Differences in Therapeutic Responses and Factors Affecting Post-Stroke Depression at a Later Stage According to Baseline Depression

Lee, Eun-Jae,Kim, Jong S.,Chang, Dae-Il,Park, Jong-Ho,Ahn, Seong Hwan,Cha, Jae-Kwan,Heo, Ji Hoe,Sohn, Sung-Il,Lee, Byung-Chul,Kim, Dong-Eog,Kim, Hahn Young,Kim, Seongheon,Kwon, Do-Young,Kim, Jei,Seo, Korean Stroke Society 2018 Journal of stroke Vol.20 No.2

<P><B>Background and Purpose</B></P><P> The pathophysiology of post-stroke depression (PSD) is complex and may differ according to an individual’s mood immediately after stroke. Here, we compared the therapeutic response and clinical characteristics of PSD at a later stage between patients with and without depression immediately after stroke. </P><P><B>Methods</B></P><P> This study involved a <I>post hoc</I> analysis of data from EMOTION (ClinicalTrials.gov NCT01278498), a placebo-controlled, double-blind trial that examined the efficacy of escitalopram (10 mg/day) on PSD and other emotional disturbances among 478 patients with acute stroke. Participants were classified into the Baseline-Blue (patients with baseline depression at the time of randomization, defined per the Montgomery-Asberg Depression Rating Scale [MADRS] ≥8) or the Baseline-Pink groups (patients without baseline depression). We compared the efficacy of escitalopram and predictors of 3-month PSD (MADRS ≥8) between these groups. </P><P><B>Results</B></P><P> There were 203 Baseline-Pink and 275 Baseline-Blue patients. The efficacy of escitalopram in reducing PSD risk was more pronounced in the Baseline-Pink than in the Baseline-Blue group (<I>p</I> for interaction=0.058). Several risk factors differentially affected PSD development based on the presence of baseline depression (<I>p</I> for interaction <0.10). Cognitive dysfunction was an independent predictor of PSD in the Baseline-Blue, but not in the Baseline-Pink group, whereas the non-use of escitalopram and being female were more strongly associated with PSD in the Baseline-Pink group. </P><P><B>Conclusions</B></P><P> Responses to escitalopram and predictors of PSD 3 months following stroke differed based on the presence of baseline depression. Our data suggest that PSD pathophysiology is heterogeneous; therefore, different therapeutic strategies may be needed to prevent PSD emergence following stroke.</P>

Prognostic Significance of Troponin Elevation for Long-Term Mortality after Ischemic Stroke

Ahn, Sung-Ho,Lee, Ji-Sung,Kim, Young-Hak,Kim, Bum Joon,Kim, Yeon-Jung,Kang, Dong-Wha,Kim, Jong S.,Kwon, Sun U. Korean Stroke Society 2017 Journal of stroke Vol.19 No.3

<P><B>Background and Purpose</B></P><P> Troponin, a marker of myocardial injury, frequently increases and is related with poor outcome in ischemic stroke patients. However, the long-term outcome of this elevation remains uncertain. We, therefore, investigated the prognostic significance of troponin elevation for long-term mortality, and explored factors affecting troponin elevation after ischemic stroke.</P><P><B>Methods</B></P><P> We retrospectively analyzed the medical data of stroke patients who were admitted within 24 hours of symptom onset and underwent a serum cardiac troponin I test at admission during a five-year period. Information on mortality as the outcome was obtained from the National Death Certificate system.</P><P><B>Results</B></P><P> A total of 1,692 patients were eligible for inclusion with 33 months of median follow-up. Troponin elevation that exceeded the 99th percentile (>0.04 ng/mL) of values was detected in 166 patients (9.8%). After adjusting for baseline characteristics, troponin elevation was associated with previous ischemic heart disease and congestive heart failure, comorbid atrial fibrillation and active cancer, and increased National Institutes of Health Stroke Scale score. Patients with troponin elevation had a high risk of overall death (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.40–2.40), including stroke-related (HR 1.71, 95% CI 1.14–2.55), cardiac-related (HR 3.17, 95% CI 1.49–6.74), and cancer-related (HR 1.98, 95% CI 1.14–3.45) death than those without troponin elevation.</P><P><B>Conclusions</B></P><P> Troponin elevation in the acute stage of ischemic stroke was associated with long-term mortality, mainly due to increased stroke- and cancer-related death in the first year and cardiacrelated death in the later period.</P>

Low Plasma Proportion of Omega 3-Polyunsaturated Fatty Acids Predicts Poor Outcome in Acute Non-Cardiogenic Ischemic Stroke Patients

