Muneer Eesa

Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke

BACKGROUND Among patients with a proximal vessel occlusion in the anterior circulation, 60 to 80% of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment. We evaluated rapid endovascular treatment in addition to standard care in patients with acute ischemic stroke with a small infarct core, a proximal intracranial arterial occlusion, and moderate-to-good collateral circulation. METHODS We randomly assigned participants to receive standard care (control group) or standard care plus endovascular treatment with the use of available thrombectomy devices (intervention group). Patients with a proximal intracranial occlusion in the anterior circulation were included up to 12 hours after symptom onset. Patients with a large infarct core or poor collateral circulation on computed tomography (CT) and CT angiography were excluded. Workflow times were measured against predetermined targets. The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention would lead to lower scores on the modified Rankin scale than would control care (shift analysis). RESULTS The trial was stopped early because of efficacy. At 22 centers worldwide, 316 participants were enrolled, of whom 238 received intravenous alteplase (120 in the intervention group and 118 in the control group). In the intervention group, the median time from study CT of the head to first reperfusion was 84 minutes. The rate of functional independence (90-day modified Rankin score of 0 to 2) was increased with the intervention (53.0%, vs. 29.3% in the control group; P<0.001). The primary outcome favored the intervention (common odds ratio, 2.6; 95% confidence interval, 1.7 to 3.8; P<0.001), and the intervention was associated with reduced mortality (10.4%, vs. 19.0% in the control group; P=0.04). Symptomatic intracerebral hemorrhage occurred in 3.6% of participants in intervention group and 2.7% of participants in control group (P=0.75). CONCLUSIONS Among patients with acute ischemic stroke with a proximal vessel occlusion, a small infarct core, and moderate-to-good collateral circulation, rapid endovascular treatment improved functional outcomes and reduced mortality. (Funded by Covidien and others; ESCAPE ClinicalTrials.gov number, NCT01778335.).

Analysis of Workflow and Time to Treatment on Thrombectomy Outcome in the Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) Randomized, Controlled Trial

Background— The Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial used innovative imaging and aggressive target time metrics to demonstrate the benefit of endovascular treatment in patients with acute ischemic stroke. We analyze the impact of time on clinical outcome and the effect of patient, hospital, and health system characteristics on workflow within the trial. Methods and Results— Relationship between outcome (modified Rankin Scale) and interval times was modeled by using logistic regression. Association between time intervals (stroke onset to arrival in endovascular-capable hospital, to qualifying computed tomography, to groin puncture, and to reperfusion) and patient, hospital, and health system characteristics were modeled by using negative binomial regression. Every 30-minute increase in computed tomography-to-reperfusion time reduced the probability of achieving a functionally independent outcome (90-day modified Rankin Scale 0–2) by 8.3% (P=0.006). Symptom onset-to-imaging time was not associated with outcome (P>0.05). Onset-to-endovascular hospital arrival time was 42% (34 minutes) longer among patients receiving intravenous alteplase at the referring hospital (drip and ship) versus direct transfer (mothership). Computed tomography-to-groin puncture time was 15% (8 minutes) shorter among patients presenting during work hours versus off hours, 41% (24 minutes) shorter in drip-ship patients versus mothership, and 43% (22 minutes) longer when general anesthesia was administered. The use of a balloon guide catheter during endovascular procedures shortened puncture-to-reperfusion time by 21% (8 minutes). Conclusions— Imaging-to-reperfusion time is a significant predictor of outcome in the ESCAPE trial. Inefficiencies in triaging, off-hour presentation, intravenous alteplase administration, use of general anesthesia, and endovascular techniques offer major opportunities for improvement in workflow. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335.

