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Background: Individualized clinical decisions are often made by considering some patient or lesion characteristics that are thought to have an impact on the efficacy or safety of treatment. For example, aneurysm size and neck width have often been determinants of treatment choices in neurovascular practice., Methods: We review observational and randomized data on the influence of aneurysm or neck size on angiographic results of coiling, stent-assisted coiling, or surgical clipping. New RCT data are used to demonstrate the shortcomings of managing patients using clinical judgment regarding patient or lesion characteristics. We discuss why clinical decisions should not be based on comparisons of different patients treated by the same treatment. Clinical decision making requires a comparison between the same patients treated with different treatments in a randomized trial., Results: The results of endovascular treatment of large or wide-necked aneurysms are always inferior to those of small or narrow-necked aneurysms, in observational as well as in randomized studies. However, this fact alone is not sufficient to infer that patients with small aneurysms should be coiled, while those with large aneurysms should be managed with stenting or surgical clipping. The purported superiority of clipping for large aneurysms could not be demonstrated in recent RCTs (while surgery was found superior for small aneurysms). Similarly, the superiority of stent-assisted coiling for wide-necked aneurysms was not shown in another recent RCT., Conclusion: Clinical experience and observational studies alone can mislead practice. Proper clinical decisions for individuals requires randomized evidence., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: The scientific role randomization plays in clinical research is universally recognized, but poorly understood. In stark contrast, the ethical role randomization plays in the proper care of patients in the presence of uncertainty has been almost completely ignored., Methods: We review the introduction of randomization in the design of experiments, its first use in Britain, and its essential role in analysis of statistical results. We also review Thomas Chalmers' argument from 1975 that showed the ethical role randomization can play in the care of patients. We discuss how Chalmers' vision can be generalized to all contexts of clinical uncertainty., Discussion: Randomization is not only essential to the validity of statistical tests, it is also the best way to learn from experience. Although Chalmers' admonition to 'Randomize the first patient' pertained to the use of innovations, the notion that randomized allocation can be done in the best interest of patients is generalizable to all medical or surgical interventions that have yet to be proven beneficial, opening the perspective that care research can be integrated into practice in the best medical interest of patients., Conclusion: Randomized allocation plays crucial scientific and ethical roles both in research and practice. It is the most efficient way to learn from experience. Prior to this gain in knowledge, it is the way to optimize care in the presence of uncertainty., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Many randomized trials that aim to assess new or commonly used medical or surgical interventions have been so small that the validity of conclusions becomes questionable., Methods: We illustrate the small trial problem using the power calculation of five Cochrane-reviewed studies that compared vertebroplasty versus placebo interventions. We discuss some of the reasons why the statistical admonition not to dichotomize continuous variables may not apply to the calculation of the number of patients required for trials to be meaningful., Results: Placebo-controlled vertebroplasty trials planned to recruit between 23 and 71 patients per group. Four of five studies used the standardized mean difference of a continuous pain variable (centimeters on the visual analog scale (VAS)) to plan implausibly small trials. What is needed is not a mean effect at the population level but a measure of efficacy at the patient level. Clinical practice concerns the care of individual patients that vary in many more respects than the variation around the mean of a single selected variable. The inference from trial to practice concerns the frequency of success of the experimental intervention performed one patient at a time. A comparison of the proportions of patients reaching a certain threshold is a more meaningful method that appropriately requires larger trials., Conclusion: Most placebo-controlled vertebroplasty trials used comparisons of means of a continuous variable and were consequently very small. Randomized trials should instead be large enough to account for the diversity of future patients and practices. They should offer an evaluation of a clinically meaningful number of interventions performed in various contexts. Implications of this principle are not specific to placebo-controlled surgical trials. Trials designed to inform practice require a per-patient comparison of outcomes and the size of the trial should be planned accordingly., (© 2023. The Author(s).)

