Efficacy of Endovascular Thrombectomy in Acute Basilar Artery Occlusion with Low PC-ASPECTS: A Nationwide Prospective Registry-Based Study.

OBJECTIVE: We evaluated the efficacy of endovascular thrombectomy (EVT) on the functional outcome of patients with acute basilar artery occlusion and low posterior circulation acute stroke prognosis early computed tomography score (PC-ASPECTS). METHODS: We identified patients with acute ischemic stroke due to basilar artery occlusion and PC-ASPECTS of 6 or less, presenting within 24 h between August 2008 and April 2022. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-3 at 90 days. The secondary outcomes included an mRS score of 0-2, a favorable shift in the ordinal mRS scale, the occurrence of symptomatic intracranial hemorrhage (sICH), and mortality at 90 days. We compared the outcome of patients treated with EVT and those without EVT, using the inverse probability of treatment weighting methods. RESULTS: Out of 566 patients, 55.5% received EVT. In the EVT group, 106 (33.8%) achieved favorable outcomes, compared to 56 patients (22.2%) in the conservative group. EVT significantly increased the likelihood of achieving a favorable outcome compared to conservative treatment (relative risk [RR] 1.39, 95% confidence interval [CI], 1.11-1.74, p = 0.004). EVT was associated with a favorable shift in the mRS (RR 1.85, 95% CI, 1.49-2.29, p < 0.001) and reduced mortality without an increase in the risk of sICH. It did not have an impact on achieving an mRS score of 0-2. INTERPRETATION: Patients with acute basilar artery occlusion and a PC-ASPECTS of 6 or less might benefit from EVT without an increasing sICH. ANN NEUROL 2024;95:788-799.

Prevalence of Mutations in Mendelian Stroke Genes in Early Onset Stroke Patients.

OBJECTIVE: Heritability of stroke is assumed not to be low, especially in the young stroke population. However, most genetic studies have been performed in highly selected patients with typical clinical or neuroimaging characteristics. We investigated the prevalence of 15 Mendelian stroke genes and explored the relationships between variants and the clinical and neuroimaging characteristics in a large, unselected, young stroke population. METHODS: We enrolled patients aged ≤55 years with stroke or transient ischemic attack from a prospective, nationwide, multicenter stroke registry. We identified clinically relevant genetic variants (CRGVs) in 15 Mendelian stroke genes (GLA, NOTCH3, HTRA1, RNF213, ACVRL1, ENG, CBS, TREX1, ABCC6, COL4A1, FBN1, NF1, COL3A1, MT-TL1, and APP) using a customized, targeted next generation sequencing panel. RESULTS: Among 1,033 patients, 131 (12.7%) had 28 CRGVs, most frequently in RNF213 (n = 59), followed by ABCC6 (n = 53) and NOTCH3 (n = 15). The frequency of CRGVs differed by ischemic stroke subtypes (p < 0.01): the highest in other determined etiology (20.1%), followed by large artery atherosclerosis (13.6%). It also differed between patients aged ≤35 years and those aged 51 to 55 years (17.1% vs 9.3%, p = 0.02). Only 27.1% and 26.7% of patients with RNF213 and NOTCH3 variants had typical neuroimaging features of the corresponding disorders, respectively. Variants of uncertain significance (VUSs) were found in 15.4% patients. INTERPRETATION: CRGVs in 15 Mendelian stroke genes may not be uncommon in the young stroke population. The majority of patients with CRGVs did not have typical features of the corresponding monogenic disorders. Clinical implications of having CRGVs or VUSs should be explored. ANN NEUROL 2023;93:768-782.

Covert Brain Infarction as a Risk Factor for Stroke Recurrence in Patients With Atrial Fibrillation.

