Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke.

BACKGROUND: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well. METHODS: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT. RESULTS: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P<0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P=0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P=0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P=0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P=0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well. CONCLUSIONS: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

Endovascular vs Medical Management for Late Anterior Large Vessel Occlusion With Prestroke Disability: Analysis of CLEAR and RESCUE-Japan.

BACKGROUND AND OBJECTIVES: Current guidelines do not address recommendations for mechanical thrombectomy (MT) in the extended time window (>6 hours after time last seen well [TLSW]) for large vessel occlusion (LVO) patients with preexisting modified Rankin Scale (mRS) > 1. In this study, we evaluated the outcomes of MT vs medical management in patients with prestroke disability presenting in the 6- to 24-hour time window with acute LVO. METHODS: We analyzed a multinational cohort (61 sites, 6 countries from 2014 to 2020) of patients with prestroke (or baseline) mRS 2 to 4 and anterior circulation LVO treated 6-24 hours from TLSW. Patients treated in the extended time window with MT vs medical management were compared using multivariable logistic regression and inverse probability of treatment weighting (IPTW). The primary outcome was the return of Rankin (ROR, return to prestroke mRS by 90 days). RESULTS: Of 554 included patients (448 who underwent MT), the median age was 82 years (interquartile range [IQR] 72-87) and the National Institutes of Health Stroke Scale (NIHSS) was 18 (IQR 13-22). In both MV logistic regression and IPTW analysis, MT was associated with higher odds of ROR (adjusted OR [aOR] 3.96, 95% CI 1.78-8.79 and OR 3.10, 95% CI 1.20-7.98, respectively). Among other factors, premorbid mRS 4 was associated with higher odds of ROR (aOR, 3.68, 95% CI 1.97-6.87), while increasing NIHSS (aOR 0.90, 95% CI 0.86-0.94) and decreasing Alberta Stroke Program Early Computed Tomography Scale score (aOR per point 0.86, 95% CI 0.75-0.99) were associated with lower odds of ROR. Age, intravenous thrombolysis, and occlusion location were not associated with ROR. DISCUSSION: In patients with preexisting disability presenting in the 6- to 24-hour time window, MT is associated with a higher probability of returning to baseline function compared with medical management. CLASSIFICATION OF EVIDENCE: This investigation's results provide Class III evidence that in patients with preexisting disability presenting 6-24 hours from the TLSW and acute anterior LVO stroke, there may be a benefit of MT over medical management in returning to baseline function.

Reperfusion Without Functional Independence in Late Presentation of Stroke With Large Vessel Occlusion.

BACKGROUND: Reperfusion without functional independence (RFI) is an undesired outcome following thrombectomy in acute ischemic stroke. The primary objective was to evaluate, in patients presenting with proximal anterior circulation occlusion stroke in the extended time window, whether selection with computed tomography (CT) perfusion or magnetic resonance imaging is associated with RFI, mortality, or symptomatic intracranial hemorrhage (sICH) compared with noncontrast CT selected patients. METHODS: The CLEAR study (CT for Late Endovascular Reperfusion) was a multicenter, retrospective cohort study of stroke patients undergoing thrombectomy in the extended time window. Inclusion criteria for this analysis were baseline National Institutes of Health Stroke Scale score ≥6, internal carotid artery, M1 or M2 segment occlusion, prestroke modified Rankin Scale score of 0 to 2, time-last-seen-well to treatment 6 to 24 hours, and successful reperfusion (modified Thrombolysis in Cerebral Infarction 2c-3). RESULTS: Of 2304 patients in the CLEAR study, 715 patients met inclusion criteria. Of these, 364 patients (50.9%) showed RFI (ie, mRS score of 3-6 at 90 days despite successful reperfusion), 37 patients (5.2%) suffered sICH, and 127 patients (17.8%) died within 90 days. Neither imaging selection modality for thrombectomy candidacy (noncontrast CT versus CT perfusion versus magnetic resonance imaging) was associated with RFI, sICH, or mortality. Older age, higher baseline National Institutes of Health Stroke Scale, higher prestroke disability, transfer to a comprehensive stroke center, and a longer interval to puncture were associated with RFI. The presence of M2 occlusion and higher baseline Alberta Stroke Program Early CT Score were inversely associated with RFI. Hypertension was associated with sICH. CONCLUSIONS: RFI is a frequent phenomenon in the extended time window. Neither magnetic resonance imaging nor CT perfusion selection for mechanical thrombectomy was associated with RFI, sICH, and mortality compared to noncontrast CT selection alone. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04096248.

