Kijeong Lee

Time-Dependent Thrombus Resolution After Tissue-Type Plasminogen Activator in Patients With Stroke and Mice

Background and Purpose— We investigated the relationship between the degree of thrombus resolution and the time from stroke onset or thrombus formation to intravenous tissue-type plasminogen activator (tPA) treatment. Methods— In patients with stroke, we measured thrombus volume on thin-section noncontrast brain computed tomographic scans taken at baseline and 1 hour after tPA administration. We determined the association between the time from symptom onset to tPA treatment and the degree of thrombus resolution. In a C57/BL6 mouse model of FeCl3-induced carotid artery thrombosis, we investigated the effect of tPA administered at different time intervals after thrombus formation, using Doppler-based blood flow measurement. Results— Of 249 patients enrolled, 171 showed thrombus on baseline computed tomography. Thrombus was resolved by ≥50% in 43 patients (25.1%, good volume reduction) and by <50% in 94 patients (55.0%, moderate volume reduction) 1 hour after tPA treatment. In 34 patients (19.9%, nonvolume reduction; either no change or thrombus volume increased), overall thrombus volume increased. The probability of thrombus resolution decreased as the time interval from symptom onset to treatment increased. On multivariate analysis, good volume reduction was independently related with shorter time intervals from symptom onset to tPA treatment (odds ratio, 0.986 per minute saved; 95% confidence interval, 0.974–0.999). In the mouse model, as the interval between thrombus formation and tPA treatment increased, the initiation of recanalization was delayed (P=0.006) and the frequency of final recanalization decreased (P for trends=0.006). Conclusions— Early administration of tPA after stroke onset is associated with better thrombus resolution.

Effect and Safety of Rosuvastatin in Acute Ischemic Stroke

Background and Purpose The benefit of statins in acute stroke remains uncertain. Statins may prevent stroke recurrence during the acute stage of stroke via pleiotropic effects. However, statins may increase the risk of intracerebral hemorrhage. We investigated the effect and safety of rosuvastatin in acute stroke patients. Methods This randomized, double-blind, multi-center trial compared rosuvastatin 20 mg and placebo in statin-naïve stroke patients who underwent diffusion-weighted imaging (DWI) within 48 hours after symptom onset. The primary outcome was occurrence of new ischemic lesions on DWI at 5 or 14 days. Results This trial was stopped early after randomization of 316 patients due to slow enrollment. Among 289 patients with at least one follow-up imaging, the frequency of new ischemic lesions on DWI was not different between groups (rosuvastatin: 27/137, 19.7% vs. placebo: 36/152, 23.6%) (relative risk 0.83, 95% confidence interval 0.53–1.30). Infarct volume growth at 5 days (log-transformed volume change, rosuvastatin: 0.2±1.0 mm3 vs. placebo: 0.3±1.3 mm3; P=0.784) was not different, either. However, hemorrhagic infarction or parenchymal/subarachnoid hemorrhage on gradient-recalled echo magnetic resonance imaging occurred less frequently in the rosuvastatin group (6/137, 4.4%) than the placebo group (22/152, 14.5%, P=0.007). Among 314 patients with at least one dose of study medication, progression or clinical recurrence of stroke tended to occur less frequently in the rosuvastatin group (1/155, 0.6% vs. 7/159, 4.4%, P=0.067). Adverse events did not differ between groups. Conclusions The efficacy of rosuvastatin in reducing recurrence in acute stroke was inconclusive. However, statin use was safe and reduced hemorrhagic transformation.

Value of utilizing both ASPECTS and CT angiography collateral score for outcome prediction in acute ischemic stroke.