BACKGROUND: We aimed to evaluate covert brain infarction (CBI), frequently encountered during the diagnostic work-up of acute ischemic stroke, as a risk factor for stroke recurrence in patients with atrial fibrillation (AF). METHODS: For this prospective cohort study, from patients with acute ischemic stroke hospitalized at 14 centers between 2017 and 2019, we enrolled AF patients without history of stroke or transient ischemic attack and divided them into the CBI (+) and CBI (-) groups. The 2 groups were compared regarding the 1-year cumulative incidence of recurrent ischemic stroke and all-cause mortality using the Fine and Gray subdistribution hazard model with nonstroke death as a competing risk and the Cox frailty model, respectively. Each CBI lesion was also categorized into either embolic-appearing (EA) or non-EA pattern CBI. Adjusted hazard ratios and 95% CIs of any CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were estimated. RESULTS: Among 1383 first-ever stroke patients with AF, 578 patients (41.8%) had CBI. Of these 578 with CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were 61.8% (n=357), 21.8% (n=126), and 16.4% (n=95), respectively. The estimated 1-year cumulative incidence of recurrent ischemic stroke was 5.2% and 1.9% in the CBI (+) and CBI (-) groups, respectively (P=0.001 by Gray test). CBI increased the risk of recurrent ischemic stroke (adjusted hazard ratio [95% CI], 2.91 [1.44-5.88]) but did not the risk of all-cause mortality (1.32 [0.97-1.80]). The EA pattern CBI only and both CBIs elevated the risk of recurrent ischemic stroke (2.76 [1.32-5.77] and 5.39 [2.25-12.91], respectively), while the non-EA pattern only did not (1.44 [0.40-5.16]). CONCLUSIONS: Our study suggests that AF patients with CBI might have increased risk of recurrent stroke. CBI could be considered when estimating the stroke risk in patients with AF.

Improvement in Delivery of Ischemic Stroke Treatments but Stagnation of Clinical Outcomes in Young Adults in South Korea.

BACKGROUND: There is limited information on the delivery of acute stroke therapies and secondary preventive measures and clinical outcomes over time in young adults with acute ischemic stroke. This study investigated whether advances in these treatments improved outcomes in this population. METHODS: Using a prospective multicenter stroke registry in Korea, young adults (aged 18-50 years) with acute ischemic stroke hospitalized between 2008 and 2019 were identified. The observation period was divided into 4 epochs: 2008 to 2010, 2011 to 2013, 2014 to 2016, and 2017 to 2019. Secular trends for patient characteristics, treatments, and outcomes were analyzed. RESULTS: A total of 7050 eligible patients (mean age, 43.1; men, 71.9%) were registered. The mean age decreased from 43.6 to 42.9 years (Ptrend=0.01). Current smoking decreased, whereas obesity increased. Other risk factors remained unchanged. Intravenous thrombolysis and mechanical thrombectomy rates increased over time from 2008 to 2010 to 2017 to 2019 (9.5%-13.8% and 3.2%-9.2%, respectively; Ptrend<0.01). Door-to-needle time improved (Ptrend <.001), but onset-to-door and door-to-puncture times remained constant. Secondary prevention, including dual antiplatelets for noncardioembolic minor stroke (26.7%-47.0%), direct oral anticoagulants for atrial fibrillation (0.0%-56.2%), and statins for large artery atherosclerosis (76.1%-95.3%) increased (Ptrend<0.01). Outcome data were available from 2011. One-year mortality (2.5% in 2011-2013 and 2.3% in 2017-2019) and 3-month modified Rankin Scale scores 0 to 1 (68.3%-69.1%) and 0 to 2 (87.6%-86.2%) remained unchanged. The 1-year stroke recurrence rate increased (4.1%-5.5%; Ptrend=0.04), although the difference was not significant after adjusting for sex and age. CONCLUSIONS: Improvements in the delivery of acute stroke treatments did not necessarily lead to better outcomes in young adults with acute ischemic stroke over the past decade, indicating a need for further progress.

Mortality of Deep Brain Stimulation and Risk Factors in Patients With Parkinson's Disease: A National Cohort Study in Korea.

BACKGROUND: This study aimed to investigate 1) long-term outcomes of deep brain stimulation (DBS), such as mortality after DBS as well as the causes of death, 2) demographic and socioeconomic factors influencing mortality, and 3) comorbidities affecting mortality after DBS in patients with Parkinson's disease (PD). METHODS: This study analyzed the National Health Insurance Service-National Health Information Database. Data on patients with PD diagnosis codes from 2002 to 2019 were extracted and analyzed. Data on the causes of death were obtained by linking the causes of death to data from Statistics Korea. The Kaplan-Meier method with the log-rank test was used for survival analysis. Multivariate Cox regression analyses were used to estimate hazard ratios (HRs) and their 95% confidence intervals. Regarding comorbidities such as PD dementia and fracture, which did not satisfy the assumption for the proportional HR, time-dependent Cox analysis with the Mantel-Byar method was used. RESULTS: From 2005 to 2017, among 156,875 patients diagnosed with PD in Korea, 1,079 patients underwent DBS surgery, and 251 (23.3%) had died by 2019. The most common cause of death (47.1%) was PD. In the multivariate Cox regression analysis, the higher the age at diagnosis and surgery, the higher the mortality rate. The men and medical aid groups had significantly higher mortality rates. PD dementia and fracture were identified as risk factors for mortality. CONCLUSION: Older age at diagnosis and surgery, being male, the use of medical aid, and the comorbidity of dementia and fractures were associated with a higher risk of mortality after DBS in patients with PD. Neurologists should consider these risk factors in assessing the prognosis of PD patients undergoing DBS.