Background: The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is an all-inclusive pragmatic study comprising 2 randomized clinical trials (RCTs). Patients excluded from the RCTs are followed in parallel treatment and observation registries, allowing a comparison between RCT and registry patients., Methods: The first randomized clinical trial (RCT-1) offers 1:1 randomized allocation of intervention versus conservative management for patients with arteriovenous malformation (AVM). The second randomized clinical trial (RCT-2) allocates 1:1 pre-embolization or no pre-embolization to surgery or radiosurgery patients judged treatable with or without embolization. Characteristics of RCT patients are reported and compared to registry patients., Results: From June 2014 to May 2021, 1010 patients with AVM were recruited; 498 patients were observed and 373 were included in the treatment registries. Randomized allocation in RCT-1 was applied to 139 (26%) of the 512 patients (including 127 of 222 [57%] with unruptured AVMs) considered for curative treatment. RCT-1 AVM patients differed (in rupture status, Spetzler-Martin grade and baseline modified Rankin Score) from those in the observation or treatment registries (P < 0.001). Most patients had small (<3 cm; 71%) low-grade (Spetzler-Martin I-II; 64%) unruptured (91%) AVMs. The allocated management was conservative (n = 71) or curative (n = 68), using surgery (n = 39), embolization (n = 16), or stereotactic radiosurgery (n = 13). Pre-embolization was considered for 179/309 (58%) patients allocated/assigned to surgery or stereotactic radiosurgery; 87/179 (49%) were included in RCT-2. RCT-2 patient AVMs differed in size, eloquence and grade from patients of the pre-embolization registry (P < 0.01). Most had small (<3 cm in 82%) low-grade (83%) AVMs in non-eloquent brain (64%)., Conclusions: Patients included in the RCTs differ significantly from registry patients. Meaningful results can be obtained if multiple centers actively participate in the TOBAS RCTs., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is a pragmatic study that includes 2 randomized trials and registries of treated or conservatively managed patients. The authors report the results of the surgical registry., Methods: TOBAS patients are managed according to an algorithm that combines clinical judgment and randomized allocation. For patients considered for curative treatment, clinicians selected from surgery, endovascular therapy, or radiation therapy as the primary curative method, and whether observation was a reasonable alternative. When surgery was selected and observation was deemed unreasonable, the patient was not included in the randomized controlled trial but placed in the surgical registry. The primary outcome of the trial was mRS score > 2 at 10 years (at last follow-up for the current report). Secondary outcomes include angiographic results, perioperative serious adverse events, and permanent treatment-related complications leading to mRS score > 2., Results: From June 2014 to May 2021, 1010 patients were recruited at 30 TOBAS centers. Surgery was selected for 229/512 patients (44%) considered for curative treatment; 77 (34%) were included in the surgery versus observation randomized trial and 152 (66%) were placed in the surgical registry. Surgical registry patients had 124/152 (82%) ruptured and 28/152 (18%) unruptured arteriovenous malformations (AVMs), with the majority categorized as low-grade Spetzler-Martin grade I-II AVM (118/152 [78%]). Thirteen patients were excluded, leaving 139 patients for analysis. Embolization was performed prior to surgery in 78/139 (56%) patients. Surgical angiographic cure was obtained in 123/139 all-grade (89%, 95% CI 82%-93%) and 105/110 low-grade (95%, 95% CI 90%-98%) AVM patients. At the mean follow-up of 18.1 months, 16 patients (12%, 95% CI 7%-18%) had reached the primary safety outcome of mRS score > 2, including 11/16 who had a baseline mRS score ≥ 3 due to previous AVM rupture. Serious adverse events occurred in 29 patients (21%, 95% CI 15%-28%). Permanent treatment-related complications leading to mRS score > 2 occurred in 6/139 patients (4%, 95% CI 2%-9%), 5 (83%) of whom had complications due to preoperative embolization., Conclusions: The surgical treatment of brain AVMs in the TOBAS registry was curative in 88% of patients. The participation of more patients, surgeons, and centers in randomized trials is needed to definitively establish the role of surgery in the treatment of unruptured brain AVMs. Clinical trial registration no.: NCT02098252 (ClinicalTrials.gov).