Background Alberta Stroke Program Early CT Score (ASPECTS) represents the extent of irreversibly damaged tissue; while CT angiography collateral score (CTA-CS) denotes the degree of collaterals. Aims We investigated whether there is cumulative value in using both ASPECTS and CTA-CS for outcome prediction and attempted to determine the specific subgroup of patients who could benefit from successful reperfusion using these scores. Methods This is a retrospective observational study of stroke patients treated with intra-arterial reperfusion therapy for unilateral arterial occlusion in the anterior circulation. A favorable outcome was defined as modified Rankin Scale ≤ 2 at three-months. Receiver operating characteristic comparison analysis was performed to decide whether outcome predictability increases when ASPECTS and CTA-CS are used together. Classification and regression tree (CART) analysis was done to identify the variables that best predict outcome and define the specific subgroup of patients who could benefit from successful reperfusion. Results A total of 91 consecutive patients were included. Outcome predictability of ASPECTS with CTA-CS was better than that of ASPECTS (P = 0·088) or that of CTA-CS (P = 0·049). CART analysis revealed that ASPECTS > 5 was the primary determinant of favorable outcome, followed by CTA-CS > 1. Among 19 patients with ASPECTS ≤ 5, none had a favorable outcome. Successful reperfusion was associated significantly with favorable outcome in the 51 patients with ASPECTS > 5 and CTA-CS > 1, but not in the 21 patients with ASPECTS > 5 and CTA-CS ≤ 1. Conclusions Outcome predictability improves when using ASPECTS and CTA-CS together.

An Objective Pronator Drift Test Application (iPronator) Using Handheld Device

Background The pronator drift test is widely used to detect mild arm weakness. We developed an application that runs on a handheld device to objectify the pronator drift test and investigated its feasibility in stroke patients. Methods The iPronator application, which uses the built-in accelerometer in handheld devices, was developed. We enrolled acute ischemic stroke patients (n = 10) with mild arm weakness and healthy controls (n = 10) to validate the iPronator. In addition to conventional neurological examinations, the degree of average, maximum, and oscillation in drift and pronation were measured and compared using the iPronator. Follow-up tests using the iPronator were also conducted in the patient group one week later. Results There was a strong correlation between the average degree of pronation and drift measured by the iPronator (r = 0.741, p<0.001). The degrees of average and maximum in pronation were greater in the patient group than in the control group [in average, 28.9°, interquartile range (IQR) 18.7–40.3 vs. 3.8° (IQR 0.3–7.5), p<0.001], in maximum, 33.0° (IQR 24.0–52.1) vs. 6.2° (IQR 1.4–9.4), p<0.001]. The degree of oscillation in pronation was not different between the groups (p = 0.166). In drift, the degrees of average, maximum, and oscillation were greater in the patient group. In stroke patients, a follow-up study at one week revealed improvements in the degrees of pronation and drift compared with baseline parameters. Conclusions The iPronator can reliably detect mild arm weakness of stroke patients and was also useful in detecting functional recovery for one week in patients with acute stroke.

Factors Associated with Early Hospital Arrival in Patients with Acute Ischemic Stroke

Background and Purpose Factors associated with early arrival may vary according to the characteristics of the hospital. We investigated the factors associated with early hospital arrival in two different stroke centers located in Korea and Japan. Methods Consecutive patients with ischemic stroke arrived hospital within 48 hours of onset between January 2011 and December 2012 were identified and the clinical and time variables were retrieved from the prospective stroke registries of Severance Hospital of Yonsei University Health System (YUHS; Seoul, Korea) and National Cerebral and Cardiovascular Center (NCVC; Osaka, Japan). Subjects were dichotomized into early (time from onset to arrival ≤4.5 hours) and late (>4.5 hours) arrival groups. Univariate and multivariate analyses were performed to evaluate factors associated with early hospital arrival. Results A total of 1,966 subjects (992 from YUHS; 974 from NCVC) were included in this study. The median time from onset to arrival was 6.1 hours [interquartile range, 1.7-17.8 hours]. In multivariate analysis, the factors associated with early arrival were atrial fibrillation (Odds ratio [OR], 1.505; 95% confidence interval [CI], [1.168-1.939]), higher initial National Institute of Health Stroke Scale scores (OR, 1.037; 95% CI [1.023-1.051]), onset during daytime (OR, 2.799; 95% CI [2.173-3.605]), and transport by an emergency medical service (OR, 2.127; 95% CI [1.700-2.661]). These factors were consistently associated with early arrival in both hospitals. Conclusions Despite differences between the hospitals, there were common factors related to early arrival. Efforts to identify and modify these factors may promote early hospital arrival and improve stroke outcome.