Frequency, management, and outcomes of early neurologic deterioration due to stroke progression or recurrence.

OBJECTIVE: The frequency, management, and outcomes of early neurologic deterioration (END) after ischemic stroke specifically due to stroke progression or stroke recurrence have not been well delineated. MATERIALS AND METHODS: In a multicenter, nationwide registry, data on END due to stroke progression or recurrence confirmed by imaging were collected prospectively between January 2019 and July 2020. Patient characteristics, management strategies, and clinical outcomes were analyzed. RESULTS: Among 14,828 consecutive ischemic stroke patients, 1717 (11.6%) experienced END, including 1221 (8.2%) with END due to stroke progression (SP) or stroke recurrence (SR). Active management after END was implemented in 64.2% of patients. Active management strategies included volume expansion (29.2%), change in antithrombotic regimen (26.1%), induced hypertension (8.6%), rescue reperfusion therapy (6.8%), intracranial pressure lowering with hyperosmolar agents (1.5%), bypass surgery (0.6%), and hypothermia (0.1%). Active management strategies that varied with patient features included volume expansion and induced hypertension, used more often in large artery atherosclerosis and small vessel occlusion, and rescue endovascular thrombectomy, more common in other (dissection), cardioembolism, and large artery atherosclerosis. Active management was associated with higher rates of freedom from disability (modified Rankin Scale, mRS, 0-1; 24.3% vs. 16.6%) and functional independence (mRS, 0-2; 41.6% vs. 27.7%) at 3 months. CONCLUSION: END specifically due to stroke progression or recurrence occurs in 1 in 12 acute ischemic stroke patients. In this observational study, active management, undertaken in two-thirds of patients, was most often hemodynamic or antithrombotic and was associated with improved functional outcomes.

Stroke of Other Determined Etiology: Results From the Nationwide Multicenter Stroke Registry.

BACKGROUND: Stroke of other determined etiology (OE) includes patients with an uncommon cause of stroke. We described the general characteristics, management, and outcomes of stroke in OE and its subgroups. METHODS: This study is a retrospective analysis of a prospective, multicenter, nationwide registry, the Clinical Research Center for Stroke-Korea-National Institutes of Health registry. We classified OE strokes into 10 subgroups according to the literature and their properties. Each OE subgroup was compared according to clinical characteristics, sex, age strata, lesion locations, and management. Moreover, 1-year composites of stroke and all-cause mortality were investigated according to the OE subgroups. RESULTS: In total, 2119 patients with ischemic stroke with OE types (mean age, 55.6±16.2 years; male, 58%) were analyzed. In the Clinical Research Center for Stroke-Korea-National Institutes of Health registry, patients with OE accounted for 2.8% of all patients with stroke. The most common subtypes were arterial dissection (39.1%), cancer-related coagulopathy (17.3%), and intrinsic diseases of the arterial wall (16.7%). Overall, strokes of OE were more common in men than in women (58% versus 42%). Arterial dissection, intrinsic diseases of the arterial wall and stroke associated with migraine and drugs were more likely to occur at a young age, while disorders of platelets and the hemostatic system, cancer-related coagulopathy, infectious diseases, and hypoperfusion syndromes were more frequent at an old age. The composite of stroke and all-cause mortality within 1 year most frequently occurred in cancer-related coagulopathy, with an event rate of 71.8%, but least frequently occurred in stroke associated with migraine and drugs and arterial dissection, with event rates of 0% and 7.2%, respectively. CONCLUSIONS: This study presents the different characteristics, demographic findings, lesion locations, and outcomes of OE and its subtypes. It is characterized by a high proportion of arterial dissection, high mortality risk in cancer-related coagulopathy and an increasing annual frequency of cancer-related coagulopathy in patients with stroke of OE.