Background: Whether the best management of middle cerebral artery (MCA) aneurysm patients is surgical or endovascular remains uncertain, with little evidence to guide decision-making. A randomized care trial offering MCA aneurysm patients a 50% chance of surgical and a 50% chance of endovascular management may optimize outcomes in the presence of uncertainty., Methods: The Middle Cerebral Artery Aneurysm Trial (MCAAT) is an investigator-initiated, multicenter, parallel group, prospective, 1:1 randomized controlled clinical trial. All adult patients with MCA aneurysms, ruptured or unruptured, amenable to surgical and endovascular treatment can be included. The composite primary outcome is "Treatment Success": (i) occlusion or exclusion of the aneurysm using the allocated treatment modality; (ii) no intracranial hemorrhage during follow-up; (iii) no retreatment of the target aneurysm during follow-up, (iv) no residual aneurysm on angiographic follow-up; and (v) independence (mRS <3) at 1 year. The trial tests 2 versions of the same hypothesis (one for ruptured and one for unruptured MCA aneurysm patients): Surgical management will lead to a 15% absolute increase in the proportion of patients reaching Treatment Success from 55% to 70% (ruptured) or from 75% to 90% (unruptured aneurysm patients) compared with endovascular treatment (any method). In this pragmatic trial, outcome evaluations are by treating physicians, except for 1-year angiographic results which will be core lab assessed. The trial will be monitored by an independent data safety monitoring committee to assure safety of participants. MCAAT is registered at clinicaltrials.gov: NCT05161377., Conclusions: Patients with MCA aneurysms can be optimally managed within a care trial protocol., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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 (α K ), 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 (α K =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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The current research-care separation was introduced to protect patients from explanatory studies designed to gain knowledge for future patients. Care trials are all-inclusive pragmatic trials integrated into medical practice, with no extra tests, risks, or cost, and have been designed to guide practice under uncertainty in the best medical interest of the patient., Proposed Revision: Patients need a distinction between validated care, previously verified to provide better outcomes, and promising but unvalidated care, which may include unnecessary or even harmful interventions. While validated care can be practiced normally, unvalidated care should only be offered within declared pragmatic care research, designed to protect patients from harm. The validated/unvalidated care distinction is normative, necessary to the ethics of medical practice. Care trials, which mark the distinction and allow the tentative use of promising interventions necessarily involve patients, and thus the design and conduct of pragmatic care research must respect the overarching rule of care ethics "to always act in the best medical interest of the patient." Yet, unvalidated interventions offered in contexts of medical uncertainty cannot be prescribed or practiced as if they were validated care. The medical interests of current patients are best protected when unvalidated practices are restricted to a care trial protocol, with 1:1 random allocation (or "hemi-prescription") versus previously validated care, to optimize potential benefits and minimize risks for each patient., Conclusion: Pragmatic trials can regulate medical practice by providing (i) a transparent demarcation between unvalidated and validated care; (ii) norms of medical conduct when using tests and interventions of yet unknown benefits in practice; and eventually (iii) a verdict regarding optimal care.

Background: A sustained release microparticle formulation of nimodipine (EG-1962) was developed for treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH)., Objective: To assess safety, tolerability, and pharmacokinetics of intracisternal EG-1962 in an open-label, randomized, phase 2 study of up to 12 subjects., Methods: Subjects were World Federation of Neurological Surgeons grades 1 to 2, modified Fisher grades 2 to 4, and underwent aneurysm clipping within 48 h of aSAH. EG-1962, containing 600 mg nimodipine, was administered into the basal cisterns. Outcome on the extended Glasgow Outcome Scale (eGOS), pharmacokinetics, delayed cerebral ischemia and infarction, rescue therapy, and safety were evaluated., Results: The study was halted when a phase 3 study of intraventricular EG-1962 stopped because that study was unlikely to meet its primary endpoint. Six subjects were randomized (5 EG-1962 and 1 oral nimodipine). After 90-d follow-up, favorable outcome on the eGOS occurred in 1 of 5 EG-1962 and in the single oral nimodipine patient. Four EG-1962 and the oral nimodipine subject had angiographic vasospasm. One EG-1962 subject had delayed cerebral ischemia, and all subjects with angiographic vasospasm received rescue therapy except 1 EG-1962 patient. One subject treated with EG-1962 developed right internal carotid and middle cerebral artery narrowing 5 mo after placement of EG-1962, leading to occlusion and cerebral infarction. Pharmacokinetics showed similar plasma concentrations of nimodipine in both groups., Conclusion: Angiographic vasospasm and unfavorable clinical outcome still occurred after placement of EG-1962. Internal carotid artery narrowing and occlusion after placement of EG-1962 in the basal cisterns has not been reported., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Background: In the absence of randomized evidence, the optimal management of patients with unruptured intracranial aneurysms (UIA) remains uncertain., Methods: Comprehensive Aneurysm Management (CAM) is an all-inclusive care trial combined with a registry. Any patient with a UIA (no history of intracranial hemorrhage within the previous 30 days) can be recruited, and treatment allocation will follow an algorithm combining clinical judgment and randomization. Patients eligible for at least 2 management options will be randomly allocated 1:1 to conservative or