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Background and purposeIntracarotid arterial infusion of nonionic, low-osmolal iohexol contrast medium has been associated with increased intracranial hemorrhage in a rat middle cerebral artery occlusion model compared with saline infusion. Iso-osmolal iodixanol (290 mOsm/kg H2O) infusion demonstrated smaller infarcts and less intracranial hemorrhage compared with low-osmolal iopamidol and saline. No studies comparing iodinated radiographic contrast media in human stroke have been performed, to our knowledge. We hypothesized that low-osmolal contrast media may be associated with worse outcomes compared with iodixanol in the Interventional Management of Stroke III Trial (IMS III).Materials and methodsWe reviewed prospective iodinated radiographic contrast media data for 133 M1 occlusions treated with endovascular therapy. We compared 5 prespecified efficacy and safety end points (mRS 0-2 outcome, modified TICI 2b-3 reperfusion, asymptomatic and symptomatic intracranial hemorrhage, and mortality) between those receiving iodixanol (n = 31) or low-osmolal contrast media (n = 102). Variables imbalanced between iodinated radiographic contrast media types or associated with outcome were considered potential covariates for the adjusted models. In addition to the iodinated radiographic contrast media type, final covariates were those selected by using the stepwise method in a logistic regression model. Adjusted relative risks were then estimated by using a log-link regression model.ResultsOf baseline or endovascular therapy variables potentially linked to outcome, prior antiplatelet agent use was more common and microcatheter iodinated radiographic contrast media injections were fewer with iodixanol. Relative risk point estimates are in favor of iodixanol for the 5 prespecified end points with M1 occlusion. The percentage of risk differences are numerically greater for microcatheter injections with iodixanol.ConclusionsWhile data favoring the use of iso-osmolal iodixanol for reperfusion of M1 occlusion following IV rtPA are inconclusive, potential pathophysiologic mechanisms suggesting clinical benefit warrant further investigation.

The surgical management of carotid paragangliomas can be problematic. A multidisciplinary approach was used to include vascular surgery, otolaryngology, and neuroradiology to treat these patients over 9 years. From January 1992 to July 2001, a multidisciplinary team evaluated patients with carotid paragangliomas. Analyzed patient data included age, gender, diagnostic evaluation, tumor size, preoperative tumor embolization, operative exposure, need for extracranial arterial sacrifice/reconstruction, postoperative morbidity including cranial nerve dysfunction, and long-term follow-up. Twenty-five carotid paragangliomas in 20 patients underwent multidisciplinary evaluation and management. Average age was 51 years (range, 28-83 years), and 52% were male. Diagnostic evaluation included computed tomography in 76%, magnetic resonance imaging/magnetic resonance angiography in 52%, catheter angiography in 60%, and duplex ultrasonography in 16%. An extended neck exposure was required in 11 cases (44%), mandibulotomy was used once (4%), and mandibular subluxation was never required. The external carotid artery (ECA) was sacrificed in 8 cases (32%). The carotid bifurcation was resected in 1 patient (4%) requiring interposition reconstruction of the internal carotid artery. Preoperative tumor embolization was performed for 13 tumors (52%). Operative blood loss for patients undergoing preoperative embolization (Group I) was comparable to the nonembolized group (group II): group I lost 365 +/-180 mL versus 360 +/- 101 mL for group II (P = .48). This occurred despite larger tumors (group I - 4.2 cm versus group II - 2.1 cm, P = .03) and a higher mean Shamblin class (group I - 2.5 versus group II - 1.45, P = .001) for group I. There were no perioperative mortalities. Transient cranial nerve dysfunction occurred in 13 CBTs (52%), 2 (8%) of which remained present after 4 months. Patients with carotid paragangliomas benefit from a multidisciplinary team approach. Neuroradiology has been used for selective preoperative embolization, which has decreased estimated blood loss during excision of larger complex tumors. A combined surgical team of otolaryngology and vascular surgery provides for exposure of the distal internal carotid artery as high as the skull base, limited permanent cranial nerve dysfunction, and selective early division and excision of the external carotid artery for complete tumor resection. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cervical spine axial MRI T2-hyperintense fluid signal of the anterior median fissure and round hyperintense foci resembling either the central canal or base of the anterior median fissure are associated with a craniocaudad sagittal line, also simulating the central canal. On the basis of empiric observation, we hypothesized that hyperintense foci, the anterior median fissure, and the sagittal line are seen more frequently in patients with Chiari malformation type I, and the sagittal line may be the base of the anterior median fissure in some patients., Materials and Methods: Saggital line incidence and the incidence/frequency of hyperintense foci and anterior median fissure in 25 patients with Chiari I malformation and 25 contemporaneous age-matched controls were recorded in this prospective exploratory study as either combined (hyperintense foci+anterior median fissure in the same patient), connected (anterior median fissure extending to and appearing to be connected with hyperintense foci), or alone as hyperintense foci or an anterior median fissure. Hyperintense foci and anterior median fissure/patient, hyperintense foci/anterior median fissure ratios, and anterior median fissure extending to and appearing to be connected with hyperintense foci were compared in all, in hyperintense foci+anterior median fissure in the same patient, and in anterior median fissure extending to and appearing to be connected with hyperintense foci in patients with Chiari I malformation and controls., Results: Increased sagittal line incidence (56%), hyperintense foci (8.5/patient), and anterior median fissure (4.0/patient) frequency were identified in patients with Chiari I malformation versus controls (28%, 3.9/patient, and 2.7/patient, respectively). Increased anterior median fissure/patient, decreasing hyperintense foci/anterior median fissure ratio, and increasing anterior median fissure extending to and appearing to be connected with hyperintense foci/patient were identified in Chiari subgroups. A 21%-58% increase in observed anterior median fissure extending to and appearing connected to hyperintense foci in the entire cohort and multiple sagittal line subgroups compared with predicted occurred., Conclusions: In addition to the anticipated increased incidence/frequency of sagittal line and hyperintense foci in patients with Chiari I malformation, an increased incidence and frequency of anterior median fissure and anterior median fissure extending to and appearing to be connected with hyperintense foci/patient were identified. We believe an anterior median fissure may contribute to a saggital line appearance in some patients with Chiari I malformation. While thin saggital line channels are usually ascribed to the central canal, we believe some may be due to the base of the anterior median fissure, created by pulsatile CSF hydrodynamics., (© 2021 by American Journal of Neuroradiology.)

