Alexandre Y. Poppe

Admission Hyperglycemia Predicts a Worse Outcome in Stroke Patients Treated With Intravenous Thrombolysis

OBJECTIVE Admission hyperglycemia has been associated with worse outcomes in ischemic stroke. We hypothesized that hyperglycemia (glucose >8.0 mmol/l) in the hyperacute phase would be independently associated with increased mortality, symptomatic intracerebral hemorrhage (SICH), and poor functional status at 90 days in stroke patients treated with intravenous tissue plasminogen activator (IV-tPA). RESEARCH DESIGN AND METHODS Using data from the prospective, multicenter Canadian Alteplase for Stroke Effectiveness Study (CASES), the association between admission glucose >8.0 mmol/l and mortality, SICH, and poor functional status at 90 days (modified Rankin Scale >1) was examined. Similar analyses examining glucose as a continuous measure were conducted. RESULTS Of 1,098 patients, 296 (27%) had admission hyperglycemia, including 18% of those without diabetes and 70% of those with diabetes. After multivariable logistic regression, admission hyperglycemia was found to be independently associated with increased risk of death (adjusted risk ratio 1.5 [95% CI 1.2–1.9]), SICH (1.69 [0.95–3.00]), and a decreased probability of a favorable outcome at 90 days (0.7 [0.5–0.9]). An incremental risk of death and SICH and unfavorable 90-day outcomes was observed with increasing admission glucose. This observation held true for patients with and without diabetes. CONCLUSIONS In this cohort of IV-tPA–treated stroke patients, admission hyperglycemia was independently associated with increased risk of death, SICH, and poor functional status at 90 days. Treatment trials continue to be urgently needed to determine whether this is a modifiable risk factor for poor outcome.

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.

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.

Normal Magnetic Resonance Perfusion-Weighted Imaging in Lacunar Infarcts Predicts a Low Risk of Early Deterioration

Background: Current clinical tools to identify lacunar infarct patients at risk of deterioration are inadequate, and imaging techniques to predict fluctuation and deterioration would be of value. We sought to determine the occurrence of MRI perfusion-weighted imaging (PWI) abnormalities in lacunes, and whether they help predict clinical and radiological outcome. Methods: Patients with lacunar stroke or TIA were selected from a prospective MR imaging study. MRI was performed within 24 h of the event and follow-up imaging completed at 30 or 90 days. Baseline perfusion maps were qualitatively assessed and infarct volumes measured. Early clinical deterioration (NIHSS worsening of ≥3 points within 72 h of event) and 90-day modified Rankin Scale score (mRS) were recorded. Results: Twenty-two patients were included. Fifteen (68.2%) had abnormal PWI at the site of the diffusion-weighted imaging lesion. Patients with abnormal PWI were more likely to have stroke than TIA as their index event (RR 2.2, 95% CI 0.9–5.2, p = 0.02). Early clinical deterioration occurred in 4 patients (18.2%), all of whom had abnormal PWI. PWI lesions were not associated with a higher 90-day NIHSS or mRS score, nor did they predict infarct volume growth. Conclusions: MR-PWI abnormalities are seen in two thirds of lacunar infarcts, and are associated with stroke rather than TIA. Normal PWI identifies patients at low risk of early clinical deterioration.

Intra-Arterial Therapy and Post-Treatment Infarct Volumes Insights From the ESCAPE Randomized Controlled Trial