Recruitment in a Pragmatic Randomized Trial on the Management of Unruptured Intracranial Aneurysms.

OBJECTIVES: The Comprehensive Aneurysm Management (CAM) study is a pragmatic trial designed to manage unruptured intracranial aneurysm (UIA) patients within a care research framework. METHODS: CAM is an all-inclusive study. Management options are allocated according to an algorithm combining pre-randomization and clinical judgment. Eligible patients are offered 1:1 randomized allocation of intervention versus conservative management and 1:1 randomization allocation of surgical versus endovascular treatment. Ineligible patients are registered. The primary outcome is survival without dependency (modified Rankin Scale score <3) at 10 years. All UIA patients at 1 center are reported. RESULTS: Between February 2020 and July 2021, 403 UIA patients were recruited: 179 (44%) in one of the randomized controlled trials (RCTs) and 224 (56%) in one of the registries. Conservative management was recommended for 205 of 403 patients (51%); of 198 (49%) patients considered for curative treatment, 159 (80%) were randomly allocated conservative (n = 81) or curative treatment (n = 78). These patients were younger and had larger aneurysms than those in the observation registry (P = 0.004). In 39 of 198 patients (20%), conservative management was not considered reasonable (17 patients were recommended endovascular, 2 surgery, and 20 the RCT comparing endovascular with surgical treatment). In total, 70 patients were recruited in the RCT comparing surgery and endovascular treatment. After informed discussion at time of consent, 141 of 159 patients (89%) agreed with the randomly allocated management plan, while 11% crossed over to the alternative management option. CONCLUSIONS: CAM was successfully integrated into routine practice. Meaningful conclusions can be obtained if multiple centers actively participate in the trial.

Pregnancy as a Subgroup in the Pathophysiologic Classification of Spinal Aneurysms.

BACKGROUND: Aneurysms of spinal arteries not associated with any known predisposing condition are referred to as isolated spinal aneurysms (SAs). In our series, an SA was found in 2 patients during the postpartum period. The goal of this study is to determine whether an occurrence of an SA may be related to puerperium. METHODS: In a retrospective analysis of our consecutive series of 10 cases of SAs from 2008 to 2020, we identified 2 cases of SAs during puerperium. Patients' charts and imaging were reviewed, for potential predisposing factors. RESULTS: In both cases, angiography showed fusiform aneurysms of the anterior SA with concomitant bilateral vertebral artery (VA) dissections. Serum vasculitis and inflammatory panel and genetic testing for collagen disorders were negative in both cases. Review of the literature showed that pregnancy is associated with an increased risk of arterial dissections in various locations and supports the hypothesis that hemodynamic and hormonal changes may play a role in the formation of SAs. CONCLUSIONS: Pregnancy and peripartum state may be a distinct cause of the formation of SAs, possibly as a result of increased hemodynamic stress and hormonal changes that may alter the arterial wall. It would be appropriate to add pregnancy as a subgroup in the classification of SAs. In our series, both cases were associated with bilateral VA dissections; it is possible that the bilateral VA stenosis may have contributed to the formation of the SAs. It is important to recognize this possibility when considering the occlusion of a dissected VA.

Noncontrast Computed Tomography vs Computed Tomography Perfusion or Magnetic Resonance Imaging Selection in Late Presentation of Stroke With Large-Vessel Occlusion.

