Anterior Circulation Proximal Occlusion Research Articles

Dynamic Magnetic Resonance Angiography Provides Collateral Circulation and Hemodynamic Information in Acute Ischemic Stroke.

Contrary to usual static vascular imaging techniques, contrast-enhanced dynamic magnetic resonance angiography (dMRA) enables dynamic study of cerebral vessels. We evaluated dMRA ability to assess arterial occlusion, cerebral hemodynamics, and collateral circulation in acute ischemic stroke. Twenty-five acute ischemic stroke patients with proximal anterior circulation occlusion underwent dMRA on a 3T scanner within 12 hours of symptoms onset. Diffusion weighted imaging, Tmax6 s lesion volumes and hypoperfusion intensity ratio as volume of Tmax>6 s/volume of Tmax>10 s were measured. Site and grade of occlusion (Thrombolysis in Myocardial Infarction criteria) were evaluated on time-of-flight MRA and dMRA. Leptomeningeal collaterality (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology [ASITN/SIR] Scale) and asymmetries in venous clearance were assessed exclusively on dMRA. Collateral filling was dichotomized into incomplete (ASITN/SIR 0-2) or complete (ASITN/SIR 3-4). On dMRA, site of occlusion was M1 in 21 patients, tandem internal carotid artery/M1 in 2 and tandem internal carotid artery/terminal internal carotid artery in 2 patients. Three tandem occlusions were not detected on time-of-flight-MRA. All patients had Thrombolysis in Myocardial Infarction 0 to 1 on time-of-flight-MRA, but three of them had Thrombolysis in Myocardial Infarction 2 on dMRA. Complete collateral filling (n=12, 48%) was associated with smaller diffusion weighted imaging lesion volume (P=0.039), smaller hypoperfused volume (P=0.018), and lower hypoperfusion intensity ratio (P=0.006). Patients with symmetrical clearance of transverse sinuses (52%) were more likely to have complete collateral filling (P=0.015). As a fast, direct, feasible, noninvasive, and reliable method to assess site of occlusion, collateral circulation and hemodynamic alterations, dMRA provides profound insights in acute stroke.

Reperfusion Strategies for Acute Ischaemic Stroke From Past to Present: An Overview Towards Future Perspectives

Timely reperfusion of brain ischaemic tissue is the main therapeutic target for acute stroke. In the last few decades many recanalisation strategies have been studied by randomised controlled trials (RCTs), including intravenous (IV), intra-arterial (IA), and combined approaches. Clinical research is addressed to identify the drug associated with the better reperfusion properties and the lower rate of side-effects. To date, according to current evidence-based guidelines, IV tissue plasminogen activator (tPA) is the only approved treatment for acute ischaemic stroke (AIS) within 4.5 hours from onset. Other IV thrombolytics, such as tenecteplase and desmoteplase, have shown promising results in preliminary RCTs and are currently being investigated to produce further evidence. Endovascular catheter-based treatments (including IA administration of thrombolytics or mechanical thrombectomy) have quite inferior feasibility, being performed only by stroke-trained interventional neuroradiologists. Until a few months ago, many trials had investigated the safety and efficacy of endovascular techniques compared with IV tPA without consistent results, limiting their application to patients with contraindications or poor response to IV tPA. More recently, the Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN), Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing CT to recanalization times (ESCAPE), and Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-arterial (EXTEND-IA) trial results have demonstrated the superiority of endovascular procedures associated with standard care in AIS due to proximal arterial occlusion in the anterior cerebral circulation. These data are going to change the current decision-making process and the care pathway in AIS patients.

Multivariate dynamic prediction of ischemic infarction and tissue salvage as a function of time and degree of recanalization.

Benefit of endovascular recanalization beyond established treatment time windows likely exists in select stroke patients. However, there is currently no imaging model that predicts infarction adjusting for elapsed time between the pathologic snapshot of admission imaging until endovascular recanalization. We trained and cross validated a multivariate generalized linear model (GLM) that uses computer tomography perfusion and clinical data to quantify patient-specific dynamic change of tissue infarction depending on degree and time of recanalization. Multicenter data of 161 patients with proximal anterior circulation occlusion undergoing endovascular therapy were included. Multivariate voxelwise infarct probability was calculated within the GLM. The effect of increasing time to treatment and degree of recanalization on voxelwise infarction was calculated in each patient. Tissue benefit of successful relative to unsuccessful recanalization was shown up to 15 hours after onset in individual patients and decreased nonlinearly with time. On average, the relative reduction of infarct volume at the treatment interval of 5 hours was 53% and this salvage effect decreased by 5% units per hour to <5% after 10 additional hours to treatment. Treatment time-adjusted multivariate prediction of infarction by perfusion and clinical status may identify patients who benefit from extended time to recanalization therapy.

