Jenny P. Tsai

Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging

Background Thrombectomy is currently recommended for eligible patients with stroke who are treated within 6 hours after the onset of symptoms. Methods We conducted a multicenter, randomized, open‐label trial, with blinded outcome assessment, of thrombectomy in patients 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was not yet infarcted. Patients with proximal middle‐cerebral‐artery or internal‐carotid‐artery occlusion, an initial infarct size of less than 70 ml, and a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more were randomly assigned to endovascular therapy (thrombectomy) plus standard medical therapy (endovascular‐therapy group) or standard medical therapy alone (medical‐therapy group). The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at day 90. Results The trial was conducted at 38 U.S. centers and terminated early for efficacy after 182 patients had undergone randomization (92 to the endovascular‐therapy group and 90 to the medical‐therapy group). Endovascular therapy plus medical therapy, as compared with medical therapy alone, was associated with a favorable shift in the distribution of functional outcomes on the modified Rankin scale at 90 days (odds ratio, 2.77; P<0.001) and a higher percentage of patients who were functionally independent, defined as a score on the modified Rankin scale of 0 to 2 (45% vs. 17%, P<0.001). The 90‐day mortality rate was 14% in the endovascular‐therapy group and 26% in the medical‐therapy group (P=0.05), and there was no significant between‐group difference in the frequency of symptomatic intracranial hemorrhage (7% and 4%, respectively; P=0.75) or of serious adverse events (43% and 53%, respectively; P=0.18). Conclusions Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle‐cerebral‐artery or internal‐carotid‐artery occlusion and a region of tissue that was ischemic but not yet infarcted. (Funded by the National Institute of Neurological Disorders and Stroke; DEFUSE 3 ClinicalTrials.gov number, NCT02586415.)

A multicenter randomized controlled trial of endovascular therapy following imaging evaluation for ischemic stroke (DEFUSE 3)

Rationale Early reperfusion in patients experiencing acute ischemic stroke is effective in patients with large vessel occlusion. No randomized data are available regarding the safety and efficacy of endovascular therapy beyond 6 h from symptom onset. Aim The aim of the study is to demonstrate that, among patients with large vessel anterior circulation occlusion who have a favorable imaging profile on computed tomography perfusion or magnetic resonance imaging, endovascular therapy with a Food and Drug Administration 510 K-cleared mechanical thrombectomy device reduces the degree of disability three months post stroke. Design The study is a prospective, randomized, multicenter, phase III, adaptive, blinded endpoint, controlled trial. A maximum of 476 patients will be randomized and treated between 6 and 16 h of symptom onset. Procedures Patients undergo imaging with computed tomography perfusion or magnetic resonance diffusion/perfusion, and automated software (RAPID) determines if the Target Mismatch Profile is present. Patients who meet both clinical and imaging selection criteria are randomized 1:1 to endovascular therapy plus medical management or medical management alone. The individual endovascular therapist chooses the specific device (or devices) employed. Study outcomes The primary endpoint is the distribution of scores on the modified Rankin Scale at day 90. The secondary endpoint is the proportion of patients with modified Rankin Scale 0–2 at day 90 (indicating functional independence). Analysis Statistical analysis for the primary endpoint will be conducted using a normal approximation of the Wilcoxon–Mann–Whitney test (the generalized likelihood ratio test).

Computed tomographic perfusion to Predict Response to Recanalization in ischemic stroke.

To assess the utility of computed tomographic (CT) perfusion for selection of patients for endovascular therapy up to 18 hours after symptom onset.

A Prescription at Discharge Improves Long-term Adherence for Secondary Stroke Prevention