OBJECTIVE The impact of extracranial carotid stenosis on interventional revascularization of acute anterior circulation stroke is unknown. The authors examined the effects of high-grade carotid stenosis on the results of endovascular treatment of patients in the Interventional Management of Stroke (IMS)-III trial. METHODS The 278 patients in the endovascular arm of the IMS-III trial were categorized according to the degree of carotid stenosis as determined by angiography. In comparing patients with severe stenosis or occlusion (≥ 70%) to those without severe stenosis (< 70%), the authors evaluated the time to endovascular reperfusion, modified Thrombolysis in Cerebrovascular Infarction (mTICI) scores, 24-hour mean infarct volumes, symptomatic intracerebral hemorrhage rates, and modified Rankin Scale (mRS) scores at 90 days. RESULTS Compared with the 249 patients with less than 70% stenosis, patients with severe stenosis (n = 29) were found to have a significantly longer mean time to reperfusion (105.7 vs 77.7 minutes, p = 0.004); differences in mTICI scores, infarct volumes, hemorrhage rates, and mRS scores at 90 days did not reach statistical significance. Multiple regression analysis revealed that severe carotid stenosis (p < 0.0001) and higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (p = 0.004) were associated with an increase in time to reperfusion. Older age (p < 0.0001), higher NIHSS score (p < 0.0001), and the absence of reperfusion (p = 0.001) were associated with worse clinical outcomes. CONCLUSIONS Severe ipsilateral ICA stenosis was associated with a significantly longer time to reperfusion in the IMS-III trial. Although these findings may not translate directly to modern devices, this 28-minute delay in reperfusion has significant implications, raising concern over the treatment of tandem ICA stenosis and downstream large-vessel occlusion.

Background: Examination of linked data on patient outcomes and cost of care may help identify areas where stroke care can be improved. We report on the association between variations in stroke severity, patient outcomes, cost, and treatment patterns observed over the acute hospital stay and through the 12-month follow-up for subjects receiving endovascular therapy compared to intravenous tissue plasminogen activator alone in the IMS (Interventional Management of Stroke) III Trial., Methods and Results: Prospective data collected for a prespecified economic analysis of the trial were used. Data included hospital billing records for the initial stroke admission and subsequent detailed resource use after the acute hospitalization collected at 3, 6, 9, and 12 months. Cost of follow-up care varied 6-fold for patients in the lowest (0-1) and highest (20+) National Institutes of Health Stroke Scale category at 5 days, and by modified Rankin Scale at 3 months. The kind of resources used postdischarge also varied between treatment groups. Incremental short-term cost-effectiveness ratios varied greatly when treatments were compared for patient subgroups. Patient subgroups predefined by stroke severity had incremental cost-effectiveness ratios of $97 303/quality-adjusted life year (severe stroke) and $3 187 805/quality-adjusted life year (moderately severe stroke)., Conclusions: Detailed economic and resource utilization data from IMS III provide powerful evidence for the large effect that patient outcome has on the economic value of medical and endovascular reperfusion therapies. These data can be used to inform process improvements for stroke care and to estimate the cost-effectiveness of endovascular therapy in the US health system for stroke intervention trials., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Registration number: NCT00359424., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background and Purpose: Hyperintense fluid-signal anterior median fissure and hyperintense foci resembling the central canal are seen on cervical spine axial T2 MR imaging. They may also be associated with a channel-like T2-hyperintense craniocaudad line on sagittal images. We hypothesized that the hyperintense foci and the sagittal line may represent the base of the anterior median fissure., Materials and Methods: In this exploratory study, 358 cervical MR images were analyzed for recording and comparing the incidence/numbers of hyperintense foci, anterior median fissure, and sagittal line as hyperintense foci, anterior median fissure, and sagittal line per patient when present alone or together, both with and without the sagittal line., Results: Hyperintense foci were identified on 238/358 (66.5%) studies; an anterior median fissure, on 218/358 (60.9%). The hyperintense foci/anterior median fissure ratio was 3.7/2.3 ( P = .00001). Anterior median fissures were seen alone less commonly than hyperintense foci were seen alone ( P = .045). We identified increased anterior median fissure/patient in a hyperintense foci +anterior median fissure group compared with an anterior median fissure-only group (4.0 versus 3.2, P = .05), with similar hyperintense foci/patient in the hyperintense foci+anterior median fissure and hyperintense foci-only groups (5.5 versus 5.8, P = .35), and proportional distribution of both across the hyperintense foci+anterior median fissure subgroups (hyperintense foci/anterior median fissure ratio, 1.3). The sagittal line in 89 (24.9%) patients was associated with increased hyperintense foci and anterior median fissure/patient. Greater correlation of anterior median fissure/patient to sagittal line presence was seen in sagittal line subgroup analysis., Conclusions: This exploratory analysis found an increased anterior median fissure per patient in conjunction with hyperintense foci presence, a proportional increase of both across the hyperintense foci+anterior median fissure group, and greater correlation of anterior median fissure per patient with the sagittal line. These findings suggest that anterior median fissure and hyperintense foci are structurally related, that hyperintense foci may commonly be the base of the anterior median fissure, and that the sagittal line is a manifestation primarily of an anterior median fissure, occasionally appearing as channels that may simulate the central canal., (© 2017 by American Journal of Neuroradiology.)

Background and Purpose: Uncertainty persists regarding the safety and efficacy of endovascular therapy of M2 occlusions following IV tPA. We reviewed the impact of revascularization on clinical outcomes in 83 patients with M2 occlusions in the Interventional Management of Stroke III trial according to specific M1-M2 segment anatomic features., Materials and Methods: Perfusion of any M2 branch distinguished M2-versus-M1 occlusion. Prespecified modified TICI and arterial occlusive lesion revascularization and clinical mRS 0-2 end points at 90 days for endovascular therapy-treated M2 occlusions were analyzed. Post hoc analyses of the relationship of outcomes to multiple baseline angiographic M2 and M1 subgroup characteristics were performed., Results: Of 83 participants with M2 occlusion who underwent endovascular therapy, 41.0% achieved mRS 0-2 at 90 days, including 46.6% with modified TICI 2-3 reperfusion compared with 26.1% with modified TICI 0-1 reperfusion (risk difference, 20.6%; 95% CI, -1.4%-42.5%). mRS 0-2 outcome was associated with reperfusion for M2 trunk (n = 9) or M2 division (n = 42) occlusions, but not for M2 branch occlusions (n = 28). Of participants with trunk and division occlusions, 63.2% with modified TICI 2a and 42.9% with modified TICI 2b reperfusion achieved mRS 0-2 outcomes; mRS 0-2 outcomes for M2 trunk occlusions (33%) did not differ from distal (38.2%) and proximal (26.9%) M1 occlusions., Conclusions: mRS 0-2 at 90 days was dependent on reperfusion for M2 trunk but not for M2 branch occlusions. For M2 division occlusions, good outcome with modified TICI 2b reperfusion did not differ from that in modified TICI 2a. M2 segment definition and occlusion location may contribute to differences in revascularization and good outcome between Interventional Management of Stroke III and other endovascular therapy studies., (© 2017 by American Journal of Neuroradiology.)