Importance: Advanced imaging for patient selection in mechanical thrombectomy is not widely available. Objective: To compare the clinical outcomes of patients selected for mechanical thrombectomy by noncontrast computed tomography (CT) vs those selected by computed tomography perfusion (CTP) or magnetic resonance imaging (MRI) in the extended time window. Design, Setting, and Participants: This multinational cohort study included consecutive patients with proximal anterior circulation occlusion stroke presenting within 6 to 24 hours of time last seen well from January 2014 to December 2020. This study was conducted at 15 sites across 5 countries in Europe and North America. The duration of follow-up was 90 days from stroke onset. Exposures: Computed tomography with Alberta Stroke Program Early CT Score, CTP, or MRI. Main Outcomes and Measures: The primary end point was the distribution of modified Rankin Scale (mRS) scores at 90 days (ordinal shift). Secondary outcomes included the rates of 90-day functional independence (mRS scores of 0-2), symptomatic intracranial hemorrhage, and 90-day mortality. Results: Of 2304 patients screened for eligibility, 1604 patients were included, with a median (IQR) age of 70 (59-80) years; 848 (52.9%) were women. A total of 534 patients were selected to undergo mechanical thrombectomy by CT, 752 by CTP, and 318 by MRI. After adjustment of confounders, there was no difference in 90-day ordinal mRS shift between patients selected by CT vs CTP (adjusted odds ratio [aOR], 0.95 [95% CI, 0.77-1.17]; P = .64) or CT vs MRI (aOR, 0.95 [95% CI, 0.8-1.13]; P = .55). The rates of 90-day functional independence (mRS scores 0-2 vs 3-6) were similar between patients selected by CT vs CTP (aOR, 0.90 [95% CI, 0.7-1.16]; P = .42) but lower in patients selected by MRI than CT (aOR, 0.79 [95% CI, 0.64-0.98]; P = .03). Successful reperfusion was more common in the CT and CTP groups compared with the MRI group (474 [88.9%] and 670 [89.5%] vs 250 [78.9%]; P < .001). No significant differences in symptomatic intracranial hemorrhage (CT, 42 [8.1%]; CTP, 43 [5.8%]; MRI, 15 [4.7%]; P = .11) or 90-day mortality (CT, 125 [23.4%]; CTP, 159 [21.1%]; MRI, 62 [19.5%]; P = .38) were observed. Conclusions and Relevance: In patients undergoing proximal anterior circulation mechanical thrombectomy in the extended time window, there were no significant differences in the clinical outcomes of patients selected with noncontrast CT compared with those selected with CTP or MRI. These findings have the potential to widen the indication for treating patients in the extended window using a simpler and more widespread noncontrast CT-only paradigm.

Fatal hemorrhagic complication after coil embolization of a petrosal arteriovenous shunt.

BACKGROUND: Cerebello-pontine AVMs (CPAVMs) and petrous apex dural arteriovenous fistulae (DAVFs) are rare and sometimes difficult to distinguish. We report a fatal hemorrhagic complication after coil embolization of the petrosal vein draining a trigeminal AVM misdiagnosed as a DAVF. CASE PRESENTATION: A 73-year-old woman with a petrous apex arteriovenous shunt with dual dural and pial arterial supply presented with posterior fossa hemorrhage. The draining petrosal vein was catheterized and coiled via the superior petrosal sinus. Two episodes of contrast extravasation occurred during coiling, but the lesion was completely occluded at the end of the procedure. The patient developed a fatal posterior fossa hemorrhage in the recovery room. Microscopic pathology revealed numerous dilated vessels within the trigeminal nerve. CONCLUSION: CPAVMs and DAVFs with pial drainage should be distinguished pre-operatively. Occlusion of a pial vein (as opposed to a sinus) in the treatment of an arteriovenous shunt carries hemorrhagic risk if a liquid embolic agent is not used to completely occlude all pathological vessels.

Angiographic results of surgical or endovascular treatment of intracranial aneurysms: a systematic review and inter-observer reliability study.