CTA Collateral Status and Response to Recanalization in Patients with Acute Ischemic Stroke

BACKGROUND AND PURPOSE: Collateral status at baseline is an independent determinant of clinical outcome among patients with acute ischemic stroke. We sought to identify whether the association between recanalization after intra-arterial acute stroke therapy and favorable clinical response is modified by the presence of good collateral flow assessed on baseline CTA. MATERIALS AND METHODS: Data are from the Keimyung Stroke Registry, a prospective cohort study of patients with acute ischemic stroke from Daegu, South Korea. Patients with M1 segment MCA with or without intracranial ICA occlusions on baseline CTA from May 2004 to July 2009 who also had baseline MR imaging were included. Two readers blinded to all clinical information assessed baseline and follow-up imaging. Leptomeningeal collaterals on baseline CTA were assessed by consensus by use of the regional leptomeningeal score. RESULTS: Among 84 patients (mean age, 65.2 ± 13.2 years; median NIHSS score, 14; interquartile range, 8.5), median time from stroke onset to initial MR imaging was 164 minutes. TICI 2b–3 recanalization was achieved in 38.1% of patients and mRS 0–2 at 90 days in 35.8% of patients. In a multivariable model, the interaction between collateral status and recanalization was significant. Only patients with intermediate or good collaterals who recanalized showed a statistically significant association with good clinical outcome (rate ratio = 3.8; 95% CI, 1.2–12.1). Patients with good and intermediate collaterals who did not achieve recanalization and patients with poor collaterals, even if they achieved recanalization, did not do well. CONCLUSIONS: Patients with good or intermediate collaterals on CTA benefit from intra-arterial therapy, whereas patients with poor collaterals do not benefit from treatment.

Evaluation of Interval Times From Onset to Reperfusion in Patients Undergoing Endovascular Therapy in the Interventional Management of Stroke III Trial

Background— Meaningful delays occurred in the Interventional Management of Stroke (IMS) III trial. Analysis of the work flow will identify factors contributing to the in-hospital delays. Methods and Results— In the endovascular arm of the IMS III trial, the following time intervals were calculated: stroke onset to emergency department arrival; emergency department to computed tomography (CT); CT to intravenous tissue plasminogen activator start; intravenous tissue plasminogen activator start to randomization; randomization to groin puncture; groin puncture to thrombus identification; thrombus identification to start of endovascular therapy; and start of endovascular therapy to reperfusion. The effects of enrollment time, CT angiography use, interhospital transfers, and intubation on work flow were evaluated. Delays occurred notably in the time intervals from intravenous tissue plasminogen activator initiation to groin puncture (median 84 minutes) and start of endovascular therapy to reperfusion (median 85 minutes). The CT to groin puncture time was significantly shorter during working hours than after. Times from emergency department to reperfusion and groin puncture to reperfusion decreased over the trial period. Patients with CT angiography had shorter emergency department to reperfusion and onset to reperfusion times. Transfer of patients resulted in a longer onset to reperfusion time compared with those treated in the same center. Age, sex, National Institutes of Health Stroke Scale score, and intubation did not affect delays. Conclusions— Important delays were identified before reperfusion in the IMS III trial. Delays decreased as the trial progressed. Use of CT angiography and endovascular treatment in the same center were associated with time savings. These data may help in optimizing work flow in current and future endovascular trials. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424.

Acute Corticospinal Tract Wallerian Degeneration Is Associated With Stroke Outcome

Background and Purpose— In children with stroke, poor motor outcome is associated with early Wallerian degeneration of the corticospinal tract that is seen on diffusion-weighted MRI. In this study we test the hypothesis that early diffusion changes also occur in the corticospinal tract (CST) of adults after stroke and that these lesions are associated with poor outcome. Methods— In this retrospective study, we assessed images from a serial MRI study of adults with acute middle cerebral/internal carotid artery stroke. MRI-negative TIA patients served as controls. Custom software measured signal along the CST on different sequences, including the apparent diffusion coefficient (ADC). Visual detection of abnormal signal by blinded neuroradiologists was also evaluated. We then determined associations between CST signal changes and 3-month motor outcome (NIHSS score). Results— Thirty-eight patients (20 stroke/18 control) were included. ADC measures were much more accurate than other MRI sequences for detection of degeneration in the CST. The ADC decreased in a time-dependent fashion in the CST of patients with poor motor outcome but not in those with good outcome. Changes in ADC were maximal at 7 days. Neuroradiologists could visually detect these changes with accuracy comparable to the software method. Conclusion— CST ADC decreases after acute stroke in patients with poor motor outcome and may represent early Wallerian degeneration. Recognition of this imaging marker may improve early outcome prediction and patient selection for rehabilitation and neuroprotection trials.