Background: Prompt revascularization is the main goal of acute ischemic stroke treatment. We examined which revascularization scale - reperfusion (modified Treatment in Cerebral Infarctions, mTICI) or recanalization (Arterial Occlusive Lesion, AOL) - better predicted the clinical outcome in ischemic stroke participants treated with endovascular therapy (EVT). Additionally, we determined the optimal thresholds for the predictive accuracy of each scale., Methods: We included participants from the Interventional Management of Stroke (IMS) III trial with complete occlusion in the internal carotid artery terminus or proximal middle cerebral artery (M1 or M2) who completed EVT within 7 h of symptom onset. The abilities of the AOL and mTICI scales to predict a favorable outcome (defined as a modified Rankin Scale score of 0-2 at 3 months) were compared by receiver operating characteristic analyses. The maximal sensitivity and specificity for each revascularization scale were established., Results: Among 240 participants who met the study inclusion criteria, 79 (33%) achieved a favorable outcome. Higher scores of mTICI and AOL increased the likelihood of a favorable outcome (2.7% with mTICI 0 vs. 83.3% with mTICI 3, and 3.0% with AOL 0 vs. 43% with AOL 3). The accuracy of mTICI reperfusion and AOL recanalization for a favorable outcome prediction was similar, with optimal thresholds of mTICI 2b/3 and AOL 3, respectively., Conclusion: Reperfusion (mTICI) and recanalization (AOL) predicted a favorable clinical outcome with comparable accuracy in ischemic stroke participants treated with EVT. Optimal revascularization goals to maximize clinical outcome (modified Rankin Scale score of 0-2) consisted of complete recanalization (AOL 3) and reperfusion of at least 50% of the arterial tree of the symptomatic artery (mTICI 2b/3) in the IMS III trial setting.

Background and Purpose: The importance of time in acute stroke is well-established. Using the Interventional Management of Stroke III trial data, we explored the effect of multimodal imaging (CT perfusion and/or CT angiography) versus noncontrast CT alone on time to treatment and outcomes., Materials and Methods: We examined 3 groups: 1) subjects with baseline CTP and CTA (CTP+CTA), 2) subjects with baseline CTA without CTP (CTA), and 3) subjects with noncontrast head CT alone. The demographics, treatment time intervals, and clinical outcomes in these groups were studied., Results: Of 656 subjects enrolled in the Interventional Management of Stroke III trial, 90 (13.7%) received CTP and CTA, 216 (32.9%) received CTA (without CTP), and 342 (52.1%) received NCCT alone. Median times for the CTP+CTA, CTA, and NCCT groups were as follows: stroke onset to IV tPA (120.5 versus 117.5 versus 120 minutes; P = .5762), IV tPA to groin puncture (77.5 versus 81 versus 91 minutes; P = .0043), groin puncture to endovascular therapy start (30 versus 38 versus 44 minutes; P = .0001), and endovascular therapy start to end (63 versus 46 versus 74 minutes; P < .0001). Compared with NCCT, the CTA group had better outcomes in the endovascular arm (OR, 2.12; 95% CI, 1.36-3.31; adjusted for age, NIHSS score, and time from onset to IV tPA). The CTP+CTA group did not have better outcomes compared with the NCCT group., Conclusions: Use of CTA with or without CTP did not delay IV tPA or endovascular therapy compared with NCCT in the Interventional Management of Stroke III trial., (© 2016 by American Journal of Neuroradiology.)

Objective: To assess whether the association between reperfusion and improved clinical outcomes after stroke differs depending on the site of the arterial occlusive lesion (AOL)., Methods: We pooled data from Solitaire With the Intention for Thrombectomy (SWIFT), Solitaire FR Thrombectomy for Acute Revascularisation (STAR), Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), and Interventional Management of Stroke Trial (IMS III) to compare the strength of the associations between reperfusion and clinical outcomes in patients with internal carotid artery (ICA), proximal middle cerebral artery (MCA) (M1), and distal MCA (M2/3/4) occlusions., Results: Among 710 included patients, the site of the AOL was the ICA in 161, the proximal MCA in 389, and the distal MCA in 160 patients (M2 = 131, M3 = 23, and M4 = 6). Reperfusion was associated with an increase in the rate of good functional outcome (modified Rankin Scale [mRS] score 0-2) in patients with ICA (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.7-7.2) and proximal MCA occlusions (OR 6.2, 95% CI 3.8-10.2), but not in patients with distal MCA occlusions (OR 1.4, 95% CI 0.8-2.6). Among patients with M2 occlusions, a subset of the distal MCA cohort, reperfusion was associated with excellent functional outcome (mRS 0-1; OR 2.2, 95% CI 1.0-4.7)., Conclusions: The association between endovascular reperfusion and better clinical outcomes is more profound in patients with ICA and proximal MCA occlusions compared to patients with distal MCA occlusions. Because there are limited data from randomized controlled trials on the effect of endovascular therapy in patients with distal MCA occlusions, these results underscore the need for inclusion of this subgroup in future endovascular therapy trials., (© 2016 American Academy of Neurology.)

Background and Purpose: We assessed the effect of endovascular treatment in acute ischemic stroke patients with severe neurological deficit (National Institutes of Health Stroke Scale score, ≥20) after a prespecified analysis plan., Methods: The pooled analysis of the Interventional Management of Stroke III (IMS III) and Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands (MR CLEAN) trials included participants with an National Institutes of Health Stroke Scale score of ≥20 before intravenous tissue-type plasminogen activator (tPA) treatment (IMS III) or randomization (MR CLEAN) who were treated with intravenous tPA ≤3 hours of stroke onset. Our hypothesis was that participants with severe stroke randomized to endovascular therapy after intravenous tPA would have improved 90-day outcome (distribution of modified Rankin Scale scores), when compared with those who received intravenous tPA alone., Results: Among 342 participants in the pooled analysis (194 from IMS III and 148 from MR CLEAN), an ordinal logistic regression model showed that the endovascular group had superior 90-day outcome compared with the intravenous tPA group (adjusted odds ratio, 1.78; 95% confidence interval, 1.20-2.66). In the logistic regression model of the dichotomous outcome (modified Rankin Scale score, 0-2, or functional independence), the endovascular group had superior outcomes (adjusted odds ratio, 1.97; 95% confidence interval, 1.09-3.56). Functional independence (modified Rankin Scale score, ≤2) at 90 days was 25% in the endovascular group when compared with 14% in the intravenous tPA group., Conclusions: Endovascular therapy after intravenous tPA within 3 hours of symptom onset improves functional outcome at 90 days after severe ischemic stroke., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424 (IMS III) and ISRCTN10888758 (MR CLEAN)., (© 2015 American Heart Association, Inc.)

