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.

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.

Quantitative radiological analysis and clinical outcomes of urgent EC-IC bypass for hemodynamic compromised patients with acute ischemic stroke.

This study aimed to demonstrate the effectiveness of urgent extracranial-to-intracranial bypass (EIB) in acute ischemic stroke (AIS) through quantitative analysis of computed tomography perfusion (CTP) results using RAPID software. We retrospectively analyzed 41 patients who underwent urgent EIB for AIS under strict operation criteria. The quantitative data from CTP images were reconstructed to analyze changes in pre- and postoperative perfusion status in terms of objective numerical values using RAPID software. Short- and long-term clinical outcomes, including complications and neurological status, were also analyzed. Postoperatively, the volume of time-to-max (Tmax) > 6 s decreased significantly; it continued to improve significantly until 6 months postoperatively (preoperative, 78 ml (median); immediate postoperative, 23 ml; postoperative 6 months, 7 ml; p = 0.000). Ischemic core-penumbra mismatch volumes were also significantly improved until 6 months postoperatively (preoperative, 72 ml (median); immediate postoperative, 23 ml; postoperative 6 months, 5 ml; p = 0.000). In addition, the patients' neurological condition improved significantly (p < 0.001). Only one patient (2.3%) showed progression of infarction. Urgent EIB using strict indications can be a feasible treatment for IAT-ineligible patients with AIS due to large vessel occlusion or stenosis.

Association of ischemic stroke onset time with presenting severity, acute progression, and long-term outcome: A cohort study.

BACKGROUND: Preclinical data suggest circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with inactive phase (daytime) than active phase (nighttime) stroke onset. We aimed to examine the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke. METHODS AND FINDINGS: In a Korean nationwide multicenter observational cohort study from May 2011 to July 2020, we assessed circadian effects on initial stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at admission), END, and favorable functional outcome (3-month modified Rankin Scale [mRS] score 0 to 2 versus 3 to 6). We included 17,461 consecutive patients with witnessed ischemic stroke within 6 hours of onset. Stroke onset time was divided into 2 groups (day-onset [06:00 to 18:00] versus night-onset [18:00 to 06:00]) and into 6 groups by 4-hour intervals. We used mixed-effects ordered or logistic regression models while accounting for clustering by hospitals. Mean age was 66.9 (SD 13.4) years, and 6,900 (39.5%) were women. END occurred in 2,219 (12.7%) patients. After adjusting for covariates including age, sex, previous stroke, prestroke mRS score, admission NIHSS score, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, prestroke antiplatelet use, prestroke statin use, revascularization, season of stroke onset, and time from onset to hospital arrival, night-onset stroke was more prone to END (adjusted incidence 14.4% versus 12.8%, p = 0.006) and had a lower likelihood of favorable outcome (adjusted odds ratio, 0.88 [95% CI, 0.79 to 0.98]; p = 0.03) compared with day-onset stroke. When stroke onset times were grouped by 4-hour intervals, a monotonic gradient in presenting NIHSS score was noted, rising from a nadir in 06:00 to 10:00 to a peak in 02:00 to 06:00. The 18:00 to 22:00 and 22:00 to 02:00 onset stroke patients were more likely to experience END than the 06:00 to 10:00 onset stroke patients. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, falling from a peak at 06:00 to 10:00 to a nadir at 22:00 to 02:00. Study limitations include the lack of information on sleep disorders and patient work/activity schedules. CONCLUSIONS: Night-onset strokes, compared with day-onset strokes, are associated with higher presenting neurologic severity, more frequent END, and worse 3-month functional outcome. These findings suggest that circadian time of onset is an important additional variable for inclusion in epidemiologic natural history studies and in treatment trials of neuroprotective and reperfusion agents for acute ischemic stroke.

Size-Related Differences in Computed Tomography Markers of Hematoma Expansion in Acute Intracerebral Hemorrhage.

