Mohammed A. Almekhlafi

Multiphase CT Angiography: A New Tool for the Imaging Triage of Patients with Acute Ischemic Stroke

PURPOSE To describe the use of an imaging selection tool, multiphase computed tomographic (CT) angiography, in patients with acute ischemic stroke (AIS) and to demonstrate its interrater reliability and ability to help determine clinical outcome. MATERIALS AND METHODS The local ethics board approved this study. Data are from the pilot phase of PRoveIT, a prospective observational study analyzing utility of multimodal imaging in the triage of patients with AIS. Patients underwent baseline unenhanced CT, single-phase CT angiography of the head and neck, multiphase CT angiography, and perfusion CT. Multiphase CT angiography generates time-resolved images of pial arteries. Pial arterial filling was scored on a six-point ordinal scale, and interrater reliability was tested. Clinical outcomes included a 50% or greater decrease in National Institutes of Health Stroke Scale (NIHSS) over 24 hours and 90-day modified Rankin Scale (mRS) score of 0-2. The ability to predict clinical outcomes was compared between single-phase CT angiography, multiphase CT angiography, and perfusion CT by using receiver operating curve analysis, Akaike information criterion (AIC), and Bayesian information criterion (BIC). RESULTS A total of 147 patients were included. Interrater reliability for multiphase CT angiography is excellent (n = 30, κ = 0.81, P < .001). At receiver operating characteristic curve analysis, the ability to predict clinical outcome is modest (C statistic = 0.56, 95% confidence interval [CI]: 0.52, 0.63 for ≥50% decrease in NIHSS over 24 hours; C statistic = 0.6, 95% CI: 0.53, 0.68 for 90-day mRS score of 0-2) but better than that of models using single-phase CT angiography and perfusion CT (P < .05 overall). With AIC and BIC, models that use multiphase CT angiography are better than models that use single-phase CT angiography and perfusion CT for a decrease of 50% or more in NIHSS over 24 hours (AIC = 166, BIC = 171.7; values were lowest for multiphase CT angiography) and a 90-day mRS score of 0-2 (AIC = 132.1, BIC = 137.4; values were lowest for multiphase CT angiography). CONCLUSION Multiphase CT angiography is a reliable tool for imaging selection in patients with AIS.

Recurrent cerebral ischemia in medically treated patent foramen ovale: A meta-analysis

Background: Among patients with a patent foramen ovale (PFO) and a prior cryptogenic ischemic stroke or TIA, the absolute and relative risk of recurrent events is unclear. Methods: We conducted a systematic review and meta-analysis of clinical studies in any language published up to February 2008. We included studies reporting original data on recurrent cerebrovascular events in patients with prior cryptogenic stroke or TIA and PFO. Two authors independently extracted data and evaluated study quality. Results: We identified 15 eligible studies, four with a non-PFO comparison group. In these four studies, the pooled relative risk (RR) for recurrent ischemic stroke or TIA in patients with vs without a PFO was 1.1 (95% confidence interval [CI] 0.8 to 1.5). For ischemic stroke, the pooled RR was 0.8 (95% CI 0.5 to 1.3). We tabulated the absolute rate of recurrent events in all 15 studies. The pooled absolute rate of recurrent ischemic stroke or TIA in patients with PFO was 4.0 events per 100 person-years (95% CI 3.0 to 5.1) while the rate of recurrent ischemic stroke was 1.6 events per 100 person-years (95% CI 1.1 to 2.1). Conclusions: In medically treated patients with prior cryptogenic stroke, while the absolute rate of recurrent events is variable, available evidence does not support an increased relative risk of recurrent ischemic events in those with vs without a patent foramen ovale. Patent foramen ovale closure in these patients cannot be recommended until the results of ongoing clinical trials are reported.

