Jong Yun Lee

A new subtype classification of ischemic stroke based on treatment and etiologic mechanism.

A new subtype classification of ischemic stroke was developed to reflect recent therapeutic strategies as well as evolving concepts of stroke definitions and mechanisms. In 200 consecutive patients with acute ischemic stroke, the inter-rater reliability and proportion of subtypes of the new classification system were assessed and compared with those of the Trial of ORG 10172 in the Acute Stroke Treatment (TOAST) classification. The most frequent subtype of the new classification was atherothrombosis (n = 80, 40%), followed by stroke of undetermined etiology (n = 54, 27%), small artery disease (n = 33, 16.5%), cardioembolism (n = 26, 13%), and stroke of other determined etiology (n = 7, 3.5%). Three raters agreed to the stroke subtype diagnosis in 165 out of 200 cases and the overall ĸ value was excellent (ĸ = 0.82). The new classification system for brain infarction was easy to use and had high inter-rater reliability.

Improved Time Intervals by Implementation of Computerized Physician Order Entry-Based Stroke Team Approach

Background: The need for rapid evaluation and treatment of acute stroke patients has been well documented. A computerized physician order entry (CPOE) system can improve communication and provide immediate access to information, which may be useful for an effective team approach program targeted to reduce in-hospital time delays. Methods: To reduce the time from a patient’s arrival at the emergency department to thrombolysis, a team approach program using CPOE was developed, and its efficacy was investigated by comparing time intervals from arrival to evaluation and intravenous tissue-type plasminogen activator (tPA) treatment before and after the implementation of the program. Results: Among 379 consecutive patients who were screened as potential candidates for thrombolysis, 25 patients (6.6%) received tPA during a 1-year period after initiation of the program. Fourteen patients were treated with tPA in the previous year. After program implementation, time from arrival to computed tomography scan was reduced from 34 to 19 min (p = 0.01). Time to report of complete blood count was also shortened from 52 to 33 min (p < 0.01). Finally, time from arrival to tPA treatment was reduced by 23 min (from 79 to 56 min; p < 0.01). Onset-to-door time tended to be longer after the program implementation (from 41 to 60 min; p = 0.14). Conclusions: Implementation of the CPOE-based team approach program significantly reduced time from emergency department arrival to evaluations and treatment.

Frequency and Significance of Cardiac Sources of Embolism in the TOAST Classification

Background: This study was aimed at determining the frequency and coexistent patterns of high- and medium-risk cardiac sources of embolism (CSE) as defined by the Trial of ORG 10172 in the Acute Stroke Treatment (TOAST) classification system and at investigating how identified CSE contributed to this classification. Methods: We analyzed data from 2,482 patients with acute cerebral infarctions who registered in the Yonsei Stroke Registry over a 10-year period. Cardiac sources were divided into high- and medium-risk groups based on the TOAST classification. Results: Of the 2,482 patients, 1,130 (46%) underwent echocardiographic studies. At least one CSE was detected in 629 patients (25%). Atrial fibrillation was the most common high-risk CSE. Patent foramen ovale, spontaneous echo contrast and congestive heart failure comprised most of the medium-risk CSE. Atrial fibrillation frequently accompanied coexistent CSE (69%) such as spontaneous echo contrast, congestive heart failure, and left atrial/appendage thrombus, while patent foramen ovale was detected in isolation in more than 90% of the patients. Patients with a high-risk CSE were more likely to be diagnosed with cardioembolism (83%) than patients with only a medium-risk CSE (58%). Conclusions: Our study elucidated the frequency and various coexistent patterns of CSE in Korean stroke patients as defined by the TOAST classification system. In addition, we have demonstrated a higher correlation between high-risk CSE and cardioembolism than with medium-risk CSE and cardioembolism.

Association of aortic plaque with intracranial atherosclerosis in patients with stroke

Objective: To determine whether there is a relationship between aortic plaques and intracranial (IC) atherosclerosis. Methods: We reviewed 922 patients with stroke who had both transesophageal echocardiography and cerebral angiography. The plaques of these patients were classified as either complex aortic plaques (CAP), which protruded ≥4 mm or were present as mobile lesions in the proximal aorta, or simple aortic plaques (SAP), which were <4 mm or present in the descending aorta. Cerebral artery atherosclerosis was classified as either an IC or extracranial (EC) atherosclerosis. Results: Among the 922 patients, we found aortic plaques in 237 patients (26%). There were 111 (47%) patients of SAP, 74 (31%) patients with CAP, and 52 (22%) patients that had both SAP and CAP. Angiography showed IC or EC atherosclerosis in 511 patients (55%). The presence of aortic plaques was significantly associated with IC or EC atherosclerosis. The significance appeared to be due to the strong association between the presence of SAP and IC atherosclerosis (51% SAP vs 35% no plaques; odds ratio = 1.94, 95% CI: 1.17 to 3.21). In the multiple logistic regression analysis, SAP were independent predictors of IC atherosclerosis Conclusions: The presence of simple aortic plaques may be a marker of advanced vascular disease. Detection of simple aortic plaques during transesophageal echocardiography may have clinical implications because patients with these plaques frequently had concomitant intracranial atherosclerosis, a risk factor for stroke.