PURPOSE: Results of surgical or endovascular treatment of intracranial aneurysms are often assessed using angiography. A reliable method to report results irrespective of treatment modality is needed to enable comparisons. Our goals were to systematically review existing classification systems, and to propose a 3-point classification applicable to both treatments and assess its reliability. METHODS: We conducted two systematic reviews on classification systems of angiographic results after clipping or coiling to select a simple 3-category scale that could apply to both treatments. We then circulated an electronic portfolio of angiograms of clipped (n=30) or coiled (n=30) aneurysms, and asked raters to evaluate the degree of occlusion using this scale. Raters were also asked to choose an appropriate follow-up management for each patient based on the degree of occlusion. Agreement was assessed using Krippendorff's α statistics (αK), and relationship between occlusion grade and clinical management was analyzed using Fisher's exact and Cramer's V tests. RESULTS: The systematic reviews found 70 different grading scales with heterogeneous reliability (kappa values from 0.12 to 1.00). The 60-patient portfolio was independently evaluated by 19 raters of diverse backgrounds (neurosurgery, radiology, and neurology) and experience. There was substantial agreement (αK=0.76, 95%CI, 0.67-0.83) between raters, regardless of background, experience, or treatment used. Intra-rater agreement ranged from moderate to almost perfect. A strong relationship was found between angiographic grades and management decisions (Cramer's V: 0.80±0.12). CONCLUSION: A simple 3-point scale demonstrated sufficient reliability to be used in reporting aneurysm treatments or in evaluating treatment results in comparative randomized trials.

Repeated Retching and Vomiting in the Pathophysiology of Isolated Spinal Aneurysms.

BACKGROUND: Rupture of spinal aneurysms is a rare cause of subarachnoid hemorrhage. These aneurysms are often associated with a variety of vascular malformations that increase blood flow in the spinal circulation or with disorders that compromise the vessel wall. However, spinal aneurysms may be isolated, not associated with any known predisposing condition. The objective of this study is to explore the possible mechanisms associated with the formation and rupture of isolated spinal aneurysms (ISAs). METHODS: We conducted a retrospective review of a series of consecutive patients admitted for a ruptured ISA. In all cases, spinal angiography confirmed the presence of a spinal aneurysm responsible for the bleeding. Particular attention was paid to medical history and symptoms before bleeding, for potential factors predisposing to their formation and rupture. RESULTS: Between 2008 and 2020, ten cases of spinal aneurysms were seen at our institution including 4 cases of ISA. All patients with ISA were female, and in 3 cases the aneurysm involved the territory of the posterior spinal artery. In 3 of these 4 (75%) ISA cases, there was a strikingly similar history of retching and vomiting preceding the thunderclap headache. In 1 patient, the aneurysm was surgically resected; pathologic analysis revealed a fusiform dissecting aneurysm. All 4 patients had a favorable outcome. CONCLUSIONS: We suggest that the straining during prolonged retching and vomiting plays a role in the formation and rupture of some ISAs, possibly because of pressure spikes, increased transmural arterial pressure, and increased wall shear stress during straining.

Surgical or Endovascular Management of Middle Cerebral Artery Aneurysms: A Randomized Comparison.

OBJECTIVE: There are few randomized data comparing clipping and coiling for middle cerebral artery (MCA) aneurysms. We analyzed results from patients with MCA aneurysms enrolled in the CURES (Collaborative UnRuptured Endovascular vs. Surgery) and ISAT-2 (International Subarachnoid Aneurysm Trial II) randomized trials. METHODS: Both trials are investigator-led parallel-group 1:1 randomized studies. CURES includes patients with 3-mm to 25-mm unruptured intracranial aneurysms (UIAs), and ISAT-2 includes patients with ruptured aneurysms (RA) for whom uncertainty remains after ISAT. The primary outcome measure of CURES is treatment failure: 1) failure to treat the aneurysm, 2) intracranial hemorrhage during follow-up, or 3) residual aneurysm at 1 year. The primary outcome of ISAT-2 is death or dependency (modified Rankin Scale score >2) at 1 year. One-year angiographic outcomes are systematically recorded. RESULTS: There were 100 unruptured and 71 ruptured MCA aneurysms. In CURES, 90 patients with UIA have been treated and 10 await treatment. Surgical and endovascular management of unruptured MCA aneurysms led to treatment failure in 3/42 (7%; 95% confidence interval [CI], 0.02-0.19) for clipping and 13/48 (27%; 95% CI, 0.17-0.41) for coiling (P = 0.025). All 71 patients with RA have been treated. In ISAT-2, patients with ruptured MCA aneurysms managed surgically had died or were dependent (modified Rankin Scale score >2) in 7/38 (18%; 95% CI, 0.09-0.33) cases, and 8/33 (24%; 95% CI, 0.13-0.41) for endovascular. One-year imaging results were available in 80 patients with UIA and 62 with RA. Complete aneurysm occlusion was found in 30/40 (75%; 95% CI, 0.60-0.86) patients with UIA allocated clipping, and 14/40 (35%; 95% CI, 0.22-0.50) patients with UIA allocated coiling. Complete aneurysm occlusion was found in 24/34 (71%; 95% CI, 0.54-0.83) patients with RA allocated clipping, and 15/28 (54%; 95% CI, 0.36-0.70) patients with RA allocated coiling. CONCLUSIONS: Randomized data from 2 trials show that better efficacy may be obtained with surgical management of patients with MCA aneurysms.