Song, Tae-Jin,Cho, Hyun-Ji,Chang, Yoonkyung,Choi, Kyungsun,Jung, A-Reum,Youn, Minjung,Shin, Min-Jeong,Kim, Yong-Jae Korean Stroke Society 2015 Journal of stroke Vol.17 No.2

<P><B>Background and Purpose</B></P><P>Alterations in blood fatty acid (FA) composition are associated with cardiovascular diseases. We investigated whether plasma FA composition was related to stroke severity and functional outcome in acute ischemic stroke patients.</P><P><B>Methods</B></P><P>We prospectively enrolled 156 patients with first-episode cerebral infarction, within 7 days of symptom onset. The proportion of FAs was analyzed using gas chromatography, and the summation of the omega-3 polyunsaturated fatty acids (ω3-PUFA), 18:3 ω3 α-linolenic acid, 20:3 ω3 eicosatrienoic acid, 20:5 ω3 eicosapentaenoic acid (EPA), and 22:6 ω3 docosahexaenoic acid (DHA) was reported as Σω3-PUFAs. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score on admission. Poor functional outcome was defined by modified Rankin scale (mRS) ≥3 at three months after the index stroke.</P><P><B>Results</B></P><P>Lower proportions of EPA (β=-0.751), DHA (β=-0.610), and Σω3-PUFAs (β=-0.462) were independently associated with higher NIHSS score, after adjusting for stroke subtype, hemoglobin, high density lipoprotein, high sensitivity C-reactive protein, fasting glucose, 16:0 palmitic acid, and Σsaturated fatty acids. Moreover, a lower proportion of DHA (odds ratio [OR]: 0.20, 95% confidence interval [CI]: 0.04-0.88), and Σω3-PUFAs (OR: 0.22, 95% CI: 0.05-0.84) showed an independent relationship with poor functional outcome after adjusting for age, sex, smoking status, NIHSS score, stroke subtype, and 16:0 palmitic acid.</P><P><B>Conclusions</B></P><P>Our results demonstrate that ω3-PUFAs correlated with stroke severity on admission and functional outcomes at 3 months. ω3-PUFAs are potential blood biomarkers for prognosis of acute non-cardiogenic ischemic stroke patients.</P>

Updates on Prevention of Cardioembolic Strokes

Topcuoglu, Mehmet Akif,Liu, Liping,Kim, Dong-Eog,Gurol, M. Edip Korean Stroke Society 2018 Journal of stroke Vol.20 No.2

<P>Cardiac embolism continues to be a leading etiology of ischemic strokes worldwide. Although pathologies that result in cardioembolism have not changed over the past decade, there have been significant advances in the treatment and stroke prevention methods for these conditions. Atrial fibrillation remains the prototypical cause of cardioembolic strokes. The availability of new long-term monitoring devices for atrial fibrillation detection such as insertable cardiac monitors has allowed accurate detection of this leading cause of cardioembolism. The non-vitamin K antagonist oral anticoagulants have improved our ability to prevent strokes for many patients with non-valvular atrial fibrillation (NVAF). Advances in left atrial appendage closure and the U.S. Food and Drug Administration approval of the WATCHMAN (Boston Scientific) device for stroke prevention in NVAF patients who have an appropriate rationale for a nonpharmacological alternative, have revolutionized the field and provided a viable option for patients at higher hemorrhagic risk. The role of patent foramen ovale closure for secondary prevention in selected patients experiencing cryptogenic ischemic strokes at a relatively young age has become clearer thanks to the very recent publication of long-term outcomes from three major studies. Advances in the management of infective endocarditis, heart failure, valvular diseases, and coronary artery disease have significantly changed the management of such patients, but have also revealed new concerns related to assessment of ischemic versus hemorrhagic risk in the setting of antithrombotic use. The current review article aims to discuss these advances especially as they pertain to the stroke neurology practice.</P>

Effects of Triflusal and Clopidogrel on the Secondary Prevention of Stroke Based on Cytochrome P450 2C19 Genotyping

Han, Sang Won,Kim, Yong-Jae,Ahn, Seong Hwan,Seo, Woo-Keun,Yu, Sungwook,Oh, Seung-Hun,Nam, Hyo Suk,Choi, Hye-Yeon,Yoon, Sung Sang,Kim, Seo Hyun,Lee, Jong Yun,Lee, Jun Hong,Hwang, Yang-Ha,Lee, Kee Ook,J Korean Stroke Society 2017 Journal of stroke Vol.19 No.3