Prediction of long-term outcome by percent improvement after the first day of thrombolytic treatment in stroke patients

BACKGROUND We investigated a method for assessing early improvement and predictive factors of early and late outcomes in patients receiving thrombolytic therapy. METHODS A total of 160 consecutive patients who received thrombolytic therapy were included in the study. Using National Institutes of Health Stroke Scale (NIHSS) scores, percent improvement [(baseline NIHSS score-24-hour NIHSS score)/baseline NIHSS score x 100] was calculated and compared with delta (baseline NIHSS score-24-hour NIHSS score) and with major neurological improvement (MNI, NIHSS score of 0-1 or >or=8 point improvement at 24 h) by receiver operating characteristic (ROC) curve analysis. Finally, we investigated the independent predictors of improvement at 24 h after the thrombolytic therapy and of favorable 3-month outcome (modified Rankin scale score 0-2). RESULTS By pairwise comparison of ROC curves, percent improvement was stronger than delta (p=0.004) and MNI (p<0.001) in predicting long-term outcome. First day improvement (FDI), defined as greater than 20% improvement, was a strong predictor of favorable 3-month outcome (OR 12.55, 95% CI 5.41-29.10). Recanalization (OR 3.30, 95% CI 1.28-8.45), absence of carotid T occlusion (OR 0.09, 95% CI 0.02-0.42) and hemorrhagic transformation (OR 0.25, 95% CI 0.09-0.73) were independent predictors of FDI. Independent predictors of favorable 3-month outcome were FDI, current smoking, absence of carotid T occlusion and hemorrhagic transformation. CONCLUSIONS Percent improvement at 24 h after thrombolytic therapy is a useful surrogate marker for predicting the long-term outcome. Our findings highlight the importance of early stroke management.

Post-transfusion posterior leukoencephalopathy with cytotoxic and vasogenic edema precipitated by vasospasm.

Introduction The syndrome of posterior leukoencephalopathy (PLE) is characterized clinically by headache, vomiting, confusion, seizures, visual abnormalities, and motor signs in association with mainly posterior lesions, which suggest edema on neuroimages [1]. PLE has often been associated with various, usually systemic disorders, such as hypertensive encephalopathy, eclampsia, and the use of immunosuppressive drugs. Ito et al. [2] reported upon a patient with transfusion-related reversible PLE and angiographic evidence of vasoconstriction. It is not certain whether the mechanism of edema formation in PLE is disruption of the blood-brain barrier and fluid extravasation, or an ischemic process induced by vasospasm. Diffusion-weighted magnetic resonance imaging (DWI) can discriminate between cytotoxic and vasogenic edema and provides a clue to the mechanism of PLE [3–6]. We describe a patient with post-transfusion PLE who showed vasospasm and features suggesting cytotoxic and vasogenic edema on DWI.

Effect of cilostazol in acute lacunar infarction based on pulsatility index of transcranial Doppler (ECLIPse): a multicenter, randomized, double-blind, placebo-controlled trial.

Background: This study is intended to evaluate the propensities of cilostazol to reduce the pulsatility index (PI) in patients with acute lacunar infarction using the serial transcranial Doppler (TCD) examinations. Methods: In a multicenter, randomized, double-blind, placebo-controlled trial, patients were randomly assigned to receive either placebo or 100 mg cilostazol twice a day as well as aspirin 100 mg a day. The primary outcomes were the changes of middle cerebral artery (MCA) and basilar artery (BA) PIs at 14 and 90 days from the baseline TCD study. This study is registered with ClinicalTrials.gov (NCT00741286). Results: Trial medication was given to 203 patients, with 100 receiving cilostazol and 103 receiving placebo, and 164 were included in the per-protocol analysis of the primary outcome. Results from the linear mixed model showed that significant effects were obtained for time-by-group interactions (p = 0.008 in right MCA, p = 0.015 in left MCA, p = 0.002 in BA), suggesting that changes of PIs from the baseline to the 90-day study were different across the groups. Conclusions: Cilostazol further decreased TCD PIs at 90 days from baseline compared to placebo in acute lacunar infarction. This result may be related to pleiotropic effects, such as vasodilation, beyond its antiplatelet activity.