Thrombectomy within 8 Hours after Symptom Onset in Ischemic Stroke

BackgroundWe aimed to assess the safety and efficacy of thrombectomy for the treatment of stroke in a trial embedded within a population-based stroke reperfusion registry.MethodsDuring a 2-year period at four centers in Catalonia, Spain, we randomly assigned 206 patients who could be treated within 8 hours after the onset of symptoms of acute ischemic stroke to receive either medical therapy (including intravenous alteplase when eligible) and endovascular therapy with the Solitaire stent retriever (thrombectomy group) or medical therapy alone (control group). All patients had confirmed proximal anterior circulation occlusion and the absence of a large infarct on neuroimaging. In all study patients, the use of alteplase either did not achieve revascularization or was contraindicated. The primary outcome was the severity of global disability at 90 days, as measured on the modified Rankin scale (ranging from 0 [no symptoms] to 6 [death]). Although the maximum planned sample size was 690, enrollment was halted early because of loss of equipoise after positive results for thrombectomy were reported from other similar trials.ResultsThrombectomy reduced the severity of disability over the range of the modified Rankin scale (adjusted odds ratio for improvement of 1 point, 1.7; 95% confidence interval [CI], 1.05 to 2.8) and led to higher rates of functional independence (a score of 0 to 2) at 90 days (43.7% vs. 28.2%; adjusted odds ratio, 2.1; 95% CI, 1.1 to 4.0). At 90 days, the rates of symptomatic intracranial hemorrhage were 1.9% in both the thrombectomy group and the control group (P=1.00), and rates of death were 18.4% and 15.5%, respectively (P=0.60). Registry data indicated that only eight patients who met the eligibility criteria were treated outside the trial at participating hospitals.ConclusionsAmong patients with anterior circulation stroke who could be treated within 8 hours after symptom onset, stent retriever thrombectomy reduced the severity of post-stroke disability and increased the rate of functional independence. (Funded by Fundació Ictus Malaltia Vascular through an unrestricted grant from Covidien and others; REVASCAT ClinicalTrials.gov number, NCT01692379.)

Stroke Neurologist's Perspective on the New Endovascular Trials.

Before December 2014, the only proven effective treatment for acute ischemic stroke was recombinant tissue-type plasminogen activator (r-tPA). This has now changed with the publication of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits--Intra-Arterial (EXTEND IA), Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment Trial (SWIFT PRIME), and Randomized Trial of Revascularization With the Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT) studies. We review the main results of these studies and how they inform stroke patient management going forward. The main take home points for neurologists are (1) intra-arterial thrombectomy is a potently effective treatment and should be offered to patients who have documented occlusion in the distal internal carotid or the proximal middle cerebral artery, have a relatively normal noncontrast head computed tomographic scan, severe neurological deficit, and can have intra-arterial thrombectomy within 6 hours of last seen normal; (2) benefits are clear in patients receiving r-tPA before intra-arterial thrombectomy; r-tPA should not be withheld if the patient meets criteria, and benefit in patients who do not receive r-tPA or have r-tPA exclusions requires further study; and (3) these favorable results occur when intra-arterial thrombectomy is performed in an endovascular stroke center by a coordinated multidisciplinary team that extends from the prehospital stage to the endovascular suite, minimizes time to recanalization, uses stent-retriever devices, and avoids general anesthesia. In conclusion, stroke teams, including practicing neurologists caring for patients with stroke should now provide the option for intra-arterial thrombectomy for a subset of patients with acute stroke.

Dawning of a new era for acute stroke therapy.

The results of the 4 recently presented/published trials for acute ischemic stroke herald the dawn of a new era in the treatment of patients with large vessel occlusion amenable to endovascular intervention. Additional trials are underway or have been stopped earlier because of the positive results observed in the initial trials. Hopefully, the ongoing trials will largely amplify and build on the results observed in the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic in the Netherlands (MR CLEAN), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA) and Solitaire With the Intention for Thrombectomy as Primary Endovascular Treament (SWIFT-PRIME) trials. At this time, it is important for the medical community, healthcare planners, and policy makers to have interpretation and guidance from experts about the trial results currently available for help in steering them as to how the trial results should be used in daily practice and for the local organization of acute stroke care. To accomplish this goal, …

Role of imaging in current acute ischemic stroke workflow for endovascular therapy.