BACKGROUND: Noncontrast computed tomography (NCCT) markers for hematoma expansion (HE) in intracerebral hemorrhage (ICH) are difficult to be found in small ICHs, of which can also expand. We aimed to investigate whether there were size-related differences in the prevalence of NCCT markers and their association with HE. METHODS: This retrospective analysis of prospectively collected stroke registry included 267 consecutive patients with ICH who underwent baseline NCCT within 12 h of onset. Qualitative NCCT markers, including heterogeneous density and irregular shape, were assessed. Hematoma density, defined as mean Hounsfield unit of hematoma, and hematoma volume were measured by semiautomated planimetry. Hematoma volume was categorized as small (≤ 10 ml) and large (> 10 ml). Associations of NCCT markers with HE were analyzed using multivariable logistic regression analyses. The model performances of NCCT markers and hematoma density were compared using receiver operating characteristic curves. RESULTS: Hematoma expansion occurred in 29.9% of small ICHs and 35.5% of large ICHs. Qualitative NCCT markers were less frequently observed in small ICHs. Heterogeneous density, irregular shape, and hematoma density were associated with HE in small ICH (adjusted odds ratios [95% confidence interval] 3.94 [1.50-10.81], 4.23 [1.73-10.81], and 0.72 [0.60-0.84], respectively), and hematoma density was also related to HE in large ICH (0.84 [0.73-0.97). The model performance was significantly improved in small ICHs when hematoma density was added to the baseline model (DeLong's test, p = 0.02). CONCLUSIONS: The prevalence of NCCT markers and their association with HE differed according to hematoma volume. Quantitative hematoma density was associated with HE, regardless of hematoma size.

Mediation effects of mean Hounsfield unit on relationship between hemoglobin and expansion of intracerebral hemorrhage.

Low hemoglobin levels are known to be associated with hematoma expansion (HE) and poor functional outcome in patients with intracerebral hemorrhage (ICH). However, it is not yet known whether low hemoglobin itself causes HE directly or is merely a confounder. Thus, we investigated the mediation effect of the mean Hounsfield unit (HU) of hematoma on the relationship between low hemoglobin and expansion of ICH. Overall, 232 consecutive patients with ICH who underwent non-contrast computed tomography (NCCT) within 12 h since onset were included. The mean HU and hematoma volume on NCCT were investigated using semi-automated planimetry. HE was defined as an increase in hematoma volume > 33% or 6 mL. The respective associations among the hemoglobin level, mean HU, and HE were analyzed using multivariable regression analysis, adjusting for age, sex, and known HE predictors. Mediation analysis was performed to examine the potential causal association among the three. HE occurred in 34.5% of patients; hemoglobin levels were inversely associated with HE occurrence (adjusted odds ratio, 0.90; p = 0.03). The mean HU of the hematoma was lower in patients with HE than in patients without HE (58.5 ± 3.3 vs. 56.8 ± 3.0; p < 0.01). Hemoglobin levels on admission were linearly related to the mean HU (adjusted ß, 0.33; p < 0.01) after adjusting for known HE predictors (time from onset to CT, antithrombotic use, hematoma volume). Causal mediation analysis showed a significant mediation effect of the mean HU on the association between hemoglobin levels and HE (p = 0.04). The proportion of indirect effect through the mean HU among the total effect was 19% (p = 0.05). The mediation effect became nonsignificant in the when the multivariable model was adjusted with additional covariates (baseline systolic blood pressure and hematoma location). The mean HU of the hematoma mediated the association between hemoglobin levels and HE occurrence. Therefore, the mean HU of the hematoma may be a potential marker of impaired hemostasis in patients with ICH.

Blood Pressure and Transient Postoperative Neurologic Deterioration, Following Superficial Temporal-to-Middle Cerebral Artery Anastomosis in Adult Patients with Moyamoya Disease: A Retrospective Cohort Study.