Comparison of Outcomes after Reperfusion Therapy between In-Hospital and Out-of-Hospital Stroke Patients

Background: Patients may experience stroke while being admitted to the hospital (in-hospital stroke (IHS)) and they may be important candidates for reperfusion therapy. IHS patients may have various comorbidities and show worse outcomes compared with patients with an out-of-hospital stroke (OHS). On the other hand, the time from onset to treatment may be shorter in IHS patients than OHS patients. Most outcome studies of reperfusion therapy have been based on findings in OHS patients, and little information is currently available regarding outcomes of IHS, whether the outcomes differ between patients with IHS and those with OHS who receive reperfusion therapy. Methods: This is a retrospective observational study using prospectively registered data. Consecutive patients who underwent the reperfusion therapy (intravenous (IV), intra-arterial (IA), or combined IV and IA) between July 2002 and June 2014 in a university hospital were included for this study. We compared the demographics, time interval from symptom onset to treatment, and outcomes between IHS and OHS patients and analyzed the factors associated with in-hospital mortality. Results: A total of 686 patients received the reperfusion therapy during the study period. Of them, 256 (37.3%) patients received the IV tissue plasminogen activator (t-PA) therapy only, 243 (35.4%) patients received the IA therapy only, and 187 (27.3%) patients received the combined IV and IA therapy. Among these, 104 (15.2%) were IHS patients. The time intervals from symptom onset to IV t-PA administration (87.5 ± 48.4 vs. 113.4 ± 38.3 min, p < 0.001) and IA puncture (221.8 ± 195.0 vs. 343.6 ± 155.4 min, p < 0.001) were shorter for IHS than OHS. The rates of successful recanalization and symptomatic intracerebral hemorrhage, and the favorable functional outcome at 3 months were similar between the groups. In-hospital all-cause mortality was higher in IHS than OHS (16.3 vs. 8.4%, p = 0.019), but after adjustment, IHS was not an independent factor. The stroke mortality did not differ between the groups (9.6 vs. 6.9%, p = 0.432). Conclusions: Although IHS patients more frequently had comorbid diseases and higher overall in-hospital mortality, the standard outcomes of the reperfusion therapy were similar between IHS and OHS patients, which might be, in part, ascribed to the shorter interval from symptom onset to treatment in IHS. Considering a substantial portion of IHS patients, we should pay more attention to these patients.

Decision-making support using a standardized script and visual decision aid to reduce door-to-needle time in stroke

배경: 뇌졸중에서 정맥 내 조직플라스미노겐활성인자의 빠른 투여는 혈전용해 효과를 강화시키는 효과적인 방법이다. 환자와 보호자가 치료에 대한 의사 결정을 내리는 과정이 치료가 지연되는 원인이 될 수 있다. 본 연구는 급성기 뇌졸중 환자에서 환자와 보호자에게 의사결정 지원 프로토콜이 병원 도착부터 혈전용해제 ...

D-dimer for prediction of long-term outcome in cryptogenic stroke patients with patent foramen ovale

Patent foramen ovale (PFO) is a potential cause of cryptogenic stroke, given the possibility of paradoxical embolism from venous to systemic circulation. D-dimer level is used to screen venous thrombosis. We investigated the risk of embolism and mortality according to the presence of PFO and D-dimer levels in cryptogenic stroke patients. A total of 570 first-ever cryptogenic stroke patients who underwent transesophageal echocardiography were included in this study. D-dimer was assessed using latex agglutination assay during admission. The association of long-term outcomes with the presence of PFO and D-dimer levels was investigated. PFO was detected in 241 patients (42.3 %). During a mean 34.0 ± 22.8 months of follow-up, all-cause death occurred in 58 (10.2 %) patients, ischaemic stroke in 33 (5.8 %), and pulmonary thromboembolism in 6 (1.1 %). Multivariate Cox regression analysis showed that a D-dimer level of > 1,000 ng/ml was an independent predictor for recurrent ischaemic stroke in patients with PFO (hazard ratio 5.341, 95 % confidence interval 1.648-17.309, p=0.005), but not in those without PFO. However, in patients without PFO, a D-dimer level of > 1,000 ng/ml was independently related with all-cause mortality. The risk of pulmonary thromboembolism tended to be high in patients with high D-dimer levels, regardless of PFO. Elevated D-dimer levels in cryptogenic stroke were predictive of the long-term outcome, which differed according to the presence of PFO. The coexistence of PFO and a high D-dimer level increased the risk of recurrent ischaemic stroke. The D-dimer test in cryptogenic stroke patients may be useful for predicting outcomes and deciding treatment strategy.