Preconditioning with Chronic Cerebral Hypoperfusion Reduces a Focal Cerebral Ischemic Injury and Increases Apurinic/Apyrimidinic Endonuclease/Redox Factor-1 and Matrix Metalloproteinase-2 Expression

Atherosclerosis may cause severe stenosis of the arteries supplying the brain, which induces chronic cerebral hypoperfusion. Although an infarction often occurs in the chronically hypoperfused brain area, it has been uncertain whether the stroke severity is attenuated or increased when further decrease of blood flow occurs. To test the hypothesis that chronic cerebral hypoperfusion is protective against the subsequent severe ischemia, we examined the effect of chronic cerebral hypoperfusion on brains subjected to acute focal ischemia. Spontaneous hypertensive rats were subjected to middle cerebral artery occlusion/reperfusion four weeks after bilateral common carotid artery ligation (BCAL) or sham operation. The rats with BCAL had smaller infarctions, determined by 2,3,5-triphenyltetrazolium hydrochloride staining, and less severe neurologic deficits than those with sham operation. The number of DNA-damaged cells, examined by the in situ nick translation study, was significantly reduced in animals with BCAL. Immunoreactivity for apurinic/apyrimidinic endonuclease/redox factor-1, which plays a role in cellular defense mechanism, was markedly increased in those with BCAL. Indirect evidence of extracellular matrix remodeling, which might be associated with adaptive arteriogenesis or angiogenesis, was obtained in the form of increased matrix metalloproteinase-2 activity in them. These findings provide experimental evidence that chronic cerebral hypoperfusion would be protective against subsequent severe ischemic insults.

Cilostazol decreases cerebral arterial pulsatility in patients with mild white matter hyperintensities: subgroup analysis from the Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of Transcranial Doppler (ECLIPse) study.

Background: The Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of the Transcranial Doppler (ECLIPse) study showed a significant decrease in the transcranial Doppler (TCD) pulsatility index (PI) with cilostazol treatment at 90 days after acute lacunar infarction. The aim of the present study was to perform a subgroup analysis of the ECLIPse study in order to explore the effect of cilostazol in acute lacunar infarction based on cerebral white matter hyperintensities (WMH) volume. Methods: The ECLIPse study was a multicenter, randomized, double-blind, placebo-controlled trial that evaluated the difference between the efficacy of cilostazol and a placebo to reduce the PI in patients with acute lacunar infarction using serial TCD examinations. The primary outcome was changes in the PIs of the middle cerebral artery (MCA) and basilar artery at 14 and 90 days from the baseline TCD study. For this subgroup analysis, using semi-automated computerized software, the WMH volume was measured for those subjects for whom fluid-attenuated inversion recovery (FLAIR) images were available. Results: Of the 203 patients in eight hospitals in the ECLIPse study, 130 participants from six hospitals were included in this subgroup analysis. Cilostazol was given to 63 patients (48.5%) and placebo to 67 patients (51.5%). All baseline characteristics were well balanced across the two groups, and there were no significant differences in these characteristics except in the changes of PI from the baseline to the 90-day point. There was a significant decrease of TCD PIs at 90-day study from baseline in the cilostazol group (p = 0.02). The mean WMH volume was 11.57 cm3 (0.13-68.45, median 4.86) and the mean MCA PI was 0.95 (0.62-1.50). The changes in PIs from the baseline to 14 days and to 90 days were 0.09 (-0.21 to 0.33) and 0.10 (-0.22 to 0.36). While there were no significant correlations between WMH volume and the changes in PIs, a trend of inverse correlation was observed between the WMH volume and the changes in PIs from the baseline to the 90-day point. For the subgroup analysis, the WMH volume was dichotomized based on its median value (4.90 cm3). Cilostazol decreased the TCD PIs significantly at the 90-day point in patients with WMH volumes ≤4.9 cm3 (p = 0.002). Significant treatment effects were observed in the cilostazol group. Conclusions: This study showed that cilostazol decreased cerebral arterial pulsatility in patients with WMH. Our findings indicate the unique effect of cilostazol in small vessel disease (SVD), especially in patients with mild WMH changes. Further clinical trials focusing on WMH volume and clinical outcomes are required to assess the unique efficacy of cilostazol in SVD.

Factors Associated with Ischemic Stroke on Therapeutic Anticoagulation in Patients with Nonvalvular Atrial Fibrillation

Purpose In this study, we investigated the stroke mechanism and the factors associated with ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF) who were on optimal oral anticoagulation with warfarin. Materials and Methods This was a multicenter case-control study. The cases were consecutive patients with NVAF who developed cerebral infarction or transient ischemic attack (TIA) while on warfarin therapy with an international normalized ratio (INR) ≥2 between January 2007 and December 2011. The controls were patients with NVAF without ischemic stroke who were on warfarin therapy for more than 1 year with a mean INR ≥2 during the same time period. We also determined etiologic mechanisms of stroke in cases. Results Among 3569 consecutive patients with cerebral infarction or TIA who had NVAF, 55 (1.5%) patients had INR ≥2 at admission. The most common stroke mechanism was cardioembolism (76.0%). Multivariate analysis demonstrated that smoking and history of previous ischemic stroke were independently associated with cases. High CHADS2 score (≥3) or CHA2DS2-VASc score (≥5), in particular, with previous ischemic stroke along with ≥1 point of other components of CHADS2 score or ≥3 points of other components of CHA2DS2-VASc score was a significant predictor for development of ischemic stroke. Conclusion NVAF patients with high CHADS2/CHA2DS2-VASc scores and a previous ischemic stroke or smoking history are at high risk of stroke despite optimal warfarin treatment. Some other measures to reduce the risk of stroke would be necessary in those specific groups of patients.