Underweight predicts poststroke cardiovascular events in patients without atrial fibrillation.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether underweight is associated with poststroke cardiovascular events and whether such association is different according to the presence of atrial fibrillation (AF). METHODS: Patients with acute stroke or transient ischemic attack who were prospectively registered in a multicenter stroke database from April 2008 to July 2020 were analyzed, excluding those aged 75 or older and those who were overweight. We prospectively captured major adverse cardiovascular events (MACE) within one year after stroke. Cox-proportional hazard regression analysis was conducted for each subgroup with or without AF after adjusting for predetermined vascular risk factors and potential confounders. RESULTS: Among 30,912 patients, 1494 (4.8%) cases were underweight and 29,418 (95.2%) cases were normal weight. The cumulative event rate of 1-year MACE was higher in the underweight group (9.0%) than in the normal weight group (5.6%). In Cox-proportional regression, underweight was associated with significantly higher MACE (adjusted hazard ratio [HR]: 1.62, 95% confidence interval [CI]: 1.26-2.09) and recurrent stroke (adjusted HR: 1.42, 95% CI: 1.02-1.98) in all study patients. In patients with AF, the risk of MACE for the underweight group was not significantly increased. In contrast, in patients without AF, the underweight group had a consistently higher risk of MACE (adjusted HR: 1.66, 95% CI: 1.25-2.22) and recurrent stroke (adjusted HR: 1.50, 95% CI: 1.05-2.14). CONCLUSIONS: Underweight increased the risk of MACE and recurrent stroke within one year after acute stroke, especially in stroke without AF.

Cilostazol Versus Aspirin in Ischemic Stroke Patients With High-Risk Cerebral Hemorrhage: Subgroup Analysis of the PICASSO Trial.

Background and Purpose- Although cilostazol has shown less hemorrhagic events than aspirin, only marginal difference was observed in hemorrhagic stroke events among patients at high risk for cerebral hemorrhage. To identify patients who would most benefit from cilostazol, this study analyzed interactions between treatment and subgroups of the PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage). Methods- Ischemic stroke patients with a previous intracerebral hemorrhage or multiple microbleeds were randomized to treatment with cilostazol or aspirin and followed up for a mean 1.8 years. Efficacy, defined as the composite of any stroke, myocardial infarction, and vascular death, and safety, defined as the incidence of hemorrhagic stroke, were analyzed in the 2 groups. Interactions between treatment and age, sex, presence of hypertension and diabetes mellitus, index of high-risk cerebral hemorrhage, and white matter lesion burden were analyzed for primary and key secondary outcomes. Changes in vital signs and laboratory results were compared in the 2 groups. Results- Among all 1534 patients enrolled, a significant interaction between treatment group and index of high risk for cerebral hemorrhage on hemorrhagic stroke (P for interaction, 0.03) was observed. Hemorrhagic stroke was less frequent in the cilostazol than in the aspirin group in patients with multiple microbleeds (1 versus 13 events; hazard ratio, 0.08 [95% CI, 0.01-0.61]; P=0.01). A marginal interaction between treatment group and white matter change on any stroke (P for interaction, 0.08) was observed. Cilostazol reduced any stroke significantly in patients with mild (5 versus 16 events; hazard ratio, 0.36 [95% CI, 0.13-0.97]; P=0.04)-to-moderate (16 versus 32 events; hazard ratio, 0.50 [95% CI, 0.29-0.92]; P=0.03) white matter changes. Heart rate and HDL (high-density lipoprotein) cholesterol level were significantly higher in the cilostazol group than in the aspirin group at follow-up. Conclusions- Cilostazol may be more beneficial for ischemic stroke patients with multiple cerebral microbleeds and before white matter changes are extensive. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01013532.

Effect of Heart Rate on Stroke Recurrence and Mortality in Acute Ischemic Stroke With Atrial Fibrillation.

Background and Purpose- There is a paucity of information about the role of resting heart rate in the prediction of outcome events in patients with ischemic stroke with atrial fibrillation. We aimed to investigate the relationships between the level and variability of heart rate in the acute stroke period and stroke recurrence and mortality after acute ischemic stroke in patients with atrial fibrillation. Methods- Acute patients with ischemic stroke who had atrial fibrillation and were hospitalized within 48 hours of stroke onset were identified from a multicenter prospective stroke registry database. The acute stroke period was divided into early (within 24 hours of hospitalization) and late (72 hours to 7 days from onset) stages, and data on heart rate in both stages were collected. Moreover, the level and variability of heart rate were assessed using mean values and coefficients of variation. Outcome events were prospectively monitored up to 1 year after the index stroke. Results- Among 2046 patients eligible for the early acute stage analysis, 102 (5.0%) had a stroke recurrence, and 440 (21.5%) died during the first year after stroke. A statistically significant nonlinear J-shaped association was observed between mean heart rate and mortality (P<0.04 for quadratic and overall effect) but not between mean heart rate and stroke recurrence (P>0.1 for quadratic and overall effect). The nonlinear and overall effects of the coefficients of variation of heart rate were not significant for all outcome variables. The same results were observed in the late acute stage analysis (n=1576). Conclusions- In patients with atrial fibrillation hospitalized for acute ischemic stroke, the mean heart rate during the acute stroke period was not associated with stroke recurrence but was associated with mortality (nonlinear, J-shaped association). The relationships between heart rate and outcomes were not observed with respect to heart rate variability.