Increased Risk of Cardiovascular Events in Stroke Patients Who had Not Undergone Evaluation for Coronary Artery Disease

Purpose Although asymptomatic coronary artery occlusive disease is common in stroke patients, the long-term advantages of undergoing evaluation for coronary arterial disease using multi-detector coronary computed tomography (MDCT) have not been well established in stroke patients. We compared long-term cardio-cerebrovascular outcomes between patients who underwent MDCT and those who did not. Materials and Methods This was a retrospective study in a prospective cohort of consecutive ischemic stroke patients. Of the 3117 patients who were registered between July 2006 and December 2012, MDCT was performed in 1842 patients [MDCT (+) group] and not in 1275 patients [MDCT (−) group]. Occurrences of death, cardiovascular events, and recurrent stroke were compared between the groups using Cox proportional hazards models and propensity score analyses. Results During the mean follow-up of 38.0±24.8 months, 486 (15.6%) patients died, recurrent stroke occurred in 297 (9.5%), and cardiovascular events occurred in 60 patients (1.9%). Mean annual risks of death (9.34% vs. 2.47%), cardiovascular events (1.2% vs. 0.29%), and recurrent stroke (4.7% vs. 2.56%) were higher in the MDCT (−) group than in the MDCT (+) group. The Cox proportional hazards model and the five propensity score-adjusted models consistently demonstrated that the MDCT (−) group was at a high risk of cardiovascular events (hazard ratios 3.200, 95% confidence interval 1.172–8.735 in 1:1 propensity matching analysis) as well as death. The MDCT (−) group seemed to also have a higher risk of recurrent stroke. Conclusion Acute stroke patients who underwent MDCT experienced fewer deaths, cardiovascular events, and recurrent strokes during follow-up.

Lenticulostriate Artery Involvement is Predictive of Poor Outcomes in Superficial Middle Cerebral Artery Territory Infarction

Purpose Patients with superficial middle cerebral artery (MCA) territory infarction may have concomitant lenticulostriate artery (LSA) territory infarction. We investigated the mechanisms thereof and the outcomes of patients with superficial MCA territory infarction according to the presence or absence of LSA involvement. Materials and Methods Consecutive patients with first-ever infarction in the unilateral superficial MCA territory were included in this study. They were divided into the superficial MCA only (SM) group and the superficial MCA plus LSA (SM+L) group. Results Of the 398 patients, 84 patients (21.1%) had LSA involvement (SM+L group). The SM+L group more frequently had significant stenosis of the proximal MCA or carotid artery and high-risk cardioembolic sources. Stroke severity and outcomes were remarkably different between the groups. The SM+L group showed more severe neurologic deficits (National Institute of Health Stroke Scale score 10.8±7.1 vs. 4.0±5.0, p<0.001) and larger infarct in the superficial MCA territory (40.8±62.6 cm3 vs. 10.8±21.8 cm3, p<0.001) than the SM group. A poor functional outcome (mRS >2) at 3 months was more common in the SM+L group (64.3% vs. 15.9%, p<0.001). During a mean follow-up of 26 months, 67 patients died. All-cause (hazard ratio, 2.246) and stroke (hazard ratio, 9.193) mortalities were higher in the SM+L group than the SM group. In multivariate analyses, LSA involvement was an independent predictor of poor functional outcomes and stroke mortality. Conclusion LSA territory involvement is predictive of poor long-term outcomes in patients with superficial MCA territory infarction.