Ischemic stroke is caused by a thrombus that blocks an intracranial artery. Brain tissue beyond the blocked artery survives for a variable period of time because of blood and nutrients received through tiny vessels called collaterals. Imaging the brain and the vasculature that supplies it is therefore a vital first step in treating patients with acute ischemic stroke. In this review, we focus on current evidence for imaging selection of patients for endovascular therapy in the context of the recently positive clinical trials, such as Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing Computed Tomography to Recanalization Times (ESCAPE), Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), and Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA). We discuss evidence for and use of the various imaging paradigms available. We discuss how to set up quick and efficient imaging protocols for patient selection and address common concerns about the use of imaging, including time spent, contrast, radiation, and other advantages and disadvantages. Finally, we briefly comment on how imaging can integrate itself within various health systems of care in the future, thereby potentially improving patient outcomes further.

American Stroke Association Stroke Council Update

This report represents the Spring 2015 update of the Stroke Council. Much has happened in the last 12 months, and we want to particularly focus on the major developments in acute stroke therapy and their implications, progress in the American Stroke Association (ASA)/American Heart Association (AHA) quality initiatives and tiered systems of stroke care, and the approval of a new code for the National Institutes of Health Stroke Scale (NIHSS). Each Stroke Council Update starts with restating our 2020 Goals: to improve the cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular diseases and stroke by 20%. In December 2014, we had further evidence that our efforts are bearing fruits. In 2011, stroke fell from the number 3 to the number 4 cause of death in the United States, and in December, stroke fell from number 4 to number 5. This development, which reflects the continued decrease in age-adjusted mortality rates for stroke, is a remarkable testament to concerted educational and public health efforts to control blood pressure, decrease tobacco use, appropriately treat atrial fibrillation, educate the public about stroke warning signs, and improve and standardize the neurocritical care of stroke patients. Yet, it is sobering that the actual number of strokes continues to increase as the population ages because the incidence of stroke increases markedly with age. Stroke remains the second leading cause of death worldwide and one of the leading causes of disability worldwide. That is why the ASA/AHA is partnering with the World Stroke Organization and World Health Organization to take best practices and apply them worldwide. We have accomplished much but have more to do. The International Stroke Conference Scientific Sessions and Pre-conference meetings in Nashville was a great success with 4341 attendees, the largest number of attendees ever. The quality of the …

Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing CT to recanalization times (ESCAPE) trial: methodology.

ESCAPE is a prospective, multicenter, randomized clinical trial that will enroll subjects with the following main inclusion criteria: less than 12 h from symptom onset, age > 18, baseline NIHSS >5, ASPECTS score of >5 and CTA evidence of carotid T/L or M1 segment MCA occlusion, and at least moderate collaterals by CTA. The trial will determine if endovascular treatment will result in higher rates of favorable outcome compared with standard medical therapy alone. Patient populations that are eligible include those receiving IV tPA, tPA ineligible and unwitnessed onset or wake up strokes with 12 h of last seen normal. The primary end-point, based on intention-to-treat criteria is the distribution of modified Rankin Scale scores at 90 days assessed using a proportional odds model. The projected maximum sample size is 500 subjects. Randomization is stratified under a minimization process using age, gender, baseline NIHSS, baseline ASPECTS (8-10 vs. 6-7), IV tPA treatment and occlusion location (ICA vs. MCA) as covariates. The study will have one formal interim analysis after 300 subjects have been accrued. Secondary end-points at 90 days include the following: mRS 0-1; mRS 0-2; Barthel 95-100, EuroQOL and a cognitive battery. Safety outcomes are symptomatic ICH, major bleeding, contrast nephropathy, total radiation dose, malignant MCA infarction, hemicraniectomy and mortality at 90 days.

Prediction of infarction and reperfusion in stroke by flow- and volume-weighted collateral signal in MR angiography.