Comparative Effectiveness of Dual Antiplatelet Therapy With Aspirin and Clopidogrel Versus Aspirin Monotherapy in Acute, Nonminor Stroke: A Nationwide, Multicenter Registry-Based Study.

Background and Purpose- This study aimed to compare the effectiveness of dual antiplatelet therapy with clopidogrel plus aspirin (DAPT) with that of aspirin monotherapy (AM) in patients with acute, nonminor, and noncardioembolic stroke. Methods- Using a prospective, nationwide, multicenter stroke registry database, acute (within 24 hours of onset), nonminor (baseline National Institutes of Health Stroke Scale score, 4-15), and noncardioembolic stroke patients were identified. Propensity scores using inverse probability of treatment weighting were used to adjust baseline imbalances between the DAPT and AM groups. A primary outcome measure was a composite of all types of stroke (ischemic and hemorrhagic), myocardial infarction, and all-cause mortality within 3 months of stroke onset. Results- Among the 4461 patients meeting the eligibility criteria (age, 69±13 years; men, 57.7%), 52.5% (n=2340) received AM, and 47.5% (n=2121) received DAPT. The primary outcome event was not significantly different between the DAPT group and the AM group (20.9% versus 22.6%, P=0.13). The event rates of all types of stroke were also not different between the 2 groups (19.3% versus 20.1%, P=0.35), while all-cause mortality was significantly lower in the DAPT group than in the AM group (3.4% versus 4.9%, P=0.02). In the propensity-weighted Cox proportional hazards models with robust estimation, DAPT did not reduce the risk of the primary outcome event (hazards ratio, 0.91; 95% CI, 0.79-1.04) but did reduce the risk of all-cause mortality (0.69; 0.49-0.97). There was no treatment heterogeneity among the predefined subgroups, although the potential benefits of DAPT were suggested in subpopulations of moderate-to-severe relevant arterial stenosis and relatively severe deficits (National Institutes of Health Stroke Scale score, 12-15). Conclusions- Compared to AM, clopidogrel plus aspirin did not reduce the risk of the primary outcome event during the first 3 months after a nonminor, noncardioembolic, ischemic stroke.

Dual Versus Mono Antiplatelet Therapy in Large Atherosclerotic Stroke.

Background and Purpose- Two large-scale randomized controlled trials of recurrent stroke prevention suggest that dual antiplatelet therapy with clopidogrel plus aspirin is beneficial for prevention of subsequent ischemic events. There is a paucity of data, however, on the efficacy or effectiveness of such an approach in the treatment of stroke patients with symptomatic large artery atherosclerotic occlusive disease. Methods- We used a multicenter stroke registry database (Clinical Research Collaboration for Stroke in Korea) to analyze acute ischemic stroke patients due to large artery atherosclerotic occlusive disease who were treated with aspirin alone or combination of clopidogrel and aspirin from May 2008 to May 2015. The results were analyzed by intention-to-treat, per-protocol, and as-treated methodologies. The primary end point was the 1-year composite outcome of stroke recurrence, myocardial infarction, and all-cause death. To balance the differences between groups, a frailty model using propensity scores and inverse probability of treatment weighting was used. Results- A total of 5934 patients with symptomatic large artery atherosclerotic occlusive disease were treated either with clopidogrel plus aspirin (n=2903, 49%) or aspirin (n=3031, 51%). The frequency of the primary outcome was 12% (n=353) in the clopidogrel-aspirin group and 14% (n=410) in the aspirin group. The hazards of the primary outcome with combination over aspirin only were significantly reduced in the per-protocol and as-treated analyses (hazard ratio, 0.71; 95% CI, 0.57-0.88; P=0.002 and hazard ratio, 0.81; 95% CI, 0.69-0.96; P=0.02, respectively), but there was borderline significance in the intention-to-treat analysis (hazard ratio, 0.86; 95% CI, 0.74-1.01; P=0.06). Combination therapy was beneficial for all-cause death in all analyses but did not reduce recurrent stroke. Conclusions- Compared with patients receiving aspirin monotherapy, the primary outcome seemed to occur less frequently in patients receiving dual antiplatelet therapy, which is explained mainly by the decrease of all-cause death. Since this is a nonrandomized, retrospective, observational study, our study should be cautiously interpreted.