We investigated whether intraoperative systolic blood pressure (ISBP) is associated with the risk of transient neurologic deficits (TND) following superficial temporal-to-middle cerebral artery (STA-MCA) anastomosis in adult patients with moyamoya disease (MMD). In this retrospective observational study, data from adult patients with MMD who had undergone STA-MCA anastomosis at a single tertiary academic hospital during May 2003-April 2014 were examined. Data on patient characteristics were obtained from electronic medical records, including the details of comorbidities and laboratory findings. TND was the primary outcome of interest. Out of 192 patients (228 hemispheres), 66 (29%) hemispheres had TND after surgery. There were significant differences in ISBP between patients with and without TND. The lowest ISBP quartile was independently associated with TND (odds ratio: 5.50; 95% confidence interval: 1.96-15.46). Low ISBP might lead to TND after STA-MCA anastomosis in adult patients with MMD. In patients with poor perfusion status, low ISBP was associated with an increased risk of TND. Our findings suggest that strict ISBP control might be required to prevent TND after anastomosis in patients with MMD, in particular, in patients with poor perfusion status. Given limitations due to the retrospective design, further studies are needed to clarify these findings.

Intravenous Fluid Selection for Unruptured Intracranial Aneurysm Clipping : Balanced Crystalloid versus Normal Saline.

OBJECTIVE: While balanced crystalloid (BC) could be a relevant fluid regimen with buffer system compared with normal saline (NS), there have been no studies on the optimal fluid for surgery of an unruptured intracranial aneurysm (UIA). This study aimed to compare the effects of fluid regimens between NS and BC on the metabolic and clinical outcomes of patients who underwent surgery for UIA. METHODS: This study was designed as a propensity score matched retrospective comparative study and included adult patients who underwent UIA clipping. Patient groups were categorized as NS and BC groups based on the types of pre-operative fluid and the amount of fluid administered during surgery. The primary outcomes were defined as electrolyte imbalance and acidosis immediately after surgery. The secondary outcomes were the length of stay in the intensive care unit (ICU) and duration from the end of the operation to extubation. RESULTS: A total of 586 patients were enrolled in this study, with each of 293 patients assigned to the NS and BC groups, respectively. Immediately after surgery, serum chloride levels were significantly higher in the NS group. Compared to the NS group, the BC group had lower incidence rates of acidemia (6.5% vs. 11.6%, p=0.043) and metabolic acidosis (0.7% vs. 4.4%, p=0.007). As compared to NS group, BC group had significantly shorter duration from the end of the operation to extubation (250±824 vs. 122±372 minutes, p=0.016) and length of stay in ICU (1.37±1.11 vs. 1.12±0.61 days, p=0.001). Throughout multivariable analysis, use of BC was found to be significant factor for favorable post-operative results. CONCLUSION: This study showed that the patients who received BC during UIA clipping had lower incidence of metabolic acidosis, earlier extubation and shorter ICU stay compared to those who received NS. Therefore, using BC as a peri-operative fluid can be recommended for patients who undergo surgery for UIA.

Delayed Lesions on Diffusion-Weighted Imaging in Initially Lesion-Negative Stroke Patients.

