical outcome at 90 days. A majority of patients treated in the EVT trials had an NIHSS of 6 or higher and so there is limited data on this low NIHSS population. In a patient-level pooled analysis of the early time window trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, EXTEND IA), the direction of effect favored EVT for the 177 patients with an NIHSS of 0–10, however the result was not significant and specific results on patients with an NIHSS of 0–5 were not reported.28 Several single center case series have demonstrated the safety and feasibility of EVT for patients with an NIHSS <6, however a recent multi-center study of 251 patients with large vessel occlusion in the setting of a low NIHSS managed with EVT vs medical therapy revealed no significant difference between the 2 groups.48 Likely the low NIHSS population is a heterogeneous group in which additional testing may be necessary to identify the higher risk population. Parameters such as elevated blood pressures, position dependent clinical stability, large perfusion deficit, and presence of motor or language symptoms may help identify the particularly vulnerable population. The benefit of EVT vs medical therapy will be investigated in the ENDO-LOW52 and MOSTE trials.53

Treatment for Large Core Patients

Similar to stroke severity on presentation, infarct burden is a strong predictor of clinical outcomes in the acute ischemic stroke. Early data suggested that at a threshold of 70 cc,54 there was no benefit appreciated after EVT and a majority of the trials set an upper threshold of 50–70cc or ASPECTS of 6. In a patient level meta-analysis of the early time window trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, THRACE, EXTEND IA, and PISTE), benefit after EVT was appreciated in patients with an ASPECTS of 6–10 as well as ASPECTS of 3–5 but not in patients with an ASPECTS of 0–2.28,55 Sample size was small in the low ASPECTS groups but importantly no signal of harm was noted in the large core populations. However, risks of reperfusion injury following recanalization of large stroke are important and several studies identify an increased incidence of post thrombectomy parenchymal hemorrhage amongst large burden strokes. Figure 3 demonstrates a non-contrast CT head-based ASPECTS score of 4 for a 56 years old woman presenting as an acute ischemic stroke with a NIHSS score of 24, time from stroke onset approximately 3 hours, and occlusion of the left internal carotid artery. Multiple additional retrospective and prospective studies of non-randomized have similarly confirmed the safety and feasibility of treating patients with large baseline infarct. The benefit of EVT is likely higher in younger patients, who are able to achieve functional recovery at larger infarct thresholds. The benefit of EVT vs medical therapy, amongst patients with large baseline infarct core and presence of substantial mismatch, will be investigated in the TENSION,56 TESLA57 and LASTE53 trials. Figure 4 demonstrates a CT perfusion map of an acute ischemic stroke patient harboring an acute left MCA-M1 occlusion with a NIHSS score of 22 and time from last known well of 6 hours. Baseline infarct volume is 101 mL (CBF <30%) and Tmax >6 seconds volume is 157 mL.
Figure 3 Non-contrast CT Head Showing ASPECTS Score of 4 in a Stroke Patient With a Left Carotid Artery Occlusion
Figure 4 CT Perfusion Imaging of a Patient With Large Vessel Occlusion With Large Baseline Core Volume (101 mL) and Presence of Substantial Mismatch (Tmax >6 Seconds Volume- 157 mL)

Treatment in Advanced Age and Poor Baseline Patients

While advanced age is a treatment effect modifier for outcomes after acute ischemic stroke, age per se is not considered a contra-indication for EVT. In multiple trials (MR CLEAN, EXTEND-IA, ESCAPE, DEFUSE-3), there was no upper age cutoff for trial inclusion. In a patient level meta-analysis of the early time window trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, THRACE, EXTEND IA, and PISTE58) of outcomes by age, the adjusted treatment effect was highest in patients with age 80 and higher. This likely reflects the particularly poor natural history of untreated large vessel occlusion in the advanced age population. A single center study of 30 nonagenarians undergoing thrombectomy demonstrated that a final infarct volume of <10 cc is a strong predictor of “return to home.”59
While age per se should not be considered a contra-indication for EVT, patients with poor baseline functional status and cognitive impairment were categorically excluded from all the EVT trials. Registry or single center studies of patients with pre-stroke disability have demonstrated that 20%–27% of patients will return to their baseline disability.60 Depending on individual patient and patient family preferences, treatment in these populations may be considered outside of guideline criteria.