curative treatment. Minimization will be used to balance risk factors, using aneurysm size (≥7 mm), location (anterior or posterior circulation), and age <60 years., Results: The CAM primary outcome is survival without neurologic dependency (modified Rankin Scale [mRS] score <3) at 10 years. Secondary outcome measures include the incidence of subarachnoid hemorrhage during follow-up and related morbidity and mortality; morbidity and mortality related to endovascular treatment or surgical treatment of the UIA at 1 year; overall morbidity and mortality at 1, 5, and 10 years; when relevant, duration of hospitalization; and, when relevant, discharge to a location other than home. The primary hypothesis for patients randomly allocated to at least 2 options, 1 of which is conservative management, is that active UIA treatment will reduce the 10-year combined neurologic morbidity and mortality (mRS score >2) from 24% to 16%. At least 961 patients recruited from at least 20 centers over 4 years will be needed for the randomized portion of the study., Conclusions: Patients with unruptured intracranial aneurysms can be comprehensively managed within the context of an all-inclusive care trial., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

Background: Posterior fossa arteriovenous malformations (pfAVMs) can be challenging lesions to manage. AVMs in this location may have distinct features compared with supratentorial AVMs. Our aim was to systematically review the literature on the presenting characteristics of pfAVMs and compare clinical and angiographic outcomes after the various types of treatment employed., Methods: The review was conducted according to the Cochrane Collaboration guidelines. Electronic databases from 1900 to March 2018 were searched and complemented by hand-searching and cross-referencing. Articles were categorized into (i) AVM studies that included those in the posterior fossa, (ii) those that focused exclusively on pfAVM, and (iii) those that further specified a cerebellar or brainstem location of the AVM., Results: Seventy-seven articles with 4512 pfAVM patients were retained for analyses. Compared with historical supratentorial controls, pfAVMs were reported to more frequently present with rupture, to more commonly have associated arterial aneurysms, and to more frequently lead to poor clinical and angiographic outcomes. The quality of the literature and lack of standardization of outcome reporting precluded performing a meta-analysis on the results of the various different treatment modalities., Conclusions: Posterior fossa AVMs may have some distinct features compared with supratentorial AVMs. The available reports on pfAVMs are not sufficiently standardized to provide reliable guidance for patient management decisions. This goal will require future studies to be multicentric and to focus on standardized, repeatable clinical and angiographic outcomes.

Background: Randomized trials of commonly performed surgical interventions are notoriously difficult to conduct. The trial methodology may nevertheless be the best way to offer outcome-based neurovascular care in the presence of uncertainty. One obstacle to promoting such trials is the conventional prohibition of publication and dissemination of interim results as the trial progresses., Methods: We review the scientific and statistical reasons against the publication of interim analyses as well as exceptions that can occur when 1 treatment is unexpectedly shown to be harmful or when the results of other trials have convincingly shown the comparative benefits of a new intervention. We also discuss the promotion of difficult surgical trials., Results: Reasons to support the conventional ban on publication of interim results include control of statistical errors, prevention of invalid conclusions, and dissemination of false claims of equivalence of rival interventions. In the early phases of a trial, usually 1 treatment cannot be shown superior to the other. We believe, contrary to the received view, that a transparent report of the early progress of certain trials can be justified, even when interim results are inconclusive, to promote the recruitment of participating centers and the practice of a novel way to offer neurovascular care in the presence of uncertainty in the best medical interest of patients., Conclusions: In our opinion, the early publication of inconclusive interim results may increase awareness of the feasibility of surgical care trials., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The Medina embolization device (MED) is a novel, braided self-expanding endovascular device designed to occlude aneurysms by constructing an in situ intrasaccular flow diverter. Although a single device can be positioned at the neck of simple spherical in vitro aneurysms, the best way to occlude more complex in vivo aneurysms (using multiple MEDs or a combination of MEDs and platinum coils) is currently unknown., Methods: Fifty-two aneurysms of 3 different types were created in 31 canines, yielding 48 patent aneurysms. Treatments were randomly allocated by drawing lots: group 1, MEDs alone (n = 16); group 2, MEDs plus standard platinum coils (n = 16); and group 3, control aneurysms treated with coils alone (n = 16). Angiographic results were scored and compared immediately following treatment completion and at 3 months. Specimens were photographed and the extent of neointimal closure of the aneurysmal neck scored, followed by histopathological analyses., Results: Angiographic scores of 0 or 1 (occlusion or near occlusion) were initially obtained in 2 of 16 (12.5%, 95% CI 1.6%-38.3%) group 1 (MEDs alone), 3 of 16 (18.7%, 95% CI 4%-45.6%) group 2 (MEDs plus coils), and 10 of 16 (62.5%, 95% CI 35.4%-84.8%) group 3 (coils alone) aneurysms (p = 0.005). At 3 months, scores of 0 or 1 were found in 11 of 16 (68.7%, 95% CI 41.3%-89.0%) group 1, 9 of 16 (56.2%, 95% CI 29.9%-80.2%) group 2, and 8 of 16 (50%, 95% CI 24.7%-75.3%) group 3 aneurysms (p = 0.82). Neointimal scores were similar for the 3 treated groups (p = 0.66)., Conclusion: Endovascular treatment of experimental aneurysms with MEDs or MEDs and coils showed angiographic occlusion and neointimal scores at 3 months that were similar to those achieved with standard platinum coiling.