BACKGROUND AND PURPOSE: Lesions on diffusion-weighted imaging (DWI) occasionally appear on follow-up magnetic resonance imaging (MRI) among initially DWI-negative but clinically suspicious stroke patients. We established the prevalence of positive conversion in DWI-negative stroke and determined the clinical factors associated with it. METHODS: This retrospective, observational, single-center study included 5,271 patients hospitalized due to stroke/transient ischemic attack (TIA) in a single university hospital during 2010 to 2017. Patients without initial DWI lesions underwent follow-up DWI imaging as a routine practice. Adjusted hazard ratios (aHRs) for recurrent stroke risk according to positive conversion were determined using Cox proportional hazard regression. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for positive conversion among initially DWI-negative patients were estimated. RESULTS: In total, 694 (13.2%) patients (mean±standard deviation age, 62.9±13.7 years; male, 404 [58.2%]) were initially DWI-negative. Among them, 22.5% had positive-conversion on follow-up DWI. Positive conversion was associated with a higher risk of recurrent stroke (aHR, 3.12; 95% CI, 1.56 to 6.26). Early neurologic deterioration (aOR, 15.1; 95% CI, 5.71 to 47.66), atrial fibrillation (aOR, 6.17; 95% CI, 3.23 to 12.01), smoking (aOR, 3.76; 95% CI, 2.19 to 6.63), pre-stroke dependency (aOR, 1.62; 95% CI, 1.15 to 2.27), objective hemiparesis (aOR, 4.39; 95% CI, 1.90 to 10.32), longer symptom duration (aOR, 2.17; 95% CI, 1.57 to 3.08), high cholesterol (aOR, 4.70; 95% CI, 1.78 to 12.77), National Institutes of Health Stroke Scale score (aOR, 1.44; 95% CI, 1.08 to 1.91), and high systolic blood pressure (aOR, 1.01; 95% CI, 1.00 to 1.02) were associated with a higher incidence of lesions with delayed appearance. Regarding the location of lesions on follow-up DWI, 34.6% and 21.2% were in the cortex and brainstem, respectively. CONCLUSIONS: In DWI-negative stroke/TIA, positive conversion is associated with a higher risk of recurrent stroke. DWI-negative stroke with factors related to positive conversion may require follow-up MRI for a definitive diagnosis.

In-Hospital and Post-Discharge Recovery after Acute Ischemic Stroke: a Nationwide Multicenter Stroke Registry-base Study.

BACKGROUND: Using data from a large national stroke registry, we aimed to investigate the incidence and determinants of in-hospital and post-discharge recovery after acute ischemic stroke and the independence of their occurrence. METHODS: In-hospital recovery was defined as an improvement of 4 points or > 40% in the National Institutes of Health Stroke Scale (NIHSS) score from admission to discharge. Post-discharge recovery was defined as any improvement in the modified Rankin Scale (mRS) score from discharge to 3 months after stroke onset. Two analytic methods (multivariate and multivariable logistic regression) were applied to compare the effects of 18 known determinants of 3-month outcome and to verify whether in-hospital and post-discharge recovery occur independently. RESULTS: During 54 months, 11,088 patients with acute ischemic stroke meeting the eligibility criteria were identified. In-hospital and post-discharge recovery occurred in 36% and 33% of patients, respectively. Multivariate logistic regression with an equality test for odds ratios showed that 7 determinants (age, onset-to-admission time, NIHSS score at admission, blood glucose at admission, systolic blood pressure, smoking, recanalization therapy) had a differential effect on in-hospital and post-discharge recovery in the way of the opposite direction or of the same direction with different degree (all P values < 0.05). Both in-hospital and post-discharge recovery occurred in 12% of the study population and neither of them in 43%. The incidence of post-discharge recovery in those with in-hospital recovery was similar to that in those without (33.8% vs. 32.7%, respectively), but multivariable analysis showed that these 2 types of recovery occurred independently. CONCLUSION: Our findings suggest that, in patients with acute ischemic stroke, in-hospital and post-discharge recovery may occur independently and largely in response to different factors.

Procedural and clinical outcomes of endovascular recanalization therapy in patients with cancer-related stroke.