Magnetic Resonance Imaging Versus Computed Tomography Angiography Based Selection for Endovascular Therapy in Patients With Acute Ischemic Stroke.

Background and Purpose- Randomized trials comparing the use of multimodal magnetic resonance imaging (MRI) to multimodal computed tomography (CT)/ CT angiography (CTA) for selecting candidates for endovascular therapy (EVT) have not been reported. This study aimed to elucidate whether MRI-based selection for EVT is safe and effective within and after a 6-hour time window compared with conventional CTA-based selection. Methods- Data from a prospective, nationwide, multicenter stroke registry were analyzed. Workflow timelines were compared between patients selected for EVT based on MRI (the MRI group) and CTA (the CTA group). Multivariable ordinal and binary logistic regression analyses were performed to explore the relationships between decision imaging for EVT and clinical outcomes, including good and excellent outcomes (modified Rankin Scale scores of 0-2 and 0-1, respectively) at 3-month, modified Rankin Scale score distributions and safety outcomes (symptomatic intracranial hemorrhage [SICH] and mortality). Results- Ultimately, 1265 patients (age, 69±12 yrs; men, 55%) were enrolled in this study. The median National Institutes of Health Stroke Scale score was 15 (11-19). All workflow time metrics were significantly delayed in the MRI group compared with the CTA group. There was no difference in good 3-month outcomes in patients arriving within 6 hours of onset between the MRI and CTA groups (38.1% versus 38.5%), but SICH and mortality rates were lower in the MRI group than the CTA group (3.8% versus 7.7%, P=0.01 for SICH; 15.4% versus 20.9%, P=0.04 for mortality). In the multivariable analysis, decision imaging was not significantly associated with 3-month functional outcomes (all P>0.1) or mortality ( P=0.051); however, the MRI group was less likely to develop SICH than the CTA group ( P=0.01; odds ratio, 0.34 [95% CI, 0.17-0.77]). Conclusions- Our study found MRI-based selection for EVT was not associated with improving functional outcome compared with CT-based selection, but may be better at reducing the risk of SICH, despite the delays in all workflow time metrics.

Comparative Effectiveness of Aspirin and Clopidogrel Versus Aspirin in Acute Minor Stroke or Transient Ischemic Attack.

Background and Purpose- This study aimed to compare the effectiveness of dual antiplatelet therapy with clopidogrel-aspirin to that of aspirin monotherapy in patients with acute minor cerebral ischemia using a prospective, nationwide, multicenter, stroke registry database in South Korea. Methods- CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events)-like patients who met eligibility criteria modeled on the CHANCE trial eligibility criteria, including (1) acute minor ischemic stroke defined as National Institutes of Health Stroke Scale score ≤3 or lesion positive transient ischemic attack within 24 hours of onset and (2) noncardioembolic stroke mechanism. Propensity scores using the inverse probability of treatment weighting was used to adjust for baseline imbalances. The primary outcome was the composite of all stroke (ischemic and hemorrhagic), myocardial infarction, and vascular death by 3 months. Results- Among 5590 patients meeting the eligibility criteria, age was 64±13 year and 62.6% were male. Aspirin and combination of clopidogrel-aspirin were administered in 66.1% and 33.9% of patients, respectively. In unadjusted analysis, rates of the 3-month primary vascular event outcome were lower with clopidogrel-aspirin versus aspirin, 9.9% versus 12.2% (hazard ratio, 0.79 [0.67-0.95]). In propensity-weighted Cox proportional hazards regression with robust estimation, clopidogrel-aspirin was associated with a lower risk of the primary vascular event outcome (hazard ratio, 0.76 [0.63-0.92]) and all stroke events (hazard ratio, 0.74 [0.61-0.90]). Among 6 predefined subgroup analyses, 3 showed potential modification of treatment effect, with lesser benefit associated with the absence of prior antiplatelet use (Pinteraction=0.01) and younger age (<75 years, Pinteraction=0.07), and absence of benefit associated with small vessel occlusion subtype (Pinteraction=0.08). Conclusions- Dual antiplatelet therapy with aspirin and clopidogrel was associated with reduced stroke, myocardial infarction, and vascular death in the 3 months following a presenting minor, noncardioembolic ischemic stroke. Benefits may be particularly magnified in patients with a history of prior antiplatelet therapy, older age, and nonsmall vessel disease stroke mechanism.