Toxic and Acquired Metabolic Encephalopathies: MRI Appearance

OBJECTIVE The differential diagnosis of patients presenting with acute encephalopathy is broad. Imaging can help in narrowing the differential in many cases. We pictorially review the more classic MRI features of several acute toxic and acquired metabolic encephalopathies. CONCLUSION After completing this article, the reader will have knowledge of the more common imaging appearances of toxic and acquired metabolic encephalopathies, which will help in correctly identifying the cause of encephalopathy in some patients.

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.

Early Reperfusion Rates with IV tPA Are Determined by CTA Clot Characteristics

These authors evaluated CTA studies of 228 patients paying special attention to the clot features, and correlated these features with early reperfusion rates. Clot features that predicted successful early reperfusion included: shorter clot, residual flow within the clot, and distal location. Reperfusion was achieved in only 8% of patients with longer and proximal clots and in those without residual flow. BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Our study shows that clot characteristics on CTA help physicians estimate a range of early reperfusion rates with IV tPA.

Quantomo: validation of a computer-assisted methodology for the volumetric analysis of intracerebral haemorrhage.

Background Volume measurements of intracerebral haemorrhage are prognostically important and are increasingly used in clinical trials to measure the effects of potential interventions. The purpose of this work is to establish the reliability of haematoma volume measurements obtained using a computer-assisted method called Quantomo (for quantitative tomography) and the ABC/2 method. Hypothesis Quantomo reliably detects smaller changes in intracerebral haemorrhage volume as compared with the ABC/2 method because computer-assisted volume measurements are tailored to measure the geometry of individual haematoma volumes whereas the ABC/2 method approximates all haematoma volumes as ellipsoids. Methods Thirty randomly selected computed tomography scans with intracerebral haemorrhage were measured by four raters a total of four times each (two sessions using Quantomo and two using the ABC/2 method). Interrater and intrarater reliability for both techniques were calculated simultaneously using a two-way random-effects analysis of variance model. The precision of intracerebral haemorrhage volume measurement was quantified as the minimum detectable difference with 95% confidence intervals. Results The median (first quartile and third quartile) intracerebral haemorrhage volume measurements of all rater and sessions for Quantomo were 32·7 ml (6·2 and 54·4 ml) and for ABC/2 40·7 ml (8·6 and 76·0 ml). Quantomo intracerebral haemorrhage volume measurements were more precise, having an inter- and intrarater minimum detectable difference of 8·1 and 5·3 ml, while the inter- and intrarater minimum detectable difference for ABC/2 were 37·0 and 15·7 ml. Conclusions Quantomo is a computer-assisted methodology that is more reliable for quantifying intracerebral haemorrhage volume as compared with the ABC/2 method.

Not All “Successful” Angiographic Reperfusion Patients Are an Equal Validation of a Modified TICI Scoring System

Rapid reperfusion of the entire territory distal to vascular occlusions is the aim of stroke interventions. Recent studies defined successful reperfusion as establishing some perfusion with distal branch filling of <50% of territory visualized (Thrombolysis In Cerebral Infarction “TICI” 2a) or more. We investigate the importance of the quality of final reperfusion and whether a revision of the successful reperfusion definition is warranted. We retrospectively evaluated a prospective database of anterior circulation strokes treated using stentrievers to assess the quality of final reperfusion using two scores: the traditional TICI score and a modified TICI score. The modified TICI score includes an additional category (TICI 2c): near complete perfusion except for slow flow or distal emboli in a few distal cortical vessels. We compared different cut-off definitions of reperfusion (TICI 2a–3 vs. TICI-2b–3 vs. TICI 2c–3) using the area under the curve to identify their correlation with a favorable 90-day outcome (mRS≤2). In our cohort of 110 patients, 90% achieved TICI 2a-3 reperfusion with 80% achieving TICI 2b-3 and 55.5% achieving TICI 2c-3. The proportion of patients with a favorable 90-day outcome was higher in the TICI 2c (62.5%) compared to TICI 2b (44.4%) or TICI 2a (45.5%) but similar to the TICI 3 group (75.9%). A TICI 2c-3 reperfusion had a better predictive value than TICI 2b-3 for 90-day mRS 0–1. Defining successful reperfusion as TICI 2c/3 has merits. In this cohort, there was evidence toward faster recovery and better outcomes in patients with the TICI 2c vs. the traditional TICI 2b grade.