Most neurovascular innovations have been introduced by using case series followed by observational studies. A better approach would be a pragmatic randomized trial. Two important aspects of trial design, patient selection and randomized allocation, remain poorly understood. We discuss the role trial methodology can play in the protection of patients being offered innovative treatments., (Published by Elsevier Inc.)

Objective: Ruptured intracranial aneurysms (RIAs) can be managed surgically or endovascularly. In this study, the authors aimed to measure the interobserver agreement in selecting the best management option for various patients with an RIA., Methods: The authors constructed an electronic portfolio of 42 cases of RIA in which an angiographic image along with a brief clinical vignette for each patient were displayed. Undisclosed to the responders was that the RIAs had been categorized as International Subarachnoid Aneurysm Trial (ISAT) (small, anterior-circulation, non-middle cerebral artery location, n = 18) and non-ISAT (n = 22) aneurysms; the non-ISAT group also included 2 basilar apex aneurysms for which a high number of endovascular choices was expected. The portfolio was sent to 132 clinicians who manage patients with RIAs and circulated to members of an American surgical association. Judges were asked to choose between surgical and endovascular management, to indicate their level of confidence in the choice of treatment on a quantitative 0-10 scale, and to determine whether they would include the patient in a randomized trial in which both treatments are compared. Eleven clinicians were asked to respond twice at least 1 month apart. Responses were analyzed using kappa statistics., Results: Eighty-five clinicians (58 cerebrovascular surgeons, 21 interventional neuroradiologists, and 6 interventional neurologists) answered the questionnaire. Overall, endovascular management was chosen more frequently (n = 2136 [59.8%] of 3570 answers). The proportions of decisions to clip were significantly higher for non-ISAT (50.8%) than for ISAT (26.2%) aneurysms (p = 0.0003). Interjudge agreement was only fair (kappa 0.210, 95% CI 0.158-0.276) for all cases and judges, despite high confidence levels (mean score > 8 for all cases). Agreement was no better within subgroups of clinicians with the same specialty, years of experience, or location of practice or across capability groups (ability to clip or coil, or both). When agreement was defined as > 80% of responders choosing the same option, agreement occurred for only 7 of 40 cases, all of which were ISAT aneurysms, for which coiling was preferred., Conclusions: Agreement between clinicians regarding the best management option was infrequent but centered around coiling for some ISAT aneurysms. Surgical clipping was chosen more frequently for non-ISAT aneurysms than for ISAT aneurysms. Patients with such an aneurysm might be candidates for inclusion in randomized trials.