Factors contributing to excessive daytime sleepiness in Korean adults with epilepsy: A sleep questionnaire-based study.

OBJECTIVES: We determined factors contributing to excessive daytime sleepiness (EDS) in Korean adults with epilepsy (AWE). METHODS: A total of 147 AWE who had been treated for >1 year were included. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). Subjective sleep disturbances were assessed with the Sleep Apnea of Sleep Disorder Questionnaire (SA-SDQ) and questionnaires about insomnia and restless legs syndrome (RLS). The Hospital Anxiety and Depression Scale (HADS) was also used. An ESS score >10 was considered indicative of EDS. Multivariate logistic regression analyses using the backward elimination method were performed for variables with a p < 0.10 on univariate analysis. RESULTS: The mean ESS score was 6.8 (standard deviation [SD]: 4.4). Among the 147 subjects, 36 (24.5%) had EDS. Multivariate logistic regression analysis showed that being employed (odds ratio [OR]: 4.469, p < 0.01), the presence of at least one sleep disturbance (OR: 3.626, p < 0.01), and antiepileptic drug (AED) polytherapy (OR: 2.663, p < 0.05) were independently associated with EDS in the overall group of AWE. In contrast, being employed (p < 0.05) and higher Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A) scores (p < 0.05) in a model for men with epilepsy, as well as having at least one sleep disturbance (p < 0.05) in a model for women with epilepsy, were identified as independent factors for EDS. CONCLUSIONS: Excessive daytime sleepiness in AWE may have a multifactorial origin. Being employed, subjective sleep disturbances, and AED polytherapy are independent predictors of EDS. There may be sex differences in factors associated with EDS.

Predictive Value of Pulse Pressure in Acute Ischemic Stroke for Future Major Vascular Events.

BACKGROUND AND PURPOSE: This study aimed to investigate whether pulse pressure (PP) obtained during the acute stage of ischemic stroke can be used as a predictor for future major vascular events. METHODS: Using a multicenter prospective stroke registry database, patients who were hospitalized for ischemic stroke within 48 hours of onset were enrolled in this study. We analyzed blood pressure (BP) data measured during the first 3 days from onset. Primary and secondary outcomes were time to a composite of stroke recurrence, myocardial infarction, all-cause death, and time to stroke recurrence, respectively. RESULTS: Of 9840 patients, 4.3% experienced stroke recurrence, 0.2% myocardial infarction, and 7.3% death during a 1-year follow-up period. In Cox proportional hazards models including both linear and quadratic terms of PP, PP had a nonlinear J-shaped relationship with primary (for a quadratic term of PP, P=0.004) and secondary (P<0.001) outcomes. The overall effects of PP and other BP parameters on primary and secondary outcomes were also significant (P<0.05). When predictive power of BP parameters was compared using a statistic of -2 log-likelihood differences, PP was a stronger predictor than systolic BP (8.49 versus 5.91; 6.32 versus 4.56), diastolic BP (11.42 versus 11.05; 10.07 versus 4.56), and mean atrial pressure (8.75 versus 5.91; 7.03 versus 4.56) for the primary and secondary outcomes, respectively. CONCLUSIONS: Our study shows that PP when measured in the acute period of ischemic stroke has nonlinear J-shaped relationships with major vascular events and stroke recurrence, and may have a stronger predictive power than other commonly used BP parameters.

Factors contributing to anxiety and depressive symptoms in adults with new-onset epilepsy.

PURPOSE: We investigated factors contributing to anxiety and depressive symptoms over a 1-year period in Korean adults with new-onset epilepsy. METHODS: This longitudinal multicenter study included adults diagnosed with epilepsy within 12 months of a first seizure. Using stepwise regression analyses, we determined whether Hospital Anxiety Depression Scale (HADS) scores could be predicted by demographic, clinical, and psychosocial variables at baseline and at 12 months. RESULTS: Of 141 patients included at baseline, 63 (44.7%) and 60 (42.6%) had Hospital Anxiety Depression Scale-Anxiety (HADS-A) and Hospital Anxiety Depression Scale-Depression (HADS-D) scores >7, respectively. Of 98 patients who completed the 12-month study, the corresponding figures decreased to 32.7% and 36.7%, respectively. Higher HADS-A scores both at baseline and 12 months were predicted by higher neuroticism, stigma, and lower self-esteem (p < 0.05). Higher HADS-D scores at baseline were predicted by higher neuroticism, lower self-esteem, marital status, and lower extroversion (p < 0.05) whereas those at 12 months were predicted by self-esteem, seizure recurrence, and age at epilepsy onset (p < 0.05). Neuroticism or self-esteem was the strongest predictor of psychological distress. CONCLUSIONS: Anxiety and depressive symptoms are common at the time of diagnosis in Korean adults with new-onset epilepsy. While these decrease over time, they remained high 12 months after epilepsy diagnosis. Psychological factors, particularly neuroticism and self-esteem, may be the most important risk factors. Epilepsy variables, such as seizure recurrence and age at onset, may also be important factors for depressed mood at 12 months.