In proximal anterior circulation occlusive strokes, collateral flow is essential for good outcome. Collateralized vessel intensity in TOF- and contrast-enhanced MRA is variable due to different acquisition methods. Our purpose was to quantify collateral supply by using flow-weighted signal in TOF-MRA and blood volume-weighted signal in contrast-enhanced MRA to determine each predictive contribution to tissue infarction and reperfusion. Consecutively (2009-2013), 44 stroke patients with acute proximal anterior circulation occlusion met the inclusion criteria with TOF- and contrast-enhanced MRA and penumbral imaging. Collateralized vessels in the ischemic hemisphere were assessed by TOF- and contrast-enhanced MRA using 2 methods: 1) visual 3-point collateral scoring, and 2) collateral signal quantification by an arterial atlas-based collateral index. Collateral measures were tested by receiver operating characteristic curve and logistic regression against 2 imaging end points of tissue-outcome: final infarct volume and percentage of penumbra saved. Visual collateral scores on contrast-enhanced MRA but not TOF were significantly higher in patients with good outcome. Visual collateral scoring on contrast-enhanced MRA was the best rater-based discriminator for final infarct volume < 90 mL (area under the curve, 0.81; P < .01) and percentage of penumbra saved >50% (area under the curve, 0.67; P = .04). Atlas-based collateral index of contrast-enhanced MRA was the overall best independent discriminator for final infarct volume of <90 mL (area under the curve, 0.94; P < .01). Atlas-based collateral index combining the signal of TOF- and contrast-enhanced MRA was the overall best discriminator for effective reperfusion (percentage of penumbra saved >50%; area under the curve, 0.89; P < .001). Visual scoring of contrast-enhanced but not TOF-MRA is a reliable predictor of infarct outcome in stroke patients with proximal arterial occlusion. By atlas-based collateral assessment, TOF- and contrast-enhanced MRA both contain predictive signal information for penumbral reperfusion. This could improve risk stratification in further studies.

Percentage insula ribbon infarction of >50% identifies patients likely to have poor clinical outcome despite small DWI infarct volume.

Large admission DWI infarct volume (>70 mL) is an established marker for poor clinical outcome in acute stroke. Outcome is more variable in patients with small infarcts (<70 mL). Percentage insula ribbon infarct correlates with infarct growth. We hypothesized that percentage insula ribbon infarct can help identify patients with stroke likely to have poor clinical outcome, despite small admission DWI lesion volumes. We analyzed the admission NCCT, CTP, and DWI scans of 55 patients with proximal anterior circulation occlusions on CTA. Percentage insula ribbon infarct (>50%, ≤50%) on DWI, NCCT, CT-CBF, and CT-MTT were recorded. DWI infarct volume, percentage DWI motor strip infarct, NCCT-ASPECTS, and CTA collateral score were also recorded. Statistical analyses were performed to determine accuracy in predicting poor outcome (mRS >2 at 90 days). Admission DWI of >70 mL and DWI-percentage insula ribbon infarct of >50% were among significant univariate imaging markers of poor outcome (P < .001). In the multivariate analysis, DWI-percentage insula ribbon infarct of >50% (P = .045) and NIHSS score (P < .001) were the only independent predictors of poor outcome. In the subgroup with admission DWI infarct of <70 mL (n = 40), 90-day mRS was significantly worse in those with DWI-percentage insula ribbon infarct of >50% (n = 9, median mRS = 5, interquartile range = 2-5) compared with those with DWI-percentage insula ribbon infarct of ≤50% (n = 31, median mRS = 2, interquartile range = 0.25-4, P = .036). In patients with admission DWI infarct of >70 mL, DWI-percentage insula ribbon infarct did not have added predictive value for poor outcome (P = .931). DWI-percentage insula ribbon infarct of >50% independently predicts poor clinical outcome and can help identify patients with stroke likely to have poor outcome despite small admission DWI lesion volumes.

Early reperfusion rates with IV tPA are determined by CTA clot characteristics.

