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1.
Ann Neurol ; 95(4): 788-799, 2024 Apr.
Article En | MEDLINE | ID: mdl-38381765

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.


Endovascular Procedures , Ischemic Stroke , Stroke , Humans , Basilar Artery , Treatment Outcome , Ischemic Stroke/etiology , Stroke/etiology , Thrombectomy/adverse effects , Intracranial Hemorrhages/etiology , Registries , Endovascular Procedures/adverse effects
2.
J Clin Neurol ; 20(1): 86-93, 2024 Jan.
Article En | MEDLINE | ID: mdl-38179636

BACKGROUND AND PURPOSE: Patients with cluster headache (CH) exhibit impaired health-related quality of life (HRQoL). However, there have been few studies related to the HRQoL of patients with CH from Asian backgrounds. This study aimed to determine the impact of CH on HRQoL and to identify the factors affecting HRQoL in patients with CH during cluster periods. METHODS: This prospective study enrolled patients with CH from 17 headache clinics in South Korea between September 2016 and February 2021. The study aimed to determine HRQoL in patients with CH using the EuroQol 5 Dimensions (EQ-5D) index and the time trade-off (TTO) method. Age- and sex-matched headache-free participants were recruited as a control group. RESULTS: The study included 423 patients with CH who experienced a cluster period at the time. EQ-5D scores were lower in patients with CH (0.88±0.43, mean±standard deviation) than in the controls (0.99±0.33, p<0.001). The TTO method indicated that 58 (13.6%) patients with CH exhibited moderate-to-severe HRQoL deterioration. The HRQoL states in patients with CH were associated with current smoking patterns, headache severity, frequency, and duration, and scores on the Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire 9-item scale (PHQ-9), 6-item Headache Impact Test, and 12-item Allodynia Symptom Checklist. Multivariable logistic regression analyses demonstrated that the HRQoL states in patients with CH were negatively correlated with the daily frequency of headaches, cluster period duration, and GAD-7 and PHQ-9 scores. CONCLUSIONS: Patients with CH experienced a worse quality of life during cluster periods compared with the headache-free controls, but the degree of HRQoL deterioration varied among them. The daily frequency of headaches, cluster period duration, anxiety, and depression were factors associated with HRQoL deterioration severity in patients with CH.

4.
J Neurointerv Surg ; 16(4): 352-358, 2024 Mar 14.
Article En | MEDLINE | ID: mdl-37197936

BACKGROUND: Thrombi retrieved from patients with acute ischemic stroke may contain prognostic information. OBJECTIVE: To investigate the relationship between the immunologic phenotype of thrombi and future vascular events in patients with a stroke. METHODS: This study included patients with acute ischemic stroke who underwent endovascular thrombectomy at Chung-Ang University Hospital in Seoul, Korea, between February 2017 and January 2