Acute copper sulfate poisoning resulting from dermal absorption.

We report a Korean worker who experienced dermal exposure to a hot copper sulfate solution at his workplace and developed severe acute copper sulfate poisoning. A 53-year-old male worker, who was employed in a lead smelter for 5 years, slipped, and his right lower leg entered a copper sulfate solution, leading to severe burns of the right lower leg. Two days later, he developed severe intravascular hemolysis with methemoglobinemia. He also suffered from acute kidney injury, had an asymptomatic cerebral ischemic stroke, and melena due to multiple shallow gastric ulcers. His serum copper level was mildly elevated (153.6 µg/dL, reference: 64.0-134 µg/dL). He was transfused with red blood cell concentrate and supported by hemodialysis. After 13 sessions of hemodialysis and several blood transfusions, he completely recovered. Most previously reported incidents of severe acute copper sulfate poisoning were from accidental or suicidal oral intake. There are few previous reports of systemic copper sulfate toxicity following exposure through burned skin.

Predictors of disclosure management behavior at the end of 1-year follow-up in Korean adults with newly diagnosed epilepsy.

PURPOSE: Epilepsy is a concealable stigmatizing condition. We investigated the factors predicting disclosure management behavior in Korean adults with newly diagnosed epilepsy. METHODS: This longitudinal multicenter study included Korean adults with newly diagnosed epilepsy. Using statistical analyses, we determined at the end of a 1-year follow-up whether Disclosure Management Scale (DMS) scores were predicted by demographic, clinical, and psychosocial variables, including felt stigma, stress coping style, personality traits, social support, and experienced discrimination from society. RESULTS: Of a total of 121 participants, 69% reported that they often or sometimes kept their diagnosis a secret from others and rarely or never talked to others about their epilepsy. The average DMS score was 5.8 (SD=2.9, range 0-11). In univariate analyses, DMS scores were significantly associated with an emotion-focused coping style (r=0.320, p<0.001), social support (r=-0.185, p<0.05), and experienced discrimination (p<0.05). Emotion-focused coping was the only independent predictor of a higher DMS score. Felt stigma, personality traits, and seizure freedom were not related to the DMS score. CONCLUSIONS: Two-thirds of Korean adults with newly diagnosed epilepsy often or sometimes keep their epilepsy a secret. Emotion-focused coping is the most important predictor of concealment of epilepsy diagnosis at the end of a 1-year follow-up, although social support and episodes of experienced discrimination are also associated with disclosure management strategies.

Factors contributing to the development of perceived stigma in people with newly diagnosed epilepsy: A one-year longitudinal study.

PURPOSE: We evaluated the course of perceived stigma and the factors associated with perceived stigma over the first year in newly diagnosed people with epilepsy (PWE). METHODS: We recruited newly diagnosed PWE from 12 tertiary hospitals in Korea. The perceived stigma of epilepsy was assessed using the Stigma Scale at baseline and one year later. At the time of diagnosis, demographic, clinical seizure-related, and psychological data were collected. The predictive factors for perceived stigma over one year were analyzed using logistic regression analyses. RESULTS: Two hundred eighteen newly diagnosed PWE were included at baseline, and 153 completed the study. The percentage of participants who felt stigmatized decreased from 30.7% at the time of diagnosis to 17.6% at the end of follow-up. Introverted personality and a high level of anxiety were independent factors contributing to stigma at the time of epilepsy diagnosis. At the one-year follow-up, introverted personality and lower economic status were predictive of the development of perceived stigma. CONCLUSION: Introverted personality was an important factor contributing to the development of perceived stigma at the time of diagnosis and at one year after diagnosis. In addition, a high level of anxiety and a low economic status were independently related to feelings of stigma at baseline and at one year after diagnosis, respectively. There may be a decrease in the perception of stigma over one year in newly diagnosed PWE.