An ability to predict early reperfusion with IV tPA in patients with acute ischemic stroke and intracranial clots can help clinicians decide if additional intra-arterial therapy is needed or not. We explored the association between novel clot characteristics on baseline CTA and early reperfusion with IV tPA in patients with acute ischemic stroke by using classification and regression tree analysis. Data are from patients with acute ischemic stroke and proximal anterior circulation occlusions from the Calgary CTA data base (2003-2012) and the Keimyung Stroke Registry (2005-2009). Patients receiving IV tPA followed by intra-arterial therapy were included. Clot location, length, residual flow within the clot, ratio of contrast Hounsfield units pre- and postclot, and the M1 segment origin to the proximal clot interface distance were assessed on baseline CTA. Early reperfusion (TICI 2a and above) with IV tPA was assessed on the first angiogram. Two hundred twenty-eight patients (50.4% men; median age, 69 years; median baseline NIHSS score, 17) fulfilled the inclusion criteria. Median symptom onset to IV tPA time was 120 minutes (interquartile range = 70 minutes); median IV tPA to first angiography time was 70.5 minutes (interquartile range = 62 minutes). Patients with residual flow within the clot were 5 times more likely to reperfuse than those without it. Patients with residual flow and a shorter clot length (≤15 mm) were most likely to reperfuse (70.6%). Patients with clots in the M1 MCA without residual flow reperfused more if clots were distal and had a clot interface ratio in Hounsfield units of <2 (36.8%). Patients with proximal M1 clots without residual flow reperfused 8% of the time. Carotid-T/-L occlusions rarely reperfused (1.7%). Interrater reliability for these clot characteristics was good. Our study shows that clot characteristics on CTA help physicians estimate a range of early reperfusion rates with IV tPA.

Impact of Pretreatment Noncontrast CT Alberta Stroke Program Early CT Score on Clinical Outcome After Intra-Arterial Stroke Therapy

The efficacy of intra-arterial treatment remains uncertain. Because most centers performing IAT use noncontrast CT (NCCT) imaging, it is critical to understand the impact of NCCT findings on treatment outcomes. This study aimed to compare functional independence and safety among patients undergoing intra-arterial treatment stratified by the extent of ischemic change on pretreatment NCCT. The study cohort was derived from multicenter trials of the Penumbra System. Inclusion criteria were anterior circulation proximal occlusion, evaluable pretreatment NCCT, and known time to reperfusion. Ischemic change was quantified using the Alberta Stroke Program Early CT Score (ASPECTS) and stratified into 3 prespecified groups for comparison: 0 to 4 (most ischemic change) versus 5 to 7 versus 8 to 10 (least ischemic change). A total of 249 patients were analyzed: 40 with ASPECTS 0 to 4, 83 with ASPECTS 5 to 7, and 126 with ASPECTS 8 to 10. For ASPECTS 0 to 4, 5 to 7, and 8 to 10, respectively, good outcome (modified Rankin Scale score, 0-2) rates were 5%, 38.6%, and 46% (P<0.0001), and mortality rates were 55%, 28.9%, and 19% (P=0.0001). The only significant pairwise differences were between ASPECTS 0 to 4 and other groups. Symptomatic hemorrhage was more common with lower ASPECTS (P=0.02). Shorter time to reperfusion was significantly associated with better outcomes among patients with ASPECTS 8 to 10 (P=0.01). A similar relationship was seen for ASPECTS 5 to 7 but was not statistically significant. No such relationship was seen for ASPECTS 0 to 4. NCCT seems useful for excluding patients with the greatest burden of ischemic damage from futile intra-arterial treatment, which is unlikely to result in patient functional independence and increases the risk of hemorrhage.

Abstract W P43: Clot Characteristics on Ct-angiography Predict Early Recanalization With Intravenous Tpa in Patients With Acute Ischemic Stroke

Objective: We explore relationships amongst known and novel clot characteristics identified on CTA and early recanalization with IV tPA using classification and regression tree analysis (CART). Methods: Data is from patients presenting with acute ischemic stroke and proximal anterior circulation occlusions from the Calgary CTA database (2003-2012) and the Keimyung Stroke Registry (2005-2009). Patients who received IV t-PA followed by endovascular therapy were included. Clot location, clot length, residual flow through clot, ratio of contrast HU pre/post clot (cirHU) and distance of clot from M1 origin (for M1 MCA occlusions), were assessed on baseline CT-angio using OsiriX (Fig 1). Early recanalization (TICI 2a, 2b &amp; 3) with IV t-PA was assessed on DSA first run. Results: We identified 228 patients (50.4% male, median age 69 yrs, median baseline NIHSS 17) who fulfilled inclusion criteria. Median symptom onset to IV t-PA time was 120 mins (IQR=70 mins) and median IV t-PA bolus to first angio run time was 70.5 mins (IQR=62 mins). Patients with residual flow within clot are five times more likely to recanalize than those without. Patients with residual flow within clot and a shorter clot length (≤15mm) were the most likely to recanalize(70.6%). Patients without residual flow with a carotid T/L occlusion rarely recanalized (1.7%). Patients without residual flow in M1 clots recanalized more if they were distal and had a cirHU &lt; 2 (36.8%). (Fig 2). Inter-rater reliability for these clot characteristics was good to excellent. Conclusion: Clot characteristics on CTA could help physicians estimate early recanalization rates with IV tPA for proximal clots ranging from 0% to more than 80%.