Background: Interventional Management of Stroke III did not show that combining IV recombinant tissue plasminogen activator (rt-PA) with endovascular therapies (EVTs) is better than IV rt-PA alone., Objective: To report efficacy and safety results for EVT of intracranial internal carotid artery (ICA) and middle cerebral artery trunk (M1) occlusion., Methods: Five revascularization methods for persistent occlusions after IV rt-PA treatment were evaluated for prespecified primary and secondary endpoints, after accounting for differences in key baselines variables using propensity scores. Revascularization was scored using the arterial occlusive lesion (AOL) and the modified Thrombolysis in Cerebral Ischemia (mTICI) scores., Results: EVT of 200 subjects with intracranial ICA or M1 occlusion resulted in 81.5% AOL 2-3 recanalization, in addition to 76% mTICI 2-3 and 42.5% mTICI 2b-3 reperfusion. Adverse events included symptomatic intracranial hemorrhage (SICH) (8.0%), vessel perforations (1.5%), and new emboli (14.9%). EVT techniques used were standard microcatheter n=51; EKOS n=14; Merci n=77; Penumbra n=39; Solitaire n=4; multiple n=15. Good clinical outcome was associated with both TICI 2-3 and TICI 2b-3 reperfusion. Neither modified Rankin scale (mRS) 0-2 (28.5%), nor 90-day mortality (28.5%), nor asymptomatic ICH (36.0%) differed among revascularization methods after propensity score adjustment for subjects with intracranial ICA or M1 occlusion., Conclusions: Good clinical outcome was associated with good reperfusion for ICA and M1 occlusion. No significant differences in efficacy or safety among revascularization methods were demonstrated after adjustment. Lack of high-quality reperfusion, adverse events, and prolonged time to treatment contributed to lower-than-expected mRS 0-2 outcomes and study futility compared with IV rt-PA., Trial Registration Number: NCT00359424., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background and Purpose: Intracarotid arterial infusion of nonionic, low-osmolal iohexol contrast medium has been associated with increased intracranial hemorrhage in a rat middle cerebral artery occlusion model compared with saline infusion. Iso-osmolal iodixanol (290 mOsm/kg H2O) infusion demonstrated smaller infarcts and less intracranial hemorrhage compared with low-osmolal iopamidol and saline. No studies comparing iodinated radiographic contrast media in human stroke have been performed, to our knowledge. We hypothesized that low-osmolal contrast media may be associated with worse outcomes compared with iodixanol in the Interventional Management of Stroke III Trial (IMS III)., Materials and Methods: We reviewed prospective iodinated radiographic contrast media data for 133 M1 occlusions treated with endovascular therapy. We compared 5 prespecified efficacy and safety end points (mRS 0-2 outcome, modified TICI 2b-3 reperfusion, asymptomatic and symptomatic intracranial hemorrhage, and mortality) between those receiving iodixanol (n = 31) or low-osmolal contrast media (n = 102). Variables imbalanced between iodinated radiographic contrast media types or associated with outcome were considered potential covariates for the adjusted models. In addition to the iodinated radiographic contrast media type, final covariates were those selected by using the stepwise method in a logistic regression model. Adjusted relative risks were then estimated by using a log-link regression model., Results: Of baseline or endovascular therapy variables potentially linked to outcome, prior antiplatelet agent use was more common and microcatheter iodinated radiographic contrast media injections were fewer with iodixanol. Relative risk point estimates are in favor of iodixanol for the 5 prespecified end points with M1 occlusion. The percentage of risk differences are numerically greater for microcatheter injections with iodixanol., Conclusions: While data favoring the use of iso-osmolal iodixanol for reperfusion of M1 occlusion following IV rtPA are inconclusive, potential pathophysiologic mechanisms suggesting clinical benefit warrant further investigation., (© 2015 by American Journal of Neuroradiology.)

Rationale: Endovascular treatment has been shown to restore blood flow effectively. Second-generation medical devices such as stent retrievers are now showing overwhelming efficacy in clinical trials, particularly in conjunction with intravenous recombinant tissue plasminogen activator., Aims and Design: This statistical analysis plan utilizing a novel, sequential approach describes a prospective, individual patient data analysis of endovascular therapy in conjunction with intravenous recombinant tissue plasminogen activator agreed upon by the Thrombectomy and Tissue Plasminogen Activator Collaborative Group., Study Outcomes: This protocol will specify the primary outcome for efficacy, as 'favorable' outcome defined by the ordinal distribution of the modified Rankin Scale measured at three-months poststroke, but with modified Rankin Scales 5 and 6 collapsed into a single category. The primary analysis will aim to answer the questions: 'what is the treatment effect of endovascular therapy with intravenous recombinant tissue plasminogen activator compared to intravenous tissue plasminogen activator alone on full scale modified Rankin Scale at 3 months?' and 'to what extent do key patient characteristics influence the treatment effect of endovascular therapy?'. Key secondary outcomes include effect of endovascular therapy on death within 90 days; analyses of modified Rankin Scale using dichotomized methods; and effects of endovascular therapy on symptomatic intracranial hemorrhage. Several secondary analyses will be considered as well as expanding patient cohorts to intravenous recombinant tissue plasminogen activator-ineligible patients, should data allow., Discussion: This collaborative meta-analysis of individual participant data from randomized trials of endovascular therapy vs. control in conjunction with intravenous thrombolysis will demonstrate the efficacy and generalizability of endovascular therapy with intravenous thrombolysis as a concomitant medication., (© 2015 World Stroke Organization.)

Background and Purpose: Until recently, acute ischemic stroke (AIS) trials have failed to show a benefit of endovascular therapy compared with standard therapy, leading some authors to recommend decreasing the time from ictus to revascularization to improve outcomes. We hypothesize that improving patient selection using the capillary index score (CIS) may also be a useful strategy., Methods: CIS was calculated, blinded to outcome, from pretreatment diagnostic cerebral angiograms for 78 subjects in the Interventional Management of Stroke III database with internal carotid artery and middle cerebral artery trunk occlusion. The CIS was dichotomized into favorable (fCIS=2 or 3) and poor (pCIS=0 or 1). Outcomes were categorized based on the modified Rankin Scale score at 90 days (0-2 considered a good outcome). Modified thrombolysis in cerebral infarction score 2b or 3 was considered good revascularization. Multivariable logistic regression was performed to relate CIS, time from ictus to revascularization, modified thrombolysis in cerebral infarction score, and National Institue of Health Stroke Scale score to good outcomes., Results: Only CIS and modified thrombolysis in cerebral infarction scores were correlated with good outcomes (P<0.01). Patients with fCIS and good revascularization achieved 71% modified Rankin Scale≤2, compared with 13% for patients with pCIS and good revascularization., Conclusions: In this subset of patients from the Interventional Management of Stroke III Trial, CIS and modified thrombolysis in cerebral infarction were strong predictors of outcome after endovascular reperfusion. Using the CIS to improve patient selection could be a powerful strategy to improve rate of good outcomes in endovascular therapy. A randomized trial is needed., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424., (© 2015 American Heart Association, Inc.)