Special Populations

Although numerous trials have now demonstrated the benefit of EVT across numerous sub-groups, a majority of the trials excluded patients based on features related to demographics (age <18, pregnant), features that may compromise life expectancy (active cancer) or features that may increase the procedural risks (history of aortic dissection, intra-cranial aneurysm, endocarditis, thrombocytopenia, coagulopathy or underlying non-atherosclerotic vasculopathy). Multiple case series have demonstrated the safety and feasibility of EVT in these populations61-63 however efficacy will be difficult to demonstrate in the setting of a high quality randomized controlled trial given the rarity of these populations. This challenge highlights the importance of maintaining prospective multicenter registries of both treated and untreated large vessel occlusions irrespective of treatment eligibility.

Conclusion

Acute ischemic stroke care has evolved dramatically as this year marks the 26th anniversary of the NINDS tpa trial and the 6th anniversary of the early time window trials. While the general concept of flow restoration is intuitive, the generation of high-quality data proving the benefit of IV therapy and subsequently EVT has been less straight forward and has required attention to appropriate patient selection, rapid work flow and effective treatments. High quality science ultimately informs societal guidelines and tilts organizations and policies to appropriate resources to maximize treatment opportunities. In the absence of high-quality data, treatments will continue to be offered off-label with provider and institutional variability. Irrespective of practice patterns, it is critical to maintain prospective registries and enroll patients in high quality clinical trials when possible.