BACKGROUND Medication adherence is important for optimal secondary stroke prevention. We evaluated short-term adherence to antihypertensive and lipid-lowering agents after a new ischemic stroke, as predictor of adherence at 1 and 2 years. METHODS A 5-year cohort of patients from 11 institutions in the Registry of the Canadian Stroke Network was linked to population-based administrative health records. Patients diagnosed with acute ischemic stroke and discharged home were included. Medication adherence was assessed through documented prescription filling at 7 days, 1 year, and 2 years. RESULTS From 2003 to 2008, 6437 ischemic stroke patients were discharged home from hospital, and 1126 patients filled a prescription for antihypertensive and lipid-lowering agents within 7 days of discharge. Patients provided with a prescription at discharge were more likely to show adherence at 7 days. Adherence at 1 year remains higher in these patients for antihypertensive (93.8% vs. 87.7%; odds ratio [OR], 2.31; 95% confidence interval [CI], 1.69-3.16), lipid-lowering agents (88% vs. 81.6%; OR, 1.77; 95% CI, 1.36-2.32), or both (85.8% vs. 79.9%; OR, 1.72; 95% CI, 1.32-2.25). Findings are similar at 2 years for antihypertensive (92.2% vs. 87.7%; OR, 1.78; 95% CI, 1.3-2.43), lipid-lowering agents (82.6% vs. 79.0%; OR, 1.31; 95% CI, 1.01-1.69), or both (81.1% vs. 77.0%; OR, 1.4; 95% CI, 1.09-1.82). CONCLUSIONS Provision of a prescription strengthens adherence at 1 week from discharge for both prior and new users of antihypertensive and lipid-lowering drugs. Medication adherence at 1 week after discharge for acute ischemic stroke predicts adherence for secondary preventive therapies at 1 and 2 years.

CT Perfusion to Predict Response to Recanalization in Ischemic Stroke

To assess the utility of computed tomographic (CT) perfusion for selection of patients for endovascular therapy up to 18 hours after symptom onset.

Influenza-Associated Neurological Complications

While mostly diagnosed in the pediatric population, neurological complications of pandemic influenza A infection may affect young and previously healthy adults, and may follow a fulminant, severe, and occasionally fatal course. We reviewed severe neurological complications secondary to influenza infection reported in the literature, in attempt to outline recurrent syndromes that may assist the clinician in making a timely diagnosis. Vigilance and awareness of these clinical entities are key in the neurologist and intensivist’s role in surveillance and early recognition of pandemic influenza, and in ensuring improved survival for affected patients.

Reperfusion versus recanalization: the winner is….

See related article, p 1582. The terms reperfusion and recanalization are sometimes erroneously used interchangeably when referring to outcomes of thrombolytic or endovascular therapies. Recanalization and reperfusion are neither discrete nor static measures and although achieving one often implies the other has also occurred. Arterial obstructions and perfusion deficits can both evolve independently over time, in the early hours not only after stroke onset but also after therapeutic interventions. Distinguishing reperfusion from recanalization can be challenging in the clinical arena because currently available noninvasive measurements from multimodal computed tomography or magnetic resonance imaging (MRI) have imperfect sensitivity and specificity. In this issue of Stroke , Cho et al1 address the question of whether reperfusion or recanalization is a better predictor of a variety of outcomes in patients with acute stroke. The authors observed that successful recanalization consistently led to reperfusion of the ischemic territory; however, recanalization was not a prerequisite for reperfusion. Their data support the premise that reperfusion is the more influential of the 2 parameters on both clinical and radiological outcomes. Cho et al analyzed a prospective database of patients with acute stroke studied with serial MR angiography, diffusion-weighted imaging (DWI), and bolus contrast perfusion imaging, on admission and 3 hours later. Forty-six patients were eligible for their study. The median volume of tissue at risk (perfusion lesion with T max >6 seconds–DWI lesion) was 13 mL, which is modest compared …

Wake-Up Stroke: Current Understanding.

Abstract Patients with wake-up strokes account for approximately 1 in 5 individuals presenting with an acute ischemic stroke. However, they are commonly excluded from acute stroke treatment. This article reviews the current understanding of wake-up strokes. A comparison of wake-up and awake-onset strokes demonstrated that they are physiologically, clinically, and radiologically similar. Use of advanced CT and MRI techniques may help extend acute stroke treatment options to patients with wake-up stroke.