Background and Purpose: Randomized trials have indicated a benefit for endovascular therapy in appropriately selected stroke patients at 3 months, but data regarding outcomes at 12 months are currently lacking., Methods: We compared functional and quality-of-life outcomes at 12 months overall and by stroke severity in stroke patients treated with intravenous tissue-type plasminogen activator followed by endovascular treatment as compared with intravenous tissue-type plasminogen activator alone in the Interventional Management of Stroke III Trial. The key outcome measures were a modified Rankin Scale score ≤2 (functional independence) and the Euro-QoL EQ-5D, a health-related quality-of-life measure., Results: 656 subjects with moderate-to-severe stroke (National Institutes of Health Stroke Scale ≥8) were enrolled at 58 centers in the United States (41 sites), Canada (7), Australia (4), and Europe (6). There was an interaction between treatment group and stroke severity in the repeated measures analysis of modified Rankin Scale ≤2 outcome (P=0.039). In the 204 participants with severe stroke (National Institutes of Health Stroke Scale ≥20), a greater proportion of the endovascular group had a modified Rankin Scale ≤2 (32.5%) at 12 months as compared with the intravenous tissue-type plasminogen activator group (18.6%, P=0.037); no difference was seen for the 452 participants with moderately severe strokes (55.6% versus 57.7%). In participants with severe stroke, the endovascular group had 35.2 (95% confidence interval: 2.1, 73.3) more quality-adjusted-days over 12 months as compared with intravenous tissue-type plasminogen activator alone., Conclusions: Endovascular therapy improves functional outcome and health-related quality-of-life at 12 months after severe ischemic stroke., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424., (© 2015 American Heart Association, Inc.)

Background and Purpose: In the Interventional Management of Stroke (IMS) III trial, we sought to demonstrate evidence of a differential treatment effect of endovascular treatment of acute ischemic stroke compared with intravenous tissue-type plasminogen activator, according to baseline collateral status measured using computed tomographic angiography., Methods: Of 656 patients enrolled in Interventional Management of Stroke III trial, 306 had baseline computed tomographic angiography. Of these, 185 patients had M1 middle cerebral artery ± intracranial internal carotid artery occlusion, where baseline collateral status could be measured. Collateral status was assessed by consensus using 3 different ordinal scales and categorized as good, intermediate, and poor. Multivariable modeling was used to assess the effect of collateral status and treatment type on clinical outcome by modified Rankin Scale (mRS 0-2, mRS 0-1, and the ordinal mRS)., Results: Of 185 patients, 126 randomized to endovascular therapy (87.6% recanalized, 41.3% 90-day mRS 0-2) and 59 to intravenous tissue-type plasminogen activator only (60.5% recanalized, 30.5% 90-day mRS 0-2). In multivariable modeling, collateral status was a significant predictor of all clinical outcomes (P<0.05). Maximal benefit with endovascular treatment across all clinical outcomes was seen in patients with intermediate collaterals, some benefit in patients with good collaterals, and none in patients with poor collaterals, although small sample size limited the power of the analysis to show a statistically significant interaction between collateral status and treatment type (P>0.05)., Conclusion: Using data from a large randomized controlled trial (IMS III), we show that baseline computed tomographic angiography collaterals are a robust determinant of final clinical outcome and could be used to select patients for endovascular therapy., Clinical Trial Registration: URL: http://www.clinicaltrials.gov/ct2/show/. Unique identifier: 0020NCT00359424., (© 2015 American Heart Association, Inc.)

Object: The role of endovascular therapy in patients with acute ischemic stroke and a solitary M2 occlusion remains unclear. Through a pooled analysis of 3 interventional stroke trials, the authors sought to analyze the impact of successful early reperfusion of M2 occlusions on patient outcome., Methods: Patients with a solitary M2 occlusion were identified from the Prolyse in Acute Cerebral Thromboembolism (PROACT) II, Interventional Management of Stroke (IMS), and IMS II trial databases and were divided into 2 groups: successful reperfusion (thrombolysis in cerebral infarction [TICI] 2-3) at 2 hours and failed reperfusion (TICI 0-1) at 2 hours. Baseline characteristics and clinical outcomes were compared., Results: Sixty-three patients, 40 from PROACT II and 23 from IMS and IMS II, were identified. Successful early angiographic reperfusion (TICI 2-3) was observed in 31 patients (49.2%). No statistically significant difference in the rates of intracerebral hemorrhage (60.9% vs 47.6%, p = 0.55) or mortality (19.4% vs 15.6%, p = 0.75) was observed. However, there was a trend toward higher incidence of symptomatic hemorrhage in the TICI 2-3 group (17.4% vs 0%, p = 0.11). There was also a trend toward higher baseline glucose levels in this group (151.5 mg/dl vs 129.6 mg/ dl, p = 0.09). Despite these differences, the rate of functional independence (modified Rankin Scale Score 0-2) at 3 months was similar (TICI 2-3, 58.1% vs TICI 0-1, 53.1%; p = 0.80)., Conclusions: A positive correlation between successful early reperfusion and clinical outcome could not be demonstrated for patients with M2 occlusion. Irrespective of reperfusion status, such patients have better outcomes than those with more proximal occlusions, with more than 50% achieving functional independence at 3 months.

Background and Purpose: We explored changes in the patient population and practice of endovascular therapy during the course of the Interventional Management of Stroke (IMS) III Trial., Methods: Changes in baseline characteristics, use of baseline CT angiography, treatment times and specifics, and outcomes were compared between the first 4 protocols and the fifth and final protocol., Results: Compared with subjects treated in the first 4 protocol versions (n=610), subjects treated in fifth and final protocol (n=46) were older (75 versus 68 years, P<0.0002) and less likely to have a pretreatment Rankin of 0 (76% versus 89%, P=0.01), were more likely to have a pretreatment CT angiography (65% versus 45%, P=0.009), had quicker median times in the endovascular arm from onset to start of intra-arterial therapy (209 versus 250 minutes, P=0.002) and to reperfusion (269 versus 344 minutes, P<0.0001), had a higher mean dose of total tissue-type plasminogen activator in the endovascular arm (74.0 versus 63.7 mg, P<0.0001), and were less likely to receive intra-arterial tissue-type plasminogen activator as part of the endovascular procedure (16% versus 44%, P=0.015). There were no significant differences in functional and safety outcomes between subjects treated in the 2 treatments arms in either the first 4 protocols or fifth protocol although the small sample size in the fifth protocol provided limited power., Conclusions: Endovascular technology and diagnostic approaches to acute stroke patients changed substantially during the IMS III Trial. Efforts to decrease the time to delivery of endovascular therapy were successful., (© 2014 American Heart Association, Inc.)