Prognosis of Untreated Strokes Due to Anterior Circulation Proximal Intracranial Arterial Occlusions Detected by Use of Computed Tomography Angiography

Limited data exist regarding the natural history of proximal intracranial arterial occlusions. OBJECTIVE To investigate the outcomes of patients who had an acute ischemic stroke attributed to an anterior circulation proximal intracranial arterial occlusion. A prospective cohort study at 2 university-based hospitals from 2003 to 2005 in which nonenhanced computed tomography scans and computed tomography angiograms were obtained at admission of all adult patients suspected of having an ischemic stroke in the first 24 hours of symptom onset. Anterior circulation proximal intracranial arterial occlusion. Frequency of good outcome (defined as a modified Rankin Scale score of ≤ 2) and mortality at 6 months. A total of 126 patients with a unilateral complete occlusion of the intracranial internal carotid artery (ICA; 26 patients: median National Institutes of Health Stroke Scale [NIHSS] score, 11 [interquartile range, 5-17]), of the M1 segment of the middle cerebral artery (MCA; 52 patients: median NIHSS score, 13 [interquartile range, 6-16]), or of the M2 segment of the MCA (48 patients: median NIHSS score, 7 [interquartile range, 4-15]) were included. Of these 3 groups of patients, 10 (38.5%), 20 (38.5%), and 26 (54.2%) with ICA, MCA-M1, and MCA-M2 occlusions, respectively, achieved a modified Rankin Scale score of 2 or less, and 6 (23.1%), 12 (23.1%), and 10 (20.8%) were dead at 6 months. Worse outcomes were seen in patients with a baseline NIHSS score of 10 or higher, with a modified Rankin Scale score of 2 or less achieved in only 7.1% (1 of 14), 23.5% (8 of 34), and 22.7% (5 of 22) of patients and mortality rates of 35.7% (5 of 14), 32.4% (11 of 34), and 40.9% (9 of 22) among patients with ICA, MCA-M1, and MCA-M2 occlusions, respectively. Age (odds ratio, 0.94 [95% CI, 0.91-0.98]), NIHSS score (odds ratio, 0.73 [95% CI, 0.64-0.83]), and strength of leptomeningeal collaterals (odds ratio, 2.37 [95% CI, 1.08-5.20]) were independently associated with outcome, whereas the level of proximal intracranial arterial occlusion (ICA vs MCA-M1 vs MCA-M2) was not. The natural history of proximal intracranial arterial occlusion is variable, with poor outcomes overall. Stroke severity and collateral flow appear to be more important than the level of proximal intracranial arterial occlusion in determining outcomes. Our results provide useful data for proper patient selection and sample size calculations in the design of new clinical trials aimed at recanalization therapies.

Inter- and Intraobserver Agreement in Scoring Angiographic Results of Intra-Arterial Stroke Therapy

Angiographic results are commonly used as surrogate markers of the success of intra-arterial therapies for acute stroke. Inter- and intraobserver agreement in judging angiographic results remain poorly characterized. Our goal was to assess 2 commonly used revascularization scales. A portfolio of 148 pre- and post treatment images of 37 cases of proximal anterior circulation occlusions was electronically sent to 12 expert observers who were asked to grade treatment outcomes according to recanalization (of arterial occlusive lesion) or reperfusion (TICI) scales. Three expert observers had to score treatment outcomes by using a similar portfolio of 32 patients or when they had full access to all angiographic data, twice for each method 3-12 months apart. Results were analyzed by using κ statistics. Agreement among 9 responding observers was moderate for both the TICI (κ = 0.45 ± 0.01) and arterial occlusive lesion (κ = 0.39 ± 0.16) scales. Agreement was similar (moderate) when 3 observers had access to a portfolio (κ = 0.59 ± 0.06 and 0.49 ± 0.07, respectively) or to the full angiographic data (κ = 0.54 ± 0.06 and 0.59 ± 0.07, respectively). Intraobserver agreement was "fair to moderate" for both methods. Interobserver agreement became "substantial" (>0.6) when outcomes were dichotomized into "success" (TICI 2b, 3; arterial occlusive lesion II, III or "failure"; the results were judged more favorably when the arterial occlusive lesion rather than the TICI scale was used. There is an important variability in the assessment of angiographic outcomes of endovascular treatments, invalidating comparisons among publications. A simple dichotomous judgment can be used as a surrogate outcome when treatments are assessed by the same observers in randomized trials.