<P><B>Background and Purpose</B></P><P> To compare the efficacy and safety of antiplatelet agents for the secondary prevention of ischemic stroke based on cytochrome P450 2C19 (CYP2C19) polymorphisms. </P><P><B>Methods</B></P><P> This study was a prospective, multicenter, randomized, parallel-group, open-label, blind genotype trial. First time non-cardiogenic ischemic stroke patients were enrolled and screened within 30 days. Participants were randomized to receive either triflusal or clopidogrel for secondary stroke prevention. The primary outcome was the time from randomization to first recurrent ischemic stroke or hemorrhagic stroke. </P><P><B>Results</B></P><P> The required sample size was 1,080 but only 784 (73%) participants were recruited. In patients with a poor CYP2C19 genotype for clopidogrel metabolism (n=484), the risk of recurrent stroke among those who received triflusal treatment was 2.9% per year, which was not significantly different from those who received clopidogrel treatment (2.2% per year; hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.60–2.53). In the clopidogrel treatment group (n=393), 38% had good genotypes and 62% poor genotypes for clopidogrel metabolism. The risk of recurrent stroke in patients with a good CYP2C19 genotype was 1.6% per year, which was not significantly different from those with a poor genotype (2.2% per year; HR, 0.69; 95% CI, 0.26–1.79). </P><P><B>Conclusions</B></P><P> Whilst there were no significant differences between the treatment groups in the rates of stroke recurrence, major vascular events, or coronary revascularization, the efficacy of antiplatelet agents for the secondary prevention of stroke according to CYP2C19 genotype status remains unclear.</P>

Medical Treatment of Intracranial Atherosclerosis: An Update

Kim, Jong S.,Bang, Oh Young Korean Stroke Society 2017 Journal of stroke Vol.19 No.3

<P>For patients with symptomatic intracranial atherosclerosis (ICAS), antithrombotic agents are the mainstay of therapy. Anticoagulation (warfarin) is not widely used since it is not more effective than aspirin and carries a high risk of bleeding. New oral anticoagulants are showing promise, but their use has not been investigated in appropriate clinical trials. Since the recurrent stroke risk is high with aspirin monotherapy, dual antiplatelets are considered in the early stage of symptomatic ICAS. Based on the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) and Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) results, aspirin plus clopidogrel has been recommended. However, this combination was not superior to aspirin monotherapy in patients with ICAS in the CHANCE substudy. Progression of ICAS is common, and it is associated with recurrent strokes. In the Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis (TOSS) study, aspirin plus cilostazol was more effective than aspirin monotherapy in preventing progression. The TOSS II trial showed that the overall change in stenosis was better with aspirin plus cilostazol than with aspirin plus clopidogrel. Aside from antithrombotic therapy, risk factor management is critical for secondary prevention, and high blood pressure is clearly linked to recurrent stroke. However, blood pressure may have to be cautiously managed in the early stage of stroke. Considering that ICAS is the major cause of stroke worldwide, further investigations are needed to establish optimal management strategies for patients with ICAS.</P>

Estimation of Acute Infarct Volume with Reference Maps: A Simple Visual Tool for Decision Making in Thrombectomy Cases

Kim, Dong-Eog,Ryu, Wi-Sun,Schellingerhout, Dawid,Jeong, Han‐,Gil,Kim, Paul,Jeong, Sang-Wuk,Park, Man-Seok,Choi, Kang-Ho,Kim, Joon-Tae,Kim, Beom Joon,Han, Moon-Ku,Lee, Jun,Cha, Jae-Kwan,Kim, Dae- Korean Stroke Society 2019 Journal of stroke Vol.21 No.1

<P><B>Background and Purpose</B></P><P>Thrombectomy within 24 hours can improve outcomes in selected patients with a clinical-infarct mismatch. We devised an easy-to-use visual estimation tool that allows infarct volume estimation in centers with limited resources. </P><P><B>Methods</B></P><P>We identified 1,031 patients with cardioembolic or large-artery atherosclerosis infarction on diffusion-weighted images (DWIs) obtained before recanalization therapy and within 24 hours of onset, and occlusion of the internal carotid or middle cerebral artery. Acute DWIs were mapped onto a standard template and used to create visual reference maps with known lesion volumes, which were then used in a validation study (with 130 cases) against software estimates of infarct volume. </P><P><B>Results</B></P><P>The DWI reference map chart comprises 144 maps corresponding to 12 different infarct volumes (0.5, 1, 2, 3, 5, 7, 9, 11, 13, 15, 17, and 19 mL) in each of 12 template slices (Montreal Neurological Institute z-axis –15 to 51 mm). Infarct volume in a patient is estimated by selecting a slice with a similar infarct size at the corresponding z-axis level on the reference maps and then adding up over all slices. The method yielded good correlations to software volumetrics and was easily learned by both experienced and junior physicians, with approximately 1 to 2 minutes spent per case. The sensitivity, specificity, and accuracy for detecting threshold infarct volumes (<21, <31, and <51 mL) were very high (all about >90%). </P><P><B>Conclusions</B></P><P>We developed easy-to-use reference maps that allow prompt and reliable visual estimation of infarct volumes for triaging patients to thrombectomy in acute stroke.</P>