Background and Purpose: Our objective was to use decision analytic modeling to compare 2 treatment strategies of intravenous recombinant tissue-type plasminogen activator (r-tPA) alone versus combined intravenous r-tPA/endovascular therapy in a subgroup of patients with large vessel (internal carotid artery terminus, M1, and M2) occlusion based on varying times to angiographic reperfusion and varying rates of reperfusion., Methods: We developed a decision model using Interventional Management of Stroke (IMS) III trial data and comprehensive literature review. We performed 1-way sensitivity analyses for time to reperfusion and 2-way sensitivity for time to reperfusion and rate of reperfusion success. We also performed probabilistic sensitivity analyses to address uncertainty in total time to reperfusion for the endovascular approach., Results: In the base case, endovascular approach yielded a higher expected utility (6.38 quality-adjusted life years) than the intravenous-only arm (5.42 quality-adjusted life years). One-way sensitivity analyses demonstrated superiority of endovascular treatment to intravenous-only arm unless time to reperfusion exceeded 347 minutes. Two-way sensitivity analysis demonstrated that endovascular treatment was preferred when probability of reperfusion is high and time to reperfusion is small. Probabilistic sensitivity results demonstrated an average gain for endovascular therapy of 0.76 quality-adjusted life years (SD 0.82) compared with the intravenous-only approach., Conclusions: In our post hoc model with its underlying limitations, endovascular therapy after intravenous r-tPA is the preferred treatment as compared with intravenous r-tPA alone. However, if time to reperfusion exceeds 347 minutes, intravenous r-tPA alone is the recommended strategy. This warrants validation in a randomized, prospective trial among patients with large vessel occlusions., (© 2014 American Heart Association, Inc.)

Purpose: To use baseline computed tomographic (CT) angiography to analyze imaging and clinical end points in an Interventional Management of Stroke III cohort to identify patients who would benefit from endovascular stroke therapy., Materials and Methods: The primary clinical end point was 90-day dichotomized modified Rankin Scale (mRS) score. Secondary end points were 90-day mRS score distribution and 24-hour recanalization. Prespecified subgroup was baseline proximal occlusions (internal carotid, M1, or basilar arteries). Exploratory analyses were subsets with any occlusion and specific sites of occlusion (two-sided α = .01)., Results: Of 656 subjects, 306 (47%) underwent baseline CT angiography or magnetic resonance angiography. Of 306, 282 (92%) had arterial occlusions. At baseline CT angiography, proximal occlusions (n = 220) demonstrated no difference in primary outcome (41.3% [62 of 150] endovascular vs 38% [27 of 70] intravenous [IV] tissue-plasminogen activator [tPA]; relative risk, 1.07 [99% confidence interval: 0.67, 1.70]; P = .70); however, 24-hour recanalization rate was higher for endovascular treatment (n = 167; 84.3% [97 of 115] endovascular vs 56% [29 of 52] IV tPA; P < .001). Exploratory subgroup analysis for any occlusion at baseline CT angiography did not demonstrate significant differences between endovascular and IV tPA arms for primary outcome (44.7% [85 of 190] vs 38% [35 of 92], P = .29), although ordinal shift analysis of full mRS distribution demonstrated a trend toward more favorable outcome (P = .011). Carotid T- or L-type occlusion (terminal internal carotid artery [ICA] with M1 middle cerebral artery and/or A1 anterior cerebral artery involvement) or tandem (extracranial or intracranial) ICA and M1 occlusion subgroup also showed a trend favoring endovascular treatment over IV tPA alone for primary outcome (26% [12 of 46] vs 4% [one of 23], P = .047)., Conclusion: Significant differences were identified between treatment arms for 24-hour recanalization in proximal occlusions; carotid T- or L-type and tandem ICA and M1 occlusions showed greater recanalization and a trend toward better outcome with endovascular treatment. Vascular imaging should be mandated in future endovascular trials to identify such occlusions. Online supplemental material is available for this article., (© RSNA, 2014.)

Background and Purpose: The Capillary Index Score (CIS) is a simple angiography-based scale for assessing viable tissue in the ischemic territory. We retrospectively applied it to Interventional Management of Stroke (IMS) trials I and II to evaluate the predictive value for good outcomes., Methods: CIS was calculated from pretreatment diagnostic cerebral angiograms blinded to outcome. IMS I and II diagnostic cerebral angiogram images of sufficient quality were reviewed and CIS calculated for treated subjects with internal carotid artery or M1 occlusion. CIS scoring (0-3) was dichotomized into favorable (f CIS; 2 or 3) and poor (p CIS; 0 or 1). Modified thrombolysis in cerebral infarction score 2b or 3 was considered good revascularization. CIS and modified thrombolysis in cerebral infarction scores were compared with good outcome, defined as modified Rankin Scale score≤2 at 90 days., Results: Twenty-eight of 161 subjects met the inclusion criteria. Thirteen (46%) had f CIS. Good clinical outcome was significantly different between the 2 CIS groups (62% for f CIS versus 7% for p CIS; P=0.004). Good reperfusion correlated to good outcome (P=0.04). No significant differences in time to intravenous or intra-arterial treatment were identified between f CIS and p CIS groups (P>0.25)., Conclusions: A f CIS was found in ≈50% of subjects and was a virtual prerequisite for good outcome in this study subgroup of IMS I and II. We call this the 50% barrier., (© 2014 American Heart Association, Inc.)