Objective Embolism due to coagulopathy might be the main pathomechanism underlying cancer-related stroke (CRS). CRS patients with a large artery occlusion could be candidates for endovascular recanalization therapy (ERT), although its procedural and clinical outcomes are not well known. This study aimed to investigate the procedural and clinical outcomes of ERT in CRS patients and the characteristics associated with outcomes compared with those of conventional stroke patients. Methods A registry of consecutive acute ischemic stroke patients who underwent ERT between January 2011 and October 2015 was retrospectively reviewed. CRS patients are described as those who had (a) cryptogenic stroke with advanced or metastatic cancer; (b) no other possible causes of stroke such as cardioembolism (CE) and large artery atherosclerosis (LAA); and (c) elevated D-dimer levels or diffusion-restricted lesions in multiple vascular territories. We compared procedural and clinical outcomes at discharge among CRS, CE, and LAA patients. Results A total of 329 patients were finally enrolled in this study; of these, 19 were CRS patients. The rate of successful recanalization, defined as modified treatment in cerebral infarction grade 2b or 3, was lower in the CRS group than in the LAA and CE groups (63% versus 84% versus 84%, p = .06). CRS subtype was an independent predictor for successful recanalization after ERT in the multivariate analysis (odds ratio, 0.317; 95% confidence interval, 0.116-0.867; p < .001). No significant difference in the rate of good clinical outcomes at discharge was observed among groups. Conclusions Although clinical outcomes at discharge were similar for CE and LAA patients, complete recanalization seemed more difficult to achieve in CRS patients than in conventional stroke patients.

Temporal changes in the neutrophil to lymphocyte ratio and the neurological progression in cryptogenic stroke with active cancer.

BACKGROUND: Ischemic stroke patients with active cancer frequently experience early neurological deterioration (END); however, the predictors of END are not well studied. The neutrophil to lymphocyte ratio (NLR) has recently been described as a predictor of poor outcomes in cancer and stroke. However, its role in cancer-related stroke has not been addressed. AIM: We aimed to evaluate the association between the NLR and END in cancer-related stroke patients. METHODS: We included 85 cryptogenic stroke patients with active cancer. END was defined as an increase ≥ 4 on the total National Institutes of Health Stroke Scale (NIHSS) score within 72 hours of admission. The NLR was calculated as the ratio of the absolute neutrophil count to the absolute lymphocyte count. We obtained the NLR during the following three periods: at admission, 1-3 days after admission (D 1-3 NLR) and 4-7 days after admission (D 4-7 NLR). RESULTS: END occurred in 15 (18%) of the 85 patients. END was significantly associated with the initial NIHSS score, infarction volume, and the D 1-3 NLR. In multivariate analysis, a higher D 1-3 NLR, measured before END events, remained an independent predictor of END [adjusted odds ratio = 2.78, 95% confidence interval = 1.09-7.08, P = 0.032]. In terms of temporal changes in the NLR, the END group showed a tendency toward temporal increase in the NLR at D 1-3 (P = 0.061) with subsequent decrements in the D 4-7 NLR (P = 0.088), while the non-END group showed no significant changes in the NLR between periods. CONCLUSIONS: This study demonstrated that a higher NLR could predict END events in cryptogenic stroke patients with active cancer. However, the results should be confirmed in further large prospective studies.

Predictors of 30-day mortality and the risk of recurrent systemic thromboembolism in cancer patients suffering acute ischemic stroke.

BACKGROUND: Stroke in cancer patients is not rare but is a devastating event with high mortality. However, the predictors of mortality in stroke patients with cancer have not been well addressed. D-dimer could be a useful predictor because it can reflect both thromboembolic events and advanced stages of cancer. AIM: In this study, we evaluate the possibility of D-dimer as a predictor of 30-day mortality in stroke patients with active cancer. METHODS: We included 210 ischemic stroke patients with active cancer. The 30-day mortality data were collected by reviewing medical records. We also collected follow-up D-dimer levels in 106 (50%) participants to evaluate the effects of treatment response on D-dimer levels. RESULTS: Of the 210 participants, 30-day mortality occurred in 28 (13%) patients. Higher initial NIHSS scores, D-dimer levels, and CRP levels as well as frequent cryptogenic mechanism, systemic metastasis, multiple vascular territory lesion, hemorrhagic transformation, and larger infarct volume were related to 30-day mortality. In the multivariate analysis, D-dimer [adjusted OR (aOR) = 2.19; 95% CI, 1.46-3.28, P < 0.001] predicted 30-day mortality after adjusting for confounders. The initial NIHSS score (aOR = 1.07; 95% CI, 1.00-1.14, P = 0.043) and hemorrhagic transformation (aOR = 3.02; 95% CI, 1.10-8.29, P = 0.032) were also significant independent of D-dimer levels. In the analysis of D-dimer changes after treatment, the mortality group showed no significant decrease in D-dimer levels, despite treatment, while the survivor group showed the opposite response. CONCLUSIONS: D-dimer levels may predict 30-day mortality in acute ischemic stroke patients with active cancer.