Clot Length Distribution and Predictors in Anterior Circulation Stroke

Background and Purpose— Thin-section noncontrast computed tomography images can be used to measure hyperdense clot length in acute ischemic stroke. Clots ≥8 mm have a very low probability of intravenous tissue-type plasminogen activator recanalization and hence may benefit from a bridging intra-arterial approach. To understand the prevalence of such clots, we sought to determine the distribution and predictors of clot lengths in consecutive anterior circulation proximal artery occlusions. Methods— Of 623 consecutive patients with acute ischemic stroke, 53 met inclusion criteria: presentation &lt;8 hours from onset; intracranial internal carotid artery-terminus or proximal-middle cerebral artery occlusion; admission thin-slice noncontrast computed tomography (≤2.5 mm); and no intravenous tissue-type plasminogen activator pretreatment. For each patient, hyperdense clot length was measured and recorded along with additional relevant imaging and clinical data. Results— Mean age was 70 years, and mean time to computed tomography was 213 minutes. Median baseline National Institutes of Health Stroke Scale was 16.5. Occlusions were located in the internal carotid artery-terminus (34% [18 of 53]), middle cerebral artery M1 (49% [26 of 53]) and M2 segments (17% [9 of 53]). Hyperdense thrombus was visible in 96%, with mean and median clot lengths (mm) of 18.5 (±14.2) and 16.1 (7.6–25.2), respectively. Occlusion location was the strongest predictor of clot length (multivariate, P =0.02). Clot length was ≥8 mm in 94%, 73%, and 22% of internal carotid artery-terminus, M1, and M2 occlusions, respectively. Conclusions— The majority of anterior circulation proximal occlusions are ≥8 mm long, helping to explain the low published rates of intravenous tissue-type plasminogen activator recanalization. Internal carotid artery-terminus occlusion is an excellent marker for clot length ≥8 mm; vessel-imaging status alone may be sufficient. Thin-section noncontrast computed tomography seems useful for patients with middle cerebral artery occlusion because of the wide variability of clot lengths.

Time Dependence of Reliability of Noncontrast Computed Tomography in Comparison to Computed Tomography Angiography Source Image in Acute Ischemic Stroke

There is no consensus on how the reliability and predictive ability of noncontrast computed tomography (NCCT) and computed tomography angiography source image (CTASI) change over time from acute ischemic stroke onset. We hypothesized that the reliability for detecting early ischemic changes (EIC) would be lower in early time periods and that changes identified on CTASI would be more reliable across examiners than changes identified on NCCT. To address this, we compared the relationships between CTASI, NCCT, and final infarct in patients with initial computed tomography (CT) imaging at different time points after stroke onset. Patients with acute ischemic stroke with proximal anterior circulation occlusions (internal carotid artery, middle carotid artery M1, proximal M2) from Calgary CT Angiography (CTA) database were studied. The cohort was categorized in four groups based on time from stroke onset to baseline NCCT/CTA: 0-90 mins (n = 69), 91-180 mins (n = 88), 181-360 mins (n = 46), and >360 mins (n = 58). Median scores of NCCT-Alberta Stroke Program Early CT Score (ASPECTS), CTASI ASPECTS, and follow-up ASPECTS among different time categories were compared. To determine reliability, a subsample of NCCT brain and CTASI were interpreted at separate sessions weeks apart by two neuroradiologists and two stroke neurologists in random order. Median and mean ASPECTS ratings on NCCT and CTASI were higher than final ASPECTS in each time category (P < 0·001 for all comparisons). CTASI ASPECTS was lower than NCCT ASPECTS in each time category, and differences were significant at 0-90 mins and 91-180 mins (P < 0·001). The least agreement among readers was in detection of EIC on NCCT brain in the ultra-early phase (<90 mins) [intraclass correlation coefficient (ICC) = 0·48. By contrast, there was excellent agreement on EIC on CTASI regardless of time period (ICC = 0·87-0·96). Using ASPECTS methodology, CTASI is more reliable than NCCT at predicting final infarct extent particularly in the early time windows.