Biomarkers for Stroke

Kim, Suk Jae,Moon, Gyeong Joon,Bang, Oh Young Korean Stroke Society 2013 Journal of stroke Vol.15 No.1

<P><B>Background</B></P><P>Major stroke clinical trials have failed during the past decades. The failures suggest the presence of heterogeneity among stroke patients. Biomarkers refer to indicators found in the blood, other body fluids or tissues that predicts physiologic or disease states, increased disease risk, or pharmacologic responses to a therapeutic intervention. Stroke biomarkers could be used as a guiding tool for more effective personalized therapy.</P><P><B>Main Contents</B></P><P>Three aspects of stroke biomarkers are explored in detail. First, the possible role of biomarkers in patients with stroke is discussed. Second, the limitations of conventional biomarkers (especially protein biomarkers) in the area of stroke research are presented with the reasons. Lastly, various types of biomarkers including traditional and novel genetic, microvesicle, and metabolomics-associated biomarkers are introduced with their advantages and disadvantages. We especially focus on the importance of comprehensive approaches using a variety of stroke biomarkers.</P><P><B>Conclusion</B></P><P>Although biomarkers are not recommended in practice guidelines for use in the diagnosis or treatment of stroke, many efforts have been made to overcome the limitations of biomarkers. The studies reviewed herein suggest that comprehensive analysis of different types of stroke biomarkers will improve the understanding of individual pathophysiologies and further promote the development of screening tools for of high-risk patients, and predicting models of stroke outcome and rational stroke therapy tailored to the characteristics of each case.</P>

Deep into the Brain: Artificial Intelligence in Stroke Imaging

Lee, Eun-Jae,Kim, Yong-Hwan,Kim, Namkug,Kang, Dong-Wha Korean Stroke Society 2017 Journal of stroke Vol.19 No.3

<P>Artificial intelligence (AI), a computer system aiming to mimic human intelligence, is gaining increasing interest and is being incorporated into many fields, including medicine. Stroke medicine is one such area of application of AI, for improving the accuracy of diagnosis and the quality of patient care. For stroke management, adequate analysis of stroke imaging is crucial. Recently, AI techniques have been applied to decipher the data from stroke imaging and have demonstrated some promising results. In the very near future, such AI techniques may play a pivotal role in determining the therapeutic methods and predicting the prognosis for stroke patients in an individualized manner. In this review, we offer a glimpse at the use of AI in stroke imaging, specifically focusing on its technical principles, clinical application, and future perspectives.</P>

Prevention and Management of Cerebral Small Vessel Disease

Mok, Vincent,Kim, Jong S. Korean Stroke Society 2015 Journal of stroke Vol.17 No.2

<P>Lacunar infarcts/lacunes, white matter hyperintensities (WMH), and cerebral microbleeds (CMBs) are considered various manifestations of cerebral small vessel disease (SVD). Since the exact mechanisms of these manifestations differ, their associated risk factors differ. High blood pressure is the most consistent risk factor for all of these manifestations. However, a 'J curve' phenomenon in terms of blood pressure probably exists for WMH. The association between cholesterol levels and lacunar infarcts/lacunes or WMH was less consistent and sometimes conflicting; a low cholesterol level probably increases the risk of CMBs. Homocysteinemia appears to be associated with WMH. It is noteworthy that the risk factors profile may also differ between different lacunar patterns and CMBs located at different parts of the brain. Thrombolysis, antihypertensives, and statins are used to treat patients with symptomatic lacunar infarction, just as in those with other stroke subtypes. However, it should be remembered that bleeding risks increase in patients with extensive WMH and CMBs after thrombolysis therapy. According to the Secondary Prevention of Small Subcortical Strokes trial results, a blood pressure reduction to <130 mmHg is recommended in patients with symptomatic lacunar infarction. However, an excessive blood pressure decrease may induce cognitive decline in older patients with extensive WMH. Dual antiplatelet therapy (aspirin plus clopidogrel) should be avoided because of the excessive risk of intracerebral hemorrhage. Although no particular antiplatelet is recommended, drugs such as cilostazol or triflusal may have advantages for patients with SVD since they are associated with less frequent bleeding complications than aspirin.</P>