Extended Use of Hypothermia in Elderly Patients with Malignant Cerebral Edema as an Alternative to Hemicraniectomy.

BACKGROUND AND PURPOSE: The use of decompressive hemicraniectomy (DHC) for the treatment of malignant cerebral edema can decrease mortality rates. However, this benefit is not sufficient to justify its use in elderly patients. We investigated the effects of therapeutic hypothermia (TH) on safety, feasibility, and functional outcomes in elderly patients with malignant middle cerebral artery (MCA) infarcts. METHODS: Elderly patients 60 years of age and older with infarcts affecting more than two-thirds of the MCA territory were included. Patients who could not receive DHC were treated with TH. Hypothermia was started within 72 hours of symptom onset and was maintained for a minimum of 72 hours with a target temperature of 33°C. Modified Rankin Scale (mRS) scores at 3 months following treatment and complications of TH were used as functional outcomes. RESULTS: Eleven patients with a median age of 76 years and a median National Institutes of Health Stroke Scale score of 18 were treated with TH. The median time from symptom onset to initiation of TH was 30.3±23.0 hours and TH was maintained for a median of 76.7±57.1 hours. Shivering (100%) and electrolyte imbalance (82%) were frequent complications. Two patients died (18%). The mean mRS score 3 months following treatment was 4.9±0.8. CONCLUSIONS: Our results suggest that extended use of hypothermia is safe and feasible for elderly patients with large hemispheric infarctions. Hypothermia may be considered as a therapeutic alternative to DHC in elderly individuals. Further studies are required to validate our findings.

Recurrent Stroke, Myocardial Infarction, and Major Vascular Events during the First Year after Acute Ischemic Stroke: The Multicenter Prospective Observational Study about Recurrence and Its Determinants after Acute Ischemic Stroke I.

BACKGROUND: Patients with acute ischemic stroke (AIS) are at high risk of subsequent vascular events. The aim of this study was to estimate rates of recurrent stroke, myocardial infarction (MI), and major vascular events during the first year after AIS in Korea. METHODS: Through a multicenter stroke registry in Korea, 12,227 consecutive cases of AIS were identified between November 2010 and May 2013 and were followed up for recurrent stroke, MI, and major vascular events up to 1 year after stroke. RESULTS: Cumulative 30-day, 90-day and 1-year rates were 2.7%, 3.9%, and 5.7% for recurrent stroke; .1%, .3%, and .5% for MI; and 8.1%, 10.6%, and 13.7% for major vascular events, indicating that the early period is at high risk of recurrent stroke and major vascular events. The risk of recurrent stroke was substantially higher than the risk of MI: 13.0 times at 90 days and 11.4 times at 1 year. Compared to those with small-vessel occlusion (SVO), those with ischemic stroke subtypes other than SVO had a higher risk of recurrent stroke as well as major vascular events. Other common independent predictors for recurrent stroke and major vascular events were diabetes and prior stroke history. CONCLUSIONS: During the first year after AIS, one in 18 had recurrent stroke and one in 7 major vascular events. More than two thirds of recurrent stroke and three quarters of major vascular events developed within 90 days in a Korean cohort of stroke patients. Better prevention strategies are required for high-risk patients during this high-risk period.

Identifying Target Risk Factors Using Population Attributable Risks of Ischemic Stroke by Age and Sex.