Time From Imaging to Endovascular Reperfusion Predicts Outcome in Acute Stroke

Background and Purpose— This study aims to describe the relationship between computed tomographic (CT) perfusion (CTP)-to-reperfusion time and clinical and radiological outcomes, in a cohort of patients who achieve successful reperfusion for acute ischemic stroke. Methods— We included data from the CRISP (Computed Tomographic Perfusion to Predict Response in Ischemic Stroke Project) in which all patients underwent a baseline CTP scan before endovascular therapy. Patients were included if they had a mismatch on their baseline CTP scan and achieved successful endovascular reperfusion. Patients with mismatch were categorized into target mismatch and malignant mismatch profiles, according to the volume of their Tmax >10s lesion volume (target mismatch, <100 mL; malignant mismatch, >100 mL). We investigated the impact of CTP-to-reperfusion times on probability of achieving functional independence (modified Rankin Scale, 0–2) at day 90 and radiographic outcomes at day 5. Results— Of 156 included patients, 108 (59%) had the target mismatch profile, and 48 (26%) had the malignant mismatch profile. In patients with the target mismatch profile, CTP-to-reperfusion time showed no association with functional independence (P=0.84), whereas in patients with malignant mismatch profile, CTP-to-reperfusion time was strongly associated with lower probability of functional independence (odds ratio, 0.08; P=0.003). Compared with patients with target mismatch, those with the malignant mismatch profile had significantly more infarct growth (90 [49–166] versus 43 [18–81] mL; P=0.006) and larger final infarct volumes (110 [61–155] versus 48 [21–99] mL; P=0.001). Conclusions— Compared with target mismatch patients, those with the malignant profile experience faster infarct growth and a steeper decline in the odds of functional independence, with longer delays between baseline imaging and reperfusion. However, this does not exclude the possibility of treatment benefit in patients with a malignant profile.

Comparison of stroke volume evolution on diffusion-weighted imaging and fluid-attenuated inversion recovery following endovascular thrombectomy

Background To compare the evolution of the infarct lesion volume on both diffusion-weighted imaging and fluid-attenuated inversion recovery in the first five days after endovascular thrombectomy. Methods We included 109 patients from the CRISP and DEFUSE 2 studies. Stroke lesion volumes obtained on diffusion-weighted imaging and fluid-attenuated inversion recovery images both early post-procedure (median 18 h after symptom onset) and day 5, were compared using median, interquartile range, and correlation plots. Patients were dichotomized based on the time after symptom onset of their post procedure images (≥18 h vs. <18 h), and the degree of reperfusion (on Tmax>6 s; ≥ 90% vs. < 90%). Results Early post-procedure, median infarct lesion volume was 19 ml [(IQR) 7–43] on fluid-attenuated inversion recovery, and 23 ml [11–64] on diffusion-weighted imaging. On day 5, median infarct lesion volume was 52 ml [20–118] on fluid-attenuated inversion recovery, and 37 ml [16–91] on diffusion-weighted imaging. Infarct lesion volume on early post-procedure diffusion-weighted imaging, compared to fluid-attenuated inversion recovery, correlated better with day 5 diffusion-weighted imaging and fluid-attenuated inversion recovery lesions (r = 0.88 and 0.88 vs. 0.78 and 0.77; p < 0.0001). Median lesion growth was significantly smaller on diffusion-weighted imaging when the early post-procedure scan was obtained ≥18 h post stroke onset (5 ml [−1–13]), compared to <18 h (13 ml [2–47]; p = 0.03), but was not significantly different on fluid-attenuated inversion recovery (≥18 h: 26 ml [12–57]; <18 h: 21 ml [5–57]; p = 0.65). In the <90% reperfused group, the median infarct growth was significantly larger for diffusion-weighted imaging and fluid-attenuated inversion recovery (diffusion-weighted imaging: 23 ml [8–57], fluid-attenuated inversion recovery: 41 ml [13–104]) compared to ≥90% (diffusion-weighted imaging: 6 ml [2–24]; p = 0.003, fluid-attenuated inversion recovery: 19 ml [8–46]; p = 0.001). Conclusions Early post-procedure lesion volume on diffusion-weighted imaging is a better estimate of day 5 infarct volume than fluid-attenuated inversion recovery. However, both early post-procedure diffusion-weighted imaging and fluid-attenuated inversion recovery underestimate day 5 diffusion-weighted imaging and fluid-attenuated inversion recovery lesion volumes, especially in patients who do not reperfuse.