Background: The IMS III trial did not show a clinical benefit of endovascular treatment compared with intravenous alteplase (recombinant tissue plasminogen activator) alone for moderate or severe ischaemic strokes. Late reperfusion of tissue that was no longer salvageable could be one explanation, as suggested by previous exploratory studies that showed an association between time to reperfusion and good clinical outcome. We sought to validate this association in a preplanned analysis of data from the IMS III trial., Methods: We used data for patients with complete proximal arterial occlusions in the anterior circulation who received endovascular treatment and achieved angiographic reperfusion (score on Thrombolysis in Cerebral Infarction scale of grade 2-3) during the endovascular procedure (within 7 h of symptom onset). We used logistic regression to model good clinical outcome (defined as a modified Rankin Scale score of 0-2 at 3 months) as a function of the time to reperfusion. We prespecified variables to be considered for adjustment, including age, baseline National Institutes of Health Stroke Scale score, sex, and baseline blood glucose concentration., Findings: Of 240 patients who were otherwise eligible for inclusion in our analysis, 182 (76%) achieved angiographic reperfusion. Mean time from symptom onset to reperfusion (ie, procedure end) was 325 min (SD 52). Increased time to reperfusion was associated with a decreased likelihood of good clinical outcome (unadjusted relative risk for every 30-min delay 0·85 [95% CI 0·77-0·94]; adjusted relative risk 0·88 [0·80-0·98])., Interpretation: Delays in time to angiographic reperfusion lead to a decreased likelihood of good clinical outcome in patients after moderate to severe stroke. Rapid reperfusion could be crucial for the success of future acute endovascular trials., Funding: US National Institutes of Health and National Institute of Neurological Disorders and Stroke., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background and Purpose: Endovascular strategies provide unique opportunity to correlate angiographic measures of collateral circulation at the time of endovascular therapy. We conducted systematic analyses of collaterals at conventional angiography on recanalization, reperfusion, and clinical outcomes in the endovascular treatment arm of the Interventional Management of Stroke (IMS) III trial., Methods: Prospective evaluation of angiographic collaterals was conducted via central review of subjects treated with endovascular therapy in IMS III (n=331). Collateral grade before endovascular therapy was assessed with the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology scale, blinded to all other data. Statistical analyses investigated the association between collaterals with baseline clinical variables, angiographic measures of recanalization, reperfusion and clinical outcomes., Results: Adequate views of collateral circulation to the ischemic territory were available in 276 of 331 (83%) subjects. Collateral grade was strongly related to both recanalization of the occluded arterial segment (P=0.0016) and downstream reperfusion (P<0.0001). Multivariable analyses confirmed that robust angiographic collateral grade was a significant predictor of good clinical outcome (modified Rankin Scale score≤2) at 90 days (P=0.0353), adjusted for age, history of diabetes mellitus, National Institutes of Health Stroke Scale strata, and Alberta Stroke Program Early CT Score. The relationship between collateral flow and clinical outcome may depend on the degree of reperfusion., Conclusions: More robust collateral grade was associated with better recanalization, reperfusion, and subsequent better clinical outcomes. These data, from the largest endovascular trial to date, suggest that collaterals are an important consideration in future trial design., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00359424.

Background and Purpose: The Interventional Management of Stroke (IMS)-III trial randomized patients with acute ischemic stroke to intravenous tissue-type plasminogen activator (tPA) plus endovascular therapy versus intravenous tPA therapy alone within 3 hours from symptom onset. A predefined secondary hypothesis was that subjects with significant early ischemic change on the baseline scan would not respond to endovascular therapy., Methods: The primary outcome was 90-day modified Rankin Scale score 0 to 2. The baseline and follow-up computed tomographic (CT) scan images were reviewed centrally and blinded to any clinical information. We assessed whether the baseline Alberta Stroke Program Early CT Score (ASPECTS) predicted outcome and interacted with study treatment. We analyzed subgroups defined by time from onset to intravenous tPA initiation and baseline occlusion status at a prespecified α=0.01., Results: Baseline demographic and clinical characteristics of 656 randomized patients were similar between subjects with a baseline ASPECTS 8 to 10 (58% of the study sample) versus 0 to 7. Subjects with ASPECTS 8 to 10 were almost twice as likely (relative risk, 1.8; 99% confidence interval, 1.4-2.4) to achieve a favorable outcome. There was insufficient evidence of a treatment-by-ASPECTS interaction. In those treated with onset to intravenous tPA <120 minutes, in CT angiography-proven internal carotid artery or middle cerebral artery occlusion, and in both, results were similar. The probability of achieving recanalization (arterial occlusion lesion, 2-3) of the primary arterial occlusive lesion (relative risk, 1.3; 99% confidence interval, 1.0-1.8) or achieving thrombolysis in cerebral ischemia score 2b/3 reperfusion (relative risk 2.0; 99% confidence interval, 1.2-3.2) was higher among subjects with higher ASPECTS., Conclusions: ASPECTS is a strong predictor of outcome and a predictor of reperfusion. ASPECTS did not identify a subpopulation of subjects that particularly benefitted from endovascular therapy immediately after routine intravenous tPA., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00359424.

Background and Purpose: In a previous study, 0.3 and 0.45 mg/kg of intravenous recombinant tissue plasminogen activator (rt-PA) were safe when combined with eptifibatide 75 mcg/kg bolus and a 2-hour infusion (0.75 mcg/kg per minute). The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER) trial sought to determine the safety of a higher-dose regimen and to establish evidence for a phase III trial., Methods: CLEAR-ER was a multicenter, double-blind, randomized safety study. Ischemic stroke patients were randomized to 0.6 mg/kg rt-PA plus eptifibatide (135 mcg/kg bolus and a 2-hour infusion at 0.75 mcg/kg per minute) versus standard rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracranial hemorrhage within 36 hours. The primary efficacy outcome measure was the modified Rankin Scale (mRS) score ≤1 or return to baseline mRS at 90 days. Analysis of the safety and efficacy outcomes was done with multiple logistic regression., Results: Of 126 subjects, 101 received combination therapy, and 25 received standard rt-PA. Two (2%) patients in the combination group and 3 (12%) in the standard group had symptomatic intracranial hemorrhage (odds ratio, 0.15; 95% confidence interval, 0.01-1.40; P=0.053). At 90 days, 49.5% of the combination group had mRS ≤1 or return to baseline mRS versus 36.0% in the standard group (odds ratio, 1.74; 95% confidence interval, 0.70-4.31; P=0.23). After adjusting for age, baseline National Institutes of Health Stroke Scale, time to intravenous rt-PA, and baseline mRS, the odds ratio was 1.38 (95% confidence interval, 0.51-3.76; P=0.52)., Conclusions: The combined regimen of intravenous rt-PA and eptifibatide studied in this trial was safe and provides evidence that a phase III trial is warranted to determine efficacy of the regimen., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00894803.

Background: Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic stroke, but whether a combined approach is more effective than intravenous t-PA alone is uncertain., Methods: We randomly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone, in a 2:1 ratio. The primary outcome measure was a modified Rankin scale score of 2 or less (indicating functional independence) at 90 days (scores range from 0 to 6, with higher scores indicating greater disability)., Results: The study was stopped early because of futility after 656 participants had undergone randomization (434 patients to endovascular therapy and 222 to intravenous t-PA alone). The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment (40.8% with endovascular therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage points; 95% confidence interval [CI], -6.1 to 9.1, with adjustment for the National Institutes of Health Stroke Scale [NIHSS] score [8-19, indicating moderately severe stroke, or ≥20, indicating severe stroke]), nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8 percentage points; 95% CI, -4.4 to 18.1) and those with a score of 19 or lower (-1.0 percentage point; 95% CI, -10.8 to 8.8). Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively; P=0.52) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P=0.83)., Conclusions: The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA, as compared with intravenous t-PA alone. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00359424.).