Appendix Authors

References

1.
National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995; 333(24): 1581-1587.
2.
Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008; 359(13): 1317-1329.
3.
Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American heart association/American stroke association. Stroke. 2019; 50(12): e344-418.
4.
Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015; 372(24): 2296-2306.
5.
Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015; 372(11): 1019-1030.
6.
Campbell BCV, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015; 372(11): 1009-1018.
7.
Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015; 372(24): 2285-2295.
8.
Berkhemer OA, Fransen PSS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015; 372(1): 11-20.
9.
Bracard S, Ducrocq X, Mas JL, et al. Mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke (THRACE): a randomised controlled trial. Lancet Neurol. 2016; 15(11): 1138-1147.
10.
Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018; 378(1): 11-21.
11.
Albers GW, Marks MP, Kemp S, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med. 2018; 378(8): 708-718.
12.
Sacks D, Baxter B, Campbell BCV, et al. Multisociety consensus quality improvement revised consensus statement for endovascular therapy of acute ischemic stroke: from the American Association of Neurological Surgeons (AANS), American Society of Neuroradiology (ASNR), Cardiovascular and Interventional Radiology Society of Europe (CIRSE), Canadian Interventional Radiology Association (CIRA), Congress of Neurological Surgeons (CNS), European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), European Stroke Organization (ESO), Society for Cardiovascular Angiography and Interventions (SCAI), Society of Interventional Radiology (SIR), Society of NeuroInterventional Surgery (SNIS), and World stroke organization (WSO). J Vasc Interv Radiol JVIR. 2018; 29(4): 441-453.
13.
Bhatia R, Hill MD, Nandavar S, et al. Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke. Stroke. 2010; 41(10): 2254-2258.
14.
del Zoppo GJ, Higashida RT, Furlan AJ, Pessin MS, Rowley HA, Gent M. PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. PROACT Investigators. Prolyse in Acute Cerebral Thromboembolism. Stroke. 1998; 29(1): 4-11.
15.
Furlan A, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA. 1999; 282(21): 2003-2011.
16.
Adams HP, Brott TG, Crowell RM, et al. Guidelines for the management of patients with acute ischemic stroke. A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke. 1994; 25(9): 1901-1914.
17.
Adams Harold P, Adams Robert J, Thomas Brott, et al. Guidelines for the early management of patients with ischemic stroke. Stroke. 2003; 34(4): 1056-1083.
18.
Ogawa A, Mori E, Kazuo M, et al. Randomized trial of intraarterial infusion of urokinase within 6 hours of middle cerebral artery stroke. Stroke. 2007; 38(10): 2633-2639.
19.
Smith WS, Sung G, Starkman S, et al. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke. 2005; 36(7): 1432-1438.
20.
Penumbra Pivotal Stroke Trial Investigators. The penumbra pivotal stroke trial: safety and effectiveness of a new generation of mechanical devices for clot removal in intracranial large vessel occlusive disease. Stroke. 2009; 40(8): 2761-2768.
21.
Jauch EC, Saver JL, Adams HP, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013; 44(3): 870-947.
22.
Broderick JP, Palesch YY, Demchuk AM, et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013; 368(10): 893-903.
23.
Ciccone A, Valvassori L, Nichelatti M, et al. Endovascular treatment for acute ischemic stroke. N Engl J Med. 2013; 368(10): 904-913.
24.
Kidwell CS, Jahan R, Gornbein J, et al. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med. 2013; 368(10): 914-923.
25.
Saver JL, Jahan R, Levy EI, et al. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet. 2012; 380(9849): 1241-1249.
26.
Nogueira RG, Lutsep HL, Gupta R, et al. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet. 2012; 380(9849): 1231-1240.
27.
Powers WJ, Derdeyn CP,9 Biller J, et al. 2015 American Heart Association/American Stroke Association focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015; 46(10): 3020-3035.
28.
Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016; 387: 1723-1731.
29.
Ribo M, Molina CA, Cobo E, et al. Association between time to reperfusion and outcome is primarily driven by the time from imaging to reperfusion. Stroke. 2016; 47: 999-1004.
30.
Bhole R, Goyal N, Nearing K, et al. Implications of limiting mechanical thrombectomy to patients with emergent large vessel occlusion meeting top tier evidence criteria. J Neurointerv Surg. 2017; 9(3): 225-228.
31.
Rocha M, Desai SM, Jadhav AP, Jovin TG. Distribution and incidence of fast versus slow progressors of infarct growth in large vessel occlusion stroke. ISC. 2018;38.
32.
Desai SM, Rocha M, Jovin TG, Jadhav AP. High variability in neuronal loss. Stroke. 2019; 50: 34-37.
33.
Dávalos A, Blanco M, Pedraza S, et al. The clinical-DWI mismatch: a new diagnostic approach to the brain tissue at risk of infarction. Neurology. 2004; 62(12): 2187-2192.
34.
Jovin TG, Liebeskind DS, Gupta R, et al. Imaging-based endovascular therapy for acute ischemic stroke due to proximal intracranial anterior circulation occlusion treated beyond 8 hours from time last seen well. Stroke. 2011;42(8): 2206-2211.
35.
Jovin TG, Saver JL, Ribo M, et al. Diffusion-weighted imaging or computerized tomography perfusion assessment with clinical mismatch in the triage of wake up and late presenting strokes undergoing neurointervention with Trevo (DAWN) trial methods. Int J Stroke. 2017; 12(6): 641-652.
36.
Lansberg MG, Straka M, Kemp S, et al. MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study. Lancet Neurol. 2012; 11(10): 860-867.
37.
Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018; 49(3): e46–e110.
38.
Desai SM, Haussen DC, Aghaebrahim A, et al. Thrombectomy 24 hours after stroke: beyond DAWN. J Neurointerv Surg. 2018; 10(11): 1039-1042.
39.
Christensen S, Mlynash M, Kemp S, et al. Persistent target mismatch profile >24 hours after stroke onset in DEFUSE 3. Stroke. 2019; 50(3): 754-757.
40.
Aguilar-Salinas P, Santos R, Granja MF, et al. Revisiting the therapeutic time window dogma: successful thrombectomy 6 days after stroke onset. BMJ Case Rep. 2018;2018:19.
41.
Lakomkin N, Dhamoon M, Carroll K, et al. Prevalence of large vessel occlusion in patients presenting with acute ischemic stroke: a 10-year systematic review of the literature. J Neurointerv Surg. 2019; 11(3): 241-245.
42.
Chia Nicholas H, Leyden James M, Jonathan N, et al., Determining the number of ischemic strokes potentially eligible for endovascular thrombectomy. Stroke. 2016; 47(5): 1377-1380.
43.
Jadhav AP, Desai SM, Kenmuir CL, et al. Eligibility for endovascular trial enrollment in the 6- to 24-hour time window. Stroke. 2018; 49(4):1015-1017.
44.
Desai SM, Starr M, Molyneaux BJ, Rocha M, Jovin TG, Jadhav AP. Acute ischemic stroke with vessel occlusion-prevalence and thrombectomy eligibility at a comprehensive stroke center. J Stroke Cerebrovasc Dis. 2019; 28(11): 104315.
45.
Saber H, Narayanan S, Palla M, et al. Mechanical thrombectomy for acute ischemic stroke with occlusion of the M2 segment of the middle cerebral artery: a meta-analysis. J Neurointerv Surg. 2018; 10(7): 620-624.
46.
Menon BK, Hill MD, Davalos A, et al. Efficacy of endovascular thrombectomy in patients with M2 segment middle cerebral artery occlusions: meta-analysis of data from the HERMES Collaboration. J Neurointerv Surg. 2019; 11(11): 1065-1069.
47.
Mokin M, Ansari SA, McTaggart RA, et al. Indications for thrombectomy in acute ischemic stroke from emergent large vessel occlusion (ELVO): report of the SNIS Standards and Guidelines Committee. J Neurointerv Surg. 2019; 11(3): 215-220.
48.
Goyal N, Tsivgoulis G, Malhotra K, et al. Medical management vs mechanical thrombectomy for mild strokes: an international multicenter study and systematic review and meta-analysis. JAMA Neurol. 2019; 77(1): 16-24.
49.
Adams HP Jr, Brott TG, Furlan AJ, et al. Guidelines for thrombolytic therapy for acute stroke: a supplement to the guidelines for the management of patients with acute ischemic stroke. A statement for healthcare professionals from a Special Writing Group of the Stroke Council, American Heart Association. Circulation. 1996;94(5):1167-1174.
50.
Adams H, Adams R, Del Zoppo G, Goldstein LB; Stroke Council of the American Heart Association; American Stroke Association. Guidelines for the early management of patients with ischemic stroke: 2005 guidelines update a scientific statement from the Stroke Council of the American Heart Association/American Stroke Association. Stroke. 2005;36(4):916-923.
51.
Adams HP Jr, del Zoppo G, Alberts MJ, et al; American Heart Association/American Stroke Association Stroke Council; American Heart Association/American Stroke Association Clinical Cardiology Council; American Heart Association/American Stroke Association Cardiovascular Radiology and Intervention Council; Atherosclerotic Peripheral Vascular Disease Working Group; Quality of Care Outcomes in Research Interdisciplinary Working Group. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation. 2007;115(20):e478-534.
52.
Endovascular Therapy for Low NIHSS Ischemic Strokes - Full Text View - ClinicalTrials.gov. Accessed January 15, 2020. clinicaltrials.gov/ct2/show/NCT04167527.
53.
MOSTE LASTE | In Extremis Study - MOSTE LASTE. MOSTE LASTE Extrem. Study - MOSTE LASTE. Accessed November 24, 2018. inextremis-study.com.
54.
Yoo AJ, Verduzco LA, Schaefer PW, Hirsch JA, Rabinov JD, González RG. MRI-based selection for intra-arterial stroke therapy: value of pretreatment diffusion-weighted imaging lesion volume in selecting patients with acute stroke who will benefit from early recanalization. Stroke. 2009; 40(6): 2046-2054.
55.
Román LS, Menon BK, Blasco J, et al. Imaging features and safety and efficacy of endovascular stroke treatment: a meta-analysis of individual patient-level data. Lancet Neurol. 2018; 17(10): 895-904.
56.
Efficacy and Safety of Thrombectomy in Stroke With Extended Lesion and Extended Time Window - Full Text View - ClinicalTrials.gov. Accessed November 24, 2018. clinicaltrials.gov/ct2/show/NCT03094715.
57.
The TESLA Trial: Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke - Full Text View - ClinicalTrials.gov. Accessed January 15, 2020. clinicaltrials.gov/ct2/show/NCT03805308.
58.
Muir KW, Ford GA, Messow C-M, et al. Endovascular therapy for acute ischaemic stroke: the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) randomised, controlled trial. J Neurol Neurosurg Psychiatry. 2017; 88(1): 38-44.
59.
Tonetti DA, Gross BA, Desai SM, Jadhav AP, Jankowitz BT, Jovin TG. Final infarct volume of <10 cm3 is a strong predictor of return to home in nonagenarians undergoing mechanical thrombectomy. World Neurosurg. 2018; 119: e941-6.
60.
Goldhoorn Robert-Jan B, Merel Verhagen, Dippel Diederik WJ, et al. Safety and outcome of endovascular treatment in prestroke-dependent patients. Stroke. 2018; 49(10): 2406-2414.
61.
Desai SM, Mehta A, Morrison AA, et al. Endovascular thrombectomy, platelet count, and intracranial hemorrhage. World Neurosurg. 2019; 127: e1039-43.
62.
Lee D, Lee DH, Suh DC, et al. Intra-arterial thrombectomy for acute ischaemic stroke patients with active cancer. J Neurol. 2019; 266(9): 2286-2293.
63.
Limaye K, Van de Walle Jones A, Shaban A, et al. Endovascular management of acute large vessel occlusion stroke in pregnancy is safe and feasible. J Neurointerv Surg. 2020; 12(6): 552-556.