BACKGROUND AND PURPOSE: Estimating age- and sex-specific population attributable risks (PARs) of major risk factors for stroke may be a useful strategy to identify risk factors for targeting preventive strategies. METHODS: For this case-control matched study, consecutive patients aged 18-90 years and admitted to nine nationwide hospitals with acute ischemic stroke between December 2008 and June 2010, were enrolled as cases. Controls, individually matched by age and sex, were chosen from the 4th Korean National Health & Nutrition Examination Survey (2008-2010). Based on odds ratios and prevalence, standardized according to the age and sex structure of the Korean population, PARs of major risk factors were estimated according to age (young, ≤ 45; middle-aged, 46-65; and elderly, ≥ 66 years) and sex subgroups. RESULTS: In 4,743 matched case-control sets, smoking (PAR, 45.1%) was the greatest contributing risk factor in young men, followed by hypertension (28.5%). In middle-aged men, the greatest contributing factors were smoking (37.4%), hypertension (22.7%), and diabetes (14.6%), whereas in women the greatest factors were hypertension (22.7%) and stroke history (10.6%). In the elderly, hypertension was the leading factor in men (23.7%) and women (23.4%). Other noticeable factors were stroke history (men, 19.7%; women, 17.3%) and diabetes (men, 12.5%; women, 15.1%). In young women, risk factors with a PAR greater than 10% were not found. CONCLUSIONS: Smoking cessation in young people and hypertension and diabetes control in older people may be effective in reducing the burden of stroke on the population. In the elderly, secondary prevention could also be emphasized.

Early carotid artery stenting for symptomatic carotid artery stenosis.

BACKGROUND: The aim of present study was to assess safety and efficacy of early carotid artery stent (CAS) in patients with symptomatic carotid artery stenosis compared with delayed CAS. METHODS: This retrospective study was approved by the institutional review board, and the requirement to obtain written informed consent was waived. Outcomes of 206 patients with symptomatic carotid stenosis who were treated by CAS were analyzed. According to CAS timing from last symptom, patients were divided into early (within 2 weeks, 74 [35.0 %]) and delayed (after 2 weeks, 112 [64.1 %]) group by CAS timing from the last symptom. Procedural complication and early (≤30 days of CAS) event (ipsilateral stroke or any death) for safety, and late (31 days to 1 year of CAS) event for efficacy of CAS preventing further stroke were evaluated. The two groups were compared using Cox proportional hazard analysis. RESULTS: No difference was found in procedural complication between the groups (early 2 [2.7 %] vs. delayed group 7 [5.3 %], hazard ratio [HR] 0.61, 95 % confidence interval [CI] 0.123-2.979, p = 0.537). In the early group, however, early event developed more frequently than in the late group (9 [12.2 %] vs. 1 [0.8 %], HR 16.05, 95 % CI 1.991-129.438, p = 0.009). The late event rate showed no difference between the two groups (4 [5.4 %] vs. 4 [3.0 %], HR 2.09, 95 % CI 0.484-8.989, p = 0.324). CONCLUSIONS: Early CAS is not safe during periprocedural period, compared with late CAS. In CAS for symptomatic carotid stenosis, delayed CAS should be considered.

Dose-specific effect of simvastatin on hypoxia-induced HIF-1α and BACE expression in Alzheimer's disease cybrid cells.

BACKGROUND: Alzheimer's disease (AD) is associated with vascular risk factors; brain ischemia facilitates the pathogenesis of AD. Recent studies have suggested that the reduction of AD risk with statin was achieved by decreased amyloidogenic amyloid precursor protein. METHODS: We used mitochondrial transgenic neuronal cell (cybrid) models to investigate changes in the levels of intracellular hypoxia inducible factor 1α (HIF-1α) and ß-site amyloid precursor protein cleaving enzyme (BACE) in the presence of simvastatin. Sporadic AD (SAD) and age-matched control (CTL) cybrids were exposed to 2% O2 and incubated with 1 µM or 10 µM simvastatin. RESULTS: There was no significant difference between cell survival by 1 or 10 µM simvastatin in both SAD and CTL cybrids. In the presence of 1 µM simvastatin, intracellular levels of HIF-1α and BACE decreased by 40-70% in SAD, but not CTL cybrids. However, 10 µM simvastatin increased HIF-1α and BACE expression in both cybrid models. CONCLUSION: Our results suggest demonstrate differential dose-dependent effects of simvastatin on HIF-1α and BACE in cultured Alzheimer's disease cybrid cells.