Background and Purpose— The goal of reperfusion therapy in acute ischemic stroke is to limit brain infarction. The objective of this study was to investigate whether the beneficial effect of endovascular treatment on functional outcome could be explained by a reduction in post-treatment infarct volume. Methods— The Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial was a multicenter randomized open-label trial with blinded outcome evaluation. Among 315 enrolled subjects (endovascular treatment n=165; control n=150), 314 subject’s infarct volumes at 24 to 48 hours on magnetic resonance imaging (n=254) or computed tomography (n=60) were measured. Post-treatment infarct volumes were compared by treatment assignment and recanalization/reperfusion status. Appropriate statistical models were used to assess relationship between baseline clinical and imaging variables, post-treatment infarct volume, and functional status at 90 days (modified Rankin Scale). Results— Median post-treatment infarct volume in all subjects was 21 mL (interquartile range =65 mL), in the intervention arm, 15.5 mL (interquartile range =41.5 mL), and in the control arm, 33.5 mL (interquartile range =84 mL; P<0.01). Baseline National Institute of Health Stroke Scale (P<0.01), site of occlusion (P<0.01), baseline noncontrast computed tomographic scan Alberta Stroke Program Early CT score (ASPECTS) (P<0.01), and recanalization (P<0.01) were independently associated with post-treatment infarct volume, whereas age, sex, treatment type, intravenous alteplase, and time from onset to randomization were not (P>0.05). Post-treatment infarct volume (P<0.01) and delta National Institute of Health Stroke Scale (P<0.01) were independently associated with 90-day modified Rankin Scale, whereas laterality (left versus right) was not. Conclusions— These results support the primary results of the ESCAPE trial and show that the biological underpinning of the success of endovascular therapy is a reduction in infarct volume. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335.

Silent ischemic lesions in young adults with first stroke are associated with recurrent stroke

Objective: To determine the association between silent ischemic lesions (SILs) on baseline brain MRI and recurrent stroke in young adults with first-ever ischemic stroke. Methods: This was a single-center retrospective study of adult patients aged 18–50 years with first-ever ischemic stroke investigated by brain MRI between 2002 and 2009. Silent brain infarcts (SBIs) were defined as focal T2 hyperintensities ≥3 mm without corresponding focal symptoms, and leukoaraiosis was defined as focal, multifocal, or confluent hyperintensities on T2-weighted sequences. The primary outcome was recurrent stroke. A forward stepwise Cox regression model was used to determine whether SILs were independently associated with recurrent stroke. Results: A total of 271 eligible patients were identified in the database: 89 did not undergo MRI imaging and 12 patients had inadequate follow-up, leaving a study population of 170 patients. MRI demonstrated SILs in 48 of 170 (28.2) patients. No patients had isolated leukoaraiosis. Hypertension (p = 0.049), migraine with aura (p = 0.02), and cardiovascular disease (p = 0.04) were associated with SIL. Mean follow-up duration was 25 ± 7 months. Among patients with SILs, 11 of 48 (23%) had a recurrent stroke vs 8 of 122 (6.5%) patients without SIL (p = 0.003). After multivariate Cox regression, SILs remained independently associated with recurrent stroke (hazard ratio [HR] 3.2, 95% confidence interval [CI] 1.2−8.6, p = 0.02), as did the combination of SBIs and leukoaraiosis (HR 7.3, 95% CI 2.3−22.9, p = 0.003). Conclusions: In adults ≤50 years old with first-ever ischemic stroke, SILs are common and independently predict recurrent stroke.

Good is not Good Enough: The Benchmark Stroke Door-to-Needle Time Should be 30 Minutes.

Noreen Kamal, Oscar Benavente, Karl Boyle, Brian Buck, Ken Butcher, Leanne K. Casaubon,RobertCote,AndrewMDemchuk,YanDeschaintre,DarDowlatshahi,GordonJGubitz,GaryHunter,Tom Jeerakathil, Albert Jin, Eddy Lang, Sylvain Lanthier, Patrice Lindsay, Nancy Newcommon,Jennifer Mandzia, Colleen M. Norris, Wes Oczkowski, Celine Odier, Stephen Phillips,Alexandre Y Poppe, Gustavo Saposnik, Daniel Selchen, Ashfaq Shuaib, Frank Silver, Eric E Smith,Grant Stotts, Michael Suddes, Richard H. Swartz, Philip Teal, Tim Watson, Michael D. Hill

Should you thrombolyse all or any stroke patients with baseline National Institutes of Health stroke scale scores < or = 5?