Information & Authors

Information

Published In

Neurology®
Volume 97Number 20_Supplement_2November 16, 2021
Pages: S126-S136
PubMed: 34785611

Publication History

Received: May 21, 2020
Accepted: March 5, 2021
Published online: November 16, 2021
Published in print: November 16, 2021

Permissions

Request permissions for this article.

Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Study Funding

No targeted funding reported.

Authors

Affiliations & Disclosures

Ashutosh P. Jadhav, MD, PhD https://orcid.org/0000-0002-9454-0678
From the Department of Neurosurgery (A.P.J.), Barrow Neurological Institute, Phoenix, AZ; HonorHealth Research Institute (S.M.D.), Scottsdale, AZ; and Cooper Neurologic Institute (T.G.J.), Camden, NJ.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Shashvat M. Desai, MD
From the Department of Neurosurgery (A.P.J.), Barrow Neurological Institute, Phoenix, AZ; HonorHealth Research Institute (S.M.D.), Scottsdale, AZ; and Cooper Neurologic Institute (T.G.J.), Camden, NJ.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
From the Department of Neurosurgery (A.P.J.), Barrow Neurological Institute, Phoenix, AZ; HonorHealth Research Institute (S.M.D.), Scottsdale, AZ; and Cooper Neurologic Institute (T.G.J.), Camden, NJ.
Disclosure
Scientific Advisory Boards:
1.
(1) Cerenovus; Commercial; Modest (2) Contego Medical; Commercial; Modest
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1) Stryker Neurovascular; Grant (2) Medtronic; Grant
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
1. Anaconda 2. Blockade Medical 3. Route 92 4. Corindus 5. FreeOx Biotech 6. Viz.ia 7. Methinks
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence Dr. Jadhav [email protected]
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Metrics & Citations

Metrics

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By
  1. Effects of a step-by-step inpatient rehabilitation program on self-care ability and quality of life in patients with acute cerebral infarction following intravascular stent implantation: a prospective cohort study, Frontiers in Neurology, 15, (2024).https://doi.org/10.3389/fneur.2024.1400437
    Crossref
  2. The prognostic value of ASPECTS in specific regions following mechanical thrombectomy in patients with acute ischemic stroke from large-vessel occlusion, Frontiers in Neurology, 15, (2024).https://doi.org/10.3389/fneur.2024.1372778
    Crossref
  3. The evolution of acute stroke care in Germany from 2019 to 2021: analysis of nation-wide administrative datasets, Neurological Research and Practice, 6, 1, (2024).https://doi.org/10.1186/s42466-023-00297-x
    Crossref
  4. Relationship between thrombus vWF and NETs with clinical severity and peripheral blood immunocytes’ indicators in patients with acute ischemic stroke, Interventional Neuroradiology, (2024).https://doi.org/10.1177/15910199241258374
    Crossref
  5. Mechanical thrombectomy for the treatment of large vessel occlusion due to cancer-related cerebral embolism: A systematic review, Interventional Neuroradiology, (2024).https://doi.org/10.1177/15910199241230356
    Crossref
  6. Mechanical thrombectomy for middle cerebral artery M2 occlusions, Acta Radiologica, 65, 6, (663-669), (2024).https://doi.org/10.1177/02841851241248096
    Crossref
  7. Connecting the DOTs: a novel imaging sign on flat-panel detector CT indicating distal vessel occlusions after thrombectomy, Journal of NeuroInterventional Surgery, (jnis-2023-021218), (2024).https://doi.org/10.1136/jnis-2023-021218
    Crossref
  8. A Study of Efficacy and Outcomes of Two Techniques of Mechanical Thrombectomy in Acute Ischemic Stroke, Indian Journal of Neurosurgery, (2024).https://doi.org/10.1055/s-0043-1778689
    Crossref
  9. Dual-Modality Nanoprobe for Noninvasive Detection of Microthrombus after Cerebral Ischemia/Reperfusion, ACS Applied Nano Materials, 7, 1, (292-305), (2024).https://doi.org/10.1021/acsanm.3c04459
    Crossref
  10. Proceedings of the “International Congress on Structural Epilepsy & Symptomatic Seizures” (STESS, Gothenburg, Sweden, 29–31 March 2023), Epilepsy & Behavior, 150, (109538), (2024).https://doi.org/10.1016/j.yebeh.2023.109538
    Crossref
  11. See more
Loading...

View Options

View options

Full Text

View Full Text

Get Access

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login
Purchase Options

The neurology.org payment platform is currently offline. Our technical team is working as quickly as possible to restore service.

If you need immediate support or to place an order, please call or email customer service:

  • 1-800-638-3030 for U.S. customers - 8:30 - 7 pm ET (M-F)
  • 1-301-223-2300 for customers outside the U.S. - 8:30 - 7 pm ET (M-F)
  • [email protected]

We appreciate your patience during this time and apologize for any inconvenience.

Media

Figures

Other

Tables

Share

Share

Share article link

Share