Retinal and choroidal changes and visual outcome in central retinal artery occlusion: an optical coherence tomography study.

PURPOSE: To investigate the retinal and choroidal changes using spectral-domain optical coherence tomography (SD OCT) and to identify factors associated with visual outcome in eyes with central retinal artery occlusion (CRAO). DESIGN: Retrospective, observational case series. METHODS: setting: Institutional. PATIENTS: A total of 134 eyes diagnosed with acute (symptom onset ≤ 7 days) nonarteritic CRAO examined with SD OCT at baseline and follow-up visits. OBSERVATIONS: Based on funduscopic and angiographic findings, CRAO was categorized into 3 stages: incomplete, subtotal, and total. Abnormal morphologic features were evaluated from SD OCT images. Central macular thickness (CMT), inner and outer retinal thicknesses, and subfoveal choroidal thickness (SFCT) were measured. The clinical and SD OCT features were correlated with the final best-corrected visual acuities (BCVA). MAIN OUTCOME MEASURES: Retinal and choroidal thickness and BCVA. RESULTS: Features of SD OCT at the initial presentation included inner and outer retinal thickening. At baseline, the frequency of inner and outer retinal thickening and macular edema (CMT > 300 µm) differed significantly among CRAO stages (all P < .05). SFCT in eyes with total CRAO was significantly thinner compared with that of the contralateral eyes (P = .009). A higher CRAO stage was associated significantly with macular edema at baseline (P < .001) and retinal thinning at the final visit (P = .010). Baseline CMT was correlated significantly with final BCVA (P < .001). Multivariate logistic regression analyses revealed that severe vision loss (BCVA < 20/200) was associated significantly with CRAO stage (P < .001) and baseline CMT (P = .005). CONCLUSIONS: CRAO resulted in inner and outer retinal thickening in the acute stages and subsequent atrophic changes in the inner and outer retina. SD OCT may be a useful noninvasive imaging tool for diagnosis, staging, and prognosis of CRAO.

Internet-based control recruitment for a case-control study of major risk factors for stroke in Korea: lessons from the experience.

BACKGROUND: This study aimed to estimate the population-attributable risks (PARs) of 9 major risk factors for stroke in Korea through a case-control study and to test the feasibility and validity of internet-based control recruitment. METHODS: From April 2008 to September 2009, controls were enrolled via internet after providing consent for participation through a web-based survey. The cases included patients who were admitted to the participating centers due to acute stroke or transient ischemic attack within 7 days of onset during the study period. Each control was age- and sex-matched with 2 cases. Adjusted odd ratios, age-standardized prevalence, and PARs were estimated for the 9 major risk factors using the prevalence of risk factors in the control group and the age and sex characteristics from Korea's national census data. RESULTS: In total, 1041 controls were matched to 2082 stroke cases. Because of a shortage of elderly controls in the internet-based recruitment, 248 controls were recruited off-line. The PARs were 23.44%, 10.95%, 51.32%, and 6.35% for hypertension, diabetes, smoking, and stroke history, respectively. Hypercholesterolemia, atrial fibrillation, obesity, coronary heart disease, and a family history of stroke were not associated with stroke. Comparison with education and religion of the control group with that mentioned in the national census data showed a notable difference. CONCLUSIONS: The study results imply that internet-based control recruitment for a case-control study requires careful selection of risk factors with high self-awareness and effective strategies to facilitate the recruitment of elderly participants.