er [65 8 12 vs. 70 8 13 years (mean 8 SD); p ! 0.01], and more commonly had coronary artery disease (34.7 vs. 24.2%; p = 0.5) and hypercholesterolemia (29.3 vs. 18.6%; p = 0.03). Other baseline characteristics are provided in table 1 . In the minor stroke cohort, time from symptom onset to tPA bolus was a mean of 14 min longer (163 vs. 149 min; p ! 0.01). Symptomatic intracerebral hemorrhage was identified in 2.6% (vs. 4.7%; p = 0.572). Favorable outcome (mRS score = 0–1) at 90 days was more frequent (74.7 vs. 34.7%; RR = 2.2, 95% CI = 1.8–2.5, p ! 0.001) and mortality was lower (8 vs. 22.9%; RR = 0.35, 95% CI = 0.16–0.76, p = 0.002). Favorable outcomes were not different (81.3 vs. 74.7%, mRS score = 0–1, p = 0.75) compared to a placebo-treated group with baseline NIHSS scores ̂ 5 (n = 16) from the NINDS tPA trial [4] .

Early CT changes in patients admitted for thrombectomy Intrarater and interrater agreement

Objective: To systematically review the literature and assess agreement on the Alberta Stroke Program Early CT Score (ASPECTS) among clinicians involved in the management of thrombectomy candidates. Methods: Studies assessing agreement using ASPECTS published from 2000 to 2015 were reviewed. Fifteen raters reviewed and scored the anonymized CT scans of 30 patients recruited in a local thrombectomy trial during 2 independent sessions, in order to study intrarater and interrater agreement. Agreement was measured using intraclass correlation coefficients (ICCs) and Fleiss kappa statistics for ASPECTS and dichotomized ASPECTS at various cutoff values. Results: The review yielded 30 articles reporting 40 measures of agreement. Populations, methods, analyses, and results were heterogeneous (slight to excellent agreement), precluding a meta-analysis. When analyzed as a categorical variable, intrarater agreement was slight to moderate (κ = 0.042–0.469); it reached a substantial level (κ > 0.6) in 11/15 raters when the score was dichotomized (0–5 vs 6–10). The interrater ICCs varied between 0.672 and 0.811, but agreement was slight to moderate (κ = 0.129–0.315). Even in the best of cases, when ASPECTS was dichotomized as 0–5 vs 6–10, interrater agreement did not reach a substantial level (κ = 0.561), which translates into at least 5 of 15 raters not giving the same dichotomized verdict in 15% of patients. Conclusions: In patients considered for thrombectomy, there may be insufficient agreement between clinicians for ASPECTS to be reliably used as a criterion for treatment decisions.

Early Trajectory of Stroke Severity Predicts Long-Term Functional Outcomes in Ischemic Stroke Subjects: Results From the ESCAPE Trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times).

Background and Purpose— The trajectory of neurological improvement after stroke treatment is clinically likely to be an important prognostic signal. We compared the accuracy of early longitudinal National Institutes of Health Stroke Scale (NIHSS) measurement versus other early markers of stroke severity post treatment in predicting subjects’ 90-day stroke outcome. Methods— Data are from the Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times). Stroke severity was assessed at baseline, 1, 2, 5, 30, and 90 days. Subjects’ functional outcome was assessed using the modified Rankin Scale at baseline, 30 days, and 90 days. Group-based trajectory model was used to identify distinct subgroups of longitudinal trajectories of NIHSS measured over the first 2, 5, and 30 days. The accuracy of baseline NIHSS, infarct volume, 24-hour change in NIHSS, infarct volume, and disease severity trajectory subgroups in predicting 90-day stroke outcome were assessed using logistic regression analysis. Results— Group-based trajectory model of the 2-day longitudinal NIHSS data revealed 3 distinct subgroups of NIHSS trajectories—large improvement (41.6%), minimal improvement (31.1%), and no improvement (27.3%) subgroups. Individuals in the large improvement group were more likely were more likely to exhibit good outcomes after 90 days than those in the minimal improvement or no improvement subgroup. Among candidate predictors, the 2-day trajectory subgroup variable was the most accurate in predicting 90-day modified Rankin Scale at 84.5%. Conclusions— Early trajectory of neurological improvement defined by 2-day longitudinal NIHSS data predicts functional outcomes with greater accuracy than other common variables. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335.