Background and Purpose: The role of endovascular therapy for acute M2 trunk occlusions is debatable. Through a subgroup analysis of Prolyse in Acute Cerebral Thromboembolism-II, we compared outcomes of M2 occlusions in treatment and control arms., Methods: Solitary M2 occlusions were identified from the Prolyse in Acute Cerebral Thromboembolism-II database. Primary endpoints were successful angiographic reperfusion (TICI 2-3) at 120 minutes and functional independence (mRS 0-2) at 90 days., Results: Forty-four patients with solitary M2 occlusions, 30 in the treatment arm and 14 in the control arm, were identified. Successful reperfusion (TICI 2-3) was achieved in 53.6% and 16.7% of patients in the treatment and control arms, respectively (P=0.04). A favorable clinical outcome (mRS 0-2) was observed in 53.3% and 28.6%, respectively (P=0.19). Baseline characteristics were similar between the 2 groups., Conclusions: Intra-arterial thrombolysis may lead to a 3-fold increase in the rate of early reperfusion of solitary M2 occlusions and could potentially double the chance of a favorable functional outcome at 90 days. Clinical Trial Registration- This trial was not registered because enrollment began before July 1, 2005.

Stroke is the third leading cause of death in the United States, Canada, Europe, and Japan. According to the American Heart Association and the American Stroke Association, there are now 750,000 new strokes that occur each year, resulting in 200,000 deaths, or 1 of every 16 deaths, per year in the United States alone. Endovascular therapy for patients with acute ischemic stroke is an area of intense investigation. The American Stroke Association has given a qualified endorsement of intra-arterial thrombolysis in selected patients. Intra-arterial thrombolysis has been studied in 2 randomized trials and numerous case series. Although 2 devices have been granted FDA phase 3 approval with an indication for mechanical stroke thrombectomy, none of these thrombectomy devices has demonstrated efficacy for the improvement of patient outcomes. The purpose of the present document is to define what constitutes adequate training to perform neuroendovascular procedures in patients with acute ischemic stroke and what performance standards should be adopted to assess outcomes. These guidelines have been written and approved by multiple neuroscience societies that historically have been directly involved in the medical, surgical and endovascular care of patients with acute stroke. These organizations include the Neurovascular Coalition and its participating societies, including the Society of NeuroInterventional Surgery (SNIS), American Academy of Neurology (AAN), American Association of Neurological Surgeons/Cerebrovascular Section (AANS/CNS), and Society of Vascular & Interventional Neurology (SVIN).

Stroke is the third leading cause of death in the USA, Canada, Europe, and Japan. According to the American Heart Association and the American Stroke Association, there are now 750,000 new strokes that occur each year, resulting in 200,000 deaths, or 1 of every 16 deaths, per year in the USA alone. Endovascular therapy for patients with acute ischemic stroke is an area of intense investigation. The American Stroke Association has given a qualified endorsement of intraarterial thrombolysis in selected patients. Intraarterial thrombolysis has been studied in two randomized trials and numerous case series. Although two devices have been granted FDA approval with an indication for mechanical stroke thrombectomy, none of these thrombectomy devices has demonstrated efficacy for the improvement of patient outcomes. The purpose of the present document is to define what constitutes adequate training to perform neuroendovascular procedures in patients with acute ischemic stroke and what performance standards should be adopted to assess outcomes. These guidelines have been written and approved by multiple neuroscience societies which historically have been directly involved in the medical, surgical and endovascular care of patients with acute stroke. The participating member organizations of the Neurovascular Coalition involved in the writing and endorsement of this document are the Society of NeuroInterventional Surgery, the American Academy of Neurology, the American Association of Neurological Surgeons/Congress of Neurological Surgeons Cerebrovascular Section, and the Society of Vascular & Interventional Neurology.

Background and Purpose: The occurrence of brain parenchymal signal-intensity changes within the drainage territory of developmental venous anomalies (DVAs) in the absence of cavernous malformations (CMs) has been incompletely assessed. This study was performed to evaluate the prevalence of brain parenchymal signal-intensity abnormalities subjacent to DVA, correlating with DVA morphology and location., Materials and Methods: One hundred sixty-four patients with brain MR imaging with contrast studies performed from July 2005 through June 2006 formed the study group. The examinations were reviewed and data were collected regarding the following: location, depth, size of draining vein, associated increased signal intensity on fluid-attenuated inversion recovery and T2-weighted images, associated CMs, and associated signal intensity on gradient recalled-echo sequences., Results: Of the 175 DVAs identified, 28 had associated signal-intensity abnormalities in the drainage territory. Seven of 28 DVAs with signal-intensity abnormalities were excluded because of significant adjacent white matter signal-intensity changes related to other pathology overlapping the drainage territory. Of the remaining DVAs imaged in this study, 21/168 (12.5%) had subjacent signal-intensity abnormalities. An adjusted prevalence rate of 9/115 (7.8%) was obtained by excluding patients with white matter disease more than minimal in degree. Periventricular location and older age were associated with DVA signal-intensity abnormality., Conclusion: Signal-intensity abnormalities detectable by standard clinical MR images were identified in association with 12.5% of consecutively identified DVAs. Excluding patients with significant underlying white matter disease, we adjusted the prevalence to 7.8%. The etiology of the signal-intensity changes is unclear but may be related to edema, gliosis, or leukoaraiosis secondary to altered hemodynamics in the drainage area.

Background and Purpose: Large arachnoid granulations (AG) within the dorsal superior sagittal sinus (SSS) have been incompletely characterized and can be confused with pathology. This report reviews the characteristics of these anatomic structures to establish common imaging features that allow differentiation from pathology., Materials and Methods: Twelve cases of large AG in the dorsal SSS are presented, identified by MR imaging. Signal intensity characteristics, size, location, venographic appearance, and association with adjacent venous and osseous structures were documented., Results: A defect in the dura of the SSS was seen in all of the cases communicating with the subjacent subarachnoid space. The average size of the AG was 8.1 x 9.4 x 10.0 mm (range, 4-19 mm). Ten produced calvarial remodeling, and 11 were in the direct vicinity of the lambda. On T2-weighted images, all were hyperintense to the brain. On T1-weighted images, 8 were hypointense and 4 were hypointense with mixed areas of isointense signal intensity. All of the AGs were associated with cortical venous structures entering the sinus. On MR venography, AGs appeared as focal protrusions into the sinus, displacing, distorting, and narrowing the sinus lumen. Seven patients had headache without other visible cause on MR imaging, and 4 were initially interpreted as thrombosis or tumor., Conclusion: Large AGs can occur in the dorsal SSS. They are well-defined projections of the subarachnoid space into the sinus, can cause luminal narrowing and calvarial remodeling, and have typical signal intensity characteristics, position, and morphology differentiating them from other pathology. Association with patient symptoms is uncertain.