Infarct Volume Is a Pivotal Biomarker After Intra-Arterial Stroke Therapy

Pretreatment infarct volume appears to predict clinical outcome after intra-arterial therapy. To confirm the importance of infarct size in patients undergoing intra-arterial therapy, we sought to characterize the relationship between final infarct volume (FIV) and long-term functional outcome in a prospective cohort of endovascularly treated patients. From our prospective intra-arterial therapy database, we identified 107 patients with acute ischemic stroke with anterior circulation proximal artery occlusions who underwent final infarct imaging and had 3-month modified Rankin Scale scores. Clinical, imaging, treatment, and outcome data were analyzed. Mean age was 66.6 years. Median admission National Institutes of Health Stroke Scale score was 17. Reperfusion (Thrombolysis In Cerebral Infarction 2A-3) was achieved in 78 (72.9%) patients. Twenty-seven (25.2%) patients achieved a 3-month good outcome (modified Rankin Scale 0-2), and 30 (28.0%) died. Median FIV was 71.4 cm(3). FIV independently correlated with functional outcome across the entire modified Rankin Scale. In receiver operating characteristic analysis, it was the best discriminator of both good outcome (area under the curve=0.857) and mortality (area under the curve=0.772). A FIV of approximately 50 cm(3) demonstrated the greatest accuracy for distinguishing good versus poor outcome, and a FIV of approximately 90 cm(3) was highly specific for a poor outcome. The interaction term between FIV and age was the only independent predictor of good outcome (P<0.0001). The impact of FIV was accentuated in patients <80 years. Among patients with anterior circulation acute ischemic stroke who undergo intra-arterial therapy, final infarct volume is a critical determinant of 3-month functional outcome and appears suitable as a surrogate biomarker in proof-of-concept intra-arterial therapy trials.

Abstract 3968: Eloquence Of Region And Extent Of Brain Ischemia Detected By DWI Predicts Degree Of 24h Nihss Score Improvement After Arterial Recanalization In Ischemic Stroke

Introduction Improvement in NIHSS score at 24 hrs or delta NIHSS change (ΔNIHSS) is an early measure of response to recanalization treatment and has been associated with good outcome. We hypothesized that ΔNIHSS achieved with arterial recanalization may be influenced by eloquence of region involved within a vascular territory on baseline imaging. Methods Patients from prospectively collected Keimyung University stroke database, [2005-2009] were analyzed. Patients with proximal anterior circulation occlusions (ICA, MCA M1, proximal M2) who recanalized after IV tPA/IV tPA+endovascular therapy (TIMI 2/3) on DSA / MRA were included for final analysis.Detailed clinical and biochemical data collected prospectively was analyzed. Imaging analysis was done in University of Calgary. Two readers evaluated baseline DWI imaging and graded ischemic infarcts in16 anatomical regions(cortical MCA-M1,M2,M3,M4,M5,M6, insula; subcortical MCA- corona radiata -C1,C2,C3, basal ganglia; posterior limb of internal capsule; ACA- A1,A2 and PCA-P1,P2). Depending on the number of infarct regions involved, patients were categorized into three groups: mild - (0-3 infarct regions), moderate-(4-6), large and extensive (7-16). Improvement of 10 point in NIHSS score was labeled as treatment responders. ΔNIHSS change per point was the primary outcome. Results Among 265 patients in database, 101 patients who recanalized (TIMI2/3,) were analyzed. ΔNIHSS ≥10 was seen in 24 (24%) of subjects. There were 56% males. The mean age of patients was 65+-11.2yrs, Baseline median NIHSS was: 14 (IQR -11-16) and 24 hrs median NIHSS was 7 (IQR 6-9). There was no neurological improvement (ΔNIHSS) in patients with greater than 6 areas of involvement (p&lt;0.001).Glucose was significantly higher in patients without ΔNIHSS compared to patients with ΔNIHSS (p=0.01). The most eloquent regions as measured by absence of delta NIHSS&gt;10 despite recanalization were basal ganglia (OR 0.03 95%CI 0.004-0.25, p=0.001),posterior limb of internal capsule (OR 0.10 95%CI 0.01-0.85, p&lt;0.001) ,M2 ( OR 0.06 95%CI 0.01-0.25, p&lt;0.001)and C2 (core of corona radiata)(OR 0.12 95%CI 0.04-0.35 p&lt;0.001). Conclusions ΔNIHSS at 24 hours after recanalization is high in a situation when more anatomical regions are involved. Patients with more than six infarcted regions had no improvement in ΔNIHSS. Patients with baseline involvement (ischemic core) of the corona radiata (C2), M2 (temporal lobe), basal ganglia and internal capsule have the least chance for significant ΔNIHSS improvement.