Optimal Workflow and Process-Based Performance Measures for Endovascular Therapy in Acute Ischemic Stroke Analysis of the Solitaire FR Thrombectomy for Acute Revascularization Study

Background and Purpose— We report on workflow and process-based performance measures and their effect on clinical outcome in Solitaire FR Thrombectomy for Acute Revascularization (STAR), a multicenter, prospective, single-arm study of Solitaire FR thrombectomy in large vessel anterior circulation stroke patients. Methods— Two hundred two patients were enrolled across 14 centers in Europe, Canada, and Australia. The following time intervals were measured: stroke onset to hospital arrival, hospital arrival to baseline imaging, baseline imaging to groin puncture, groin puncture to first stent deployment, and first stent deployment to reperfusion. Effects of time of day, general anesthesia use, and multimodal imaging on workflow were evaluated. Patient characteristics and workflow processes associated with prolonged interval times and good clinical outcome (90-day modified Rankin score, 0–2) were analyzed. Results— Median times were onset of stroke to hospital arrival, 123 minutes (interquartile range, 163 minutes); hospital arrival to thrombolysis in cerebral infarction (TICI) 2b/3 or final digital subtraction angiography, 133 minutes (interquartile range, 99 minutes); and baseline imaging to groin puncture, 86 minutes (interquartile range, 24 minutes). Time from baseline imaging to puncture was prolonged in patients receiving intravenous tissue-type plasminogen activator (32-minute mean delay) and when magnetic resonance–based imaging at baseline was used (18-minute mean delay). Extracranial carotid disease delayed puncture to first stent deployment time on average by 25 minutes. For each 1-hour increase in stroke onset to final digital subtraction angiography (or TICI 2b/3) time, odds of good clinical outcome decreased by 38%. Conclusions— Interval times in the STAR study reflect current intra-arterial therapy for patients with acute ischemic stroke. Improving workflow metrics can further improve clinical outcome. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01327989.

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.

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.

A Meta-Analysis of Observational Intra-Arterial Stroke Therapy Studies Using the Merci Device, Penumbra System, and Retrievable Stents

BACKGROUND AND PURPOSE: The time from arterial puncture to successful recanalization is an important milestone toward timely recanalization. With the significant improvement in recanalization rates by using thrombectomy devices, procedural time to recanalization is becoming a determinant factor in choosing among available devices. We aimed to assess the impact of time to recanalization on the outcome of intra-arterial stroke therapies. MATERIALS AND METHODS: We conducted a meta-analysis of studies reporting procedural times in patients with stroke treated with the MD, PS, and RS. RESULTS: We identified 16 eligible studies: 4 on the MD (n = 357), 8 on the PS (n = 455), and 4 on RS (n = 113). Merci device studies described total procedural duration, while PS and RS studies described puncture-to-recanalization times. With a random-effects model, mean procedural duration for the MD was 120 minutes (95% CI, 105.7–134.2 minutes). Mean puncture to recanalization time for the PS was 64.6 minutes (95% CI, 44.4–84.8 minutes) and 54.7 minutes for RS (95% CI, 47.3–62.2 minutes). Successful recanalization was achieved in 211 of 357 patients (59.1%) in the MD studies (95% CI, 49.3–77.7), 394 of 455 (86.6%) in the PS studies (95% CI, 84.1–93.8), and 105 of 113 (92.9%) in the RS studies (95% CI, 90.9–99.9). Functional independence (mRS ≤2) was achieved in 31.5% of patients in the MD studies, 36.6% in the PS studies, and 46.9% in the RS studies. CONCLUSIONS: The use of the PS and RS was associated with comparable procedural time to recanalization. Available data did not allow this parameter to be determined for trials using the MD. Retrievable stents achieved the highest rate of successful recanalization and functional outcome and the lowest mortality.

Calcification and endothelialization of thrombi in acute stroke

We report chronic histopathological features in thrombi mechanically retrieved from five acute ischemic stroke patients with a median age of 68 years and a median pretreatment National Institutes of Health Stroke Scale score of 13. Early endothelialization occurred over and within the thrombus, and calcifications were seen, in addition to the usual acute laminar fibrin, intervening red blood cells, and neutrophils. The effectiveness of tissue plasminogen activator in clot dissolution might be affected by these features, if extensive. Thrombus composition could critically determine the success of chemical thrombolysis. Our results should stimulate the development of imaging modalities to determine thrombus composition. Ann Neurol 2008

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.