Object: The best management of brain arteriovenous malformation (bAVM) patients remains unknown. Randomized allocation may be more readily accepted when there is uncertainty and disagreement regarding the management of potential participants. In planning for a trial, we aimed to assess variability and agreement among physicians managing bAVM patients., Methods: A portfolio composed of 35 patients was sent to 47 clinicians of various specialties managing bAVM patients. For each patient, physicians were asked their best management decision (surgery/embolization/radiosurgery/conservative), their confidence level, and whether they would include the patient in a randomized trial comparing conservative and curative management. Seven physicians, who had access to all images of each patient, independently responded twice, to assess inter and intra-rater agreement using kappa statistics., Results: The inter-rater agreement (30 raters, including 16 neuroradiologists) for best management decision was only "fair" (κ [95%CI]=0.210[0.157; 0.295]). Agreement remained below 'substantial' (κ<.6) between physicians of the same specialty, and when no distinctions were made between various treatments (when responses were dichotomized as conservative versus curative). With access to all images the inter-rater agreement remained fair. The intra-rater agreement reached "substantial" only for the dichotomized decisions. Responding clinicians were willing to include 54.4% of patients (mainly unruptured bAVMs) in a randomized trial., Conclusion: There is a lack of agreement among clinicians involved in the management of bAVM patients. In this study a substantial proportion of clinicians were willing to offer randomized allocation of management options to a substantial number of patients., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Until recently, the benefits of endovascular treatment in stroke were not proven. Care trials have been designed to simultaneously offer yet-to-be validated interventions and verify treatment outcomes. Our aim was to implement a care trial for patients with acute ischemic stroke., Methods: The study was offered to all patients considered for endovascular management of acute ischemic stroke in one Canadian hospital. Inclusion criteria were broad: onset of symptoms≤5h or at any time in the presence of clinical-imaging mismatch and suspected or demonstrated proximal large vessel occlusion. Exclusion criteria were few: established infarction or hemorrhagic transformation of the target symptomatic territory and poor 3-month prognosis. The primary outcome was mRS≤2 at 3 months. Patients were randomly allocated to standard care or standard care plus endovascular treatment. ClinicalTrials.gov: Identifier NCT02157532., Results: Seventy-seven patients were recruited in 19 months (March 2013-October 2014) at a single center. Randomized allocation was interrupted when other trials showed the benefits of endovascular therapy. At 3 months, 20 of 40 patients (50.0%; 95% CI: 35%-65%) in the intervention group had reached the primary outcome, compared to 14 of 37 patients (37.8%; 95% CI: 24%-54%) in the control group (P=0.36). Eleven patients in the intervention group died within 3 months compared to 9 patients in the standard care group., Conclusion: A care trial was implemented to offer verifiable care to acute stroke patients. This approach offers a promising means to manage clinical dilemmas and guide uncertain practices., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: Randomized allocation of treatment options is not well accepted within the clinical community. Some methods of implementation may be received more favorably than others. Prerandomization may be an acceptable means to facilitate recruitment in some clinical trials., Methods: We first compare randomization and prerandomization using illustrative neurovascular trials. We review some problems with conventional trials, Zelen's prerandomization as an alternative method, and the ethical issues that have surrounded prerandomization since its inception in a historic trial. Conventional and Zelen's randomization are then compared with other means to provide and verify care in the context of clinical uncertainty., Results: The major problem with conventional randomization is that consent is requested for 2 management options, one of which the patient will not receive. The problem with prerandomization is that treatment is allocated before the patient has consented to trial participation. Prerandomization may trade recruitment difficulties for excessive crossovers. However, other ways to practice under uncertainty and verify patient outcomes, such as case series and registries, are more ethically and scientifically problematic., Conclusions: Until the ethical functions of randomized allocation of selected treatment options in the care of patients are recognized by the neurovascular community, Zelen's prerandomization may help recruitment into difficult trials and contribute a means to provide best possible care in the presence of uncertainty., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Although the common carotid artery is the second most common site for extracranial carotid artery stenosis, complete symptomatic occlusion in the absence of devastating stroke is rare. We present a case of complete common carotid artery occlusion failing medical management and requiring endovascular intervention. The clinical presentation, diagnostic investigations, and management of complete carotid artery occlusions are discussed.

Objective: Flow diverters (FDs) are increasingly used to treat difficult intracranial aneurysms. The objective of this study was to test whether treatment challenges posed by giant curved sidewall (cSW) and endwall bifurcation (EwB) aneurysms can be overcome with the use of very-low-porosity devices., Methods: Large and giant EwB (n = 12) and cSW aneurysms (n = 5) were constructed in 17 dogs. EwB aneurysms were treated with 48 (n = 4), 64 (n = 4), or two overlapping 64-wire low-porosity devices (n = 4), whereas all cSW aneurysms were treated with single 64-wire devices. Angiographic results were recorded immediately and at 12 weeks before euthanasia. Pathologic specimens were photographed and neointimal coverage of devices measured and scored., Results: By 12 weeks, 1 of 12 EwB and 1 of 5 cSW aneurysms were occluded. All other aneurysms were patent. Device-related arterial stenoses occurred in 13 of 17 animals, hemodynamically significant in two. All branches jailed by the FDs remained patent. There was a significant correlation between angiographic scores and the degree of neointima formation on the device (Rho = 0.527; P = 0.04). Failures of aneurysm occlusion could be explained by holes, sometimes barely visible, in the neointima that formed over FDs., Conclusion: Low-porosity FDs fail to reliably occlude experimental giant EwB and cSW aneurysms., (Copyright © 2014 Elsevier Inc. All rights reserved.)