Measuring clinical uncertainty and equipoise by applying the agreement study methodology to patient management decisions.

BACKGROUND: Clinical uncertainty and equipoise are vague notions that play important roles in contemporary problems of medical care and research, including the design and conduct of pragmatic trials. Our goal was to show how the reliability study methods normally used to assess diagnostic tests can be applied to particular management decisions to measure the degree of uncertainty and equipoise regarding the use of rival management options. METHODS: We first use thrombectomy in acute stroke as an illustrative example of the method we propose. We then review, item by item, how the various design elements of diagnostic reliability studies can be modified in order to measure clinical uncertainty. RESULTS: The thrombectomy example shows sufficient disagreement and uncertainty to warrant the conduct of additional randomized trials. The general method we propose is that a sufficient number of diverse individual cases sharing a similar clinical problem and covering a wide spectrum of clinical presentations be assembled into a portfolio that is submitted to a variety of clinicians who routinely manage patients with the clinical problem. DISCUSSION: Clinicians are asked to independently choose one of the predefined management options, which are selected from those that would be compared within a randomized trial that would address the clinical dilemma. Intra-rater agreement can be assessed at a later time with a second evaluation. Various professional judgments concerning individual patients can then be compared and analyzed using kappa statistics or similar methods. Interpretation of results can be facilitated by providing examples or by translating the results into clinically meaningful summary sentences. CONCLUSIONS: Measuring the uncertainty regarding management options for clinical problems may reveal substantial disagreement, provide an empirical foundation for the notion of equipoise, and inform or facilitate the design/conduct of clinical trials to address the clinical dilemma.

Residual Cerebral Aneurysms After Microsurgical Clipping: A New Scale, an Agreement Study, and a Systematic Review of the Literature.

OBJECTIVE: The surgical repair of a cerebral aneurysm does not always lead to complete occlusion. A standardized repeatable method of reporting results of surgical clipping is desirable. Our purpose was to systematically review methods of classifying aneurysm remnants, provide a new scale with precise definitions of categories, and perform an agreement study to assess the variability in adjudicating remnants after aneurysm clipping. METHODS: A systematic review was performed to identify ways to report angiographic results of surgical clipping between 1963 and 2017. Postclipping angiographic results of 43 patients were also independently evaluated by 10 raters of various experience and backgrounds using a new 4-category scale. Agreement between responses were analyzed using κ statistics. RESULTS: The systematic review yielded 63 articles with 37 different nomenclatures using 2-6 categories. The reliability of judging the presence of an aneurysm remnant on catheter angiography was studied only twice, with only 2 raters each time, with contradictory results. Interobserver agreement using the new 4-category scale was moderate (κ = 0.52; 95% confidence interval, 0.43-0.62) for all observers, but improved to substantial (κ = 0.62; 95% confidence interval, 0.47-0.76) when results were dichotomized (grade 0/1 vs. 2/3). CONCLUSIONS: Various classification schemes to evaluate angiographic results after surgical clipping exist in the literature, but they lack standardization. Adjudication using fewer, better defined categories may yield more reliable agreement.

Flow diversion: what can clinicians learn from animal models?

INTRODUCTION: Flow diversion is increasingly used for treating intracranial aneurysms. This article aims to review the evidence obtained from animal models and summarizes the findings that might be of clinical interest. METHODS: From a systematic review of studies published between 2000 and 2016, we extracted the data on the following questions: What roles do aneurysm dimension, morphology, and vascular geometry have on success of flow diversion? What characteristics of a flow diverter can influence aneurysm occlusion? What are the risk factors for jailed branch occlusion? RESULTS: Flow diversion has been shown to be less effective in occluding large aneurysms with wide or undefined necks, as compared to smaller aneurysms with narrower necks. Straight sidewall aneurysms were more likely to occlude after flow diversion than curved sidewall aneurysms or bifurcation aneurysms with branches originating from the neck or the fundus. The main characteristics of devices that may impact on the success of flow diversion are porosity and pore-density, but challenging aneurysm models were not better occluded with devices of lower porosity. Porosity is not uniform when devices deform to adapt to local in vivo anatomy when deployed. Neointima formation on devices correlates with low porosity. Branches are rarely occluded when they are jailed, but persistent branch flow may prevent aneurysm occlusion. CONCLUSION: Experimental models may help anticipate clinical results of flow diversion.

Embolization with larger-caliber coils can increase packing density: Evidence from the pilot phase of a randomized trial.

Background and purpose Endovascular coil embolization of cerebral aneurysms is associated with suboptimal angiographic results in up to 20-30% of patients. Coil packing density has been used as an index of the success of the initial procedure. The trial sought to study the effects of using 15-caliber coils, as compared with 10-caliber coils, on packing density. Methods Does Embolization with Larger coils lead to better Treatment of Aneurysms (DELTA) is an investigator-initiated multicenter prospective, randomized, controlled clinical trial. Patients are randomized 1:1 to embolization with either 10-caliber coils exclusively (control group) or the highest safely achievable proportion of 15-caliber coils and 10-caliber coils if necessary (intervention group) in 4-12-mm aneurysms. The endpoint of the pilot phase of the trial was the capacity to increase packing density of the initial procedure, calculated using a mathematical transformation of the dimensions entered into the case report forms. Secondary outcomes included the total number of coils used per aneurysm, total fluoroscopy time, initial angiographic outcomes and any adverse or undesirable event. Results Seventy patients were recruited between June 2014 and November 2015. Compared with 10-caliber coils, the 15-caliber coil group had a higher median packing density (44% vs 24%, p = 0.017). Results of other outcome measures were similar for the two groups. Conclusion Coiling of small and medium aneurysms randomized to 15-caliber coils achieved higher packing densities compared with coiling using 10-caliber coils.

Early CT changes in patients admitted for thrombectomy: Intrarater and interrater agreement.

OBJECTIVE: To systematically review the literature and assess agreement on the Alberta Stroke Program Early CT Score (ASPECTS) among clinicians involved in the management of thrombectomy candidates. METHODS: Studies assessing agreement using ASPECTS published from 2000 to 2015 were reviewed. Fifteen raters reviewed and scored the anonymized CT scans of 30 patients recruited in a local thrombectomy trial during 2 independent sessions, in order to study intrarater and interrater agreement. Agreement was measured using intraclass correlation coefficients (ICCs) and Fleiss kappa statistics for ASPECTS and dichotomized ASPECTS at various cutoff values. RESULTS: The review yielded 30 articles reporting 40 measures of agreement. Populations, methods, analyses, and results were heterogeneous (slight to excellent agreement), precluding a meta-analysis. When analyzed as a categorical variable, intrarater agreement was slight to moderate (κ = 0.042-0.469); it reached a substantial level (κ > 0.6) in 11/15 raters when the score was dichotomized (0-5 vs 6-10). The interrater ICCs varied between 0.672 and 0.811, but agreement was slight to moderate (κ = 0.129-0.315). Even in the best of cases, when ASPECTS was dichotomized as 0-5 vs 6-10, interrater agreement did not reach a substantial level (κ = 0.561), which translates into at least 5 of 15 raters not giving the same dichotomized verdict in 15% of patients. CONCLUSIONS: In patients considered for thrombectomy, there may be insufficient agreement between clinicians for ASPECTS to be reliably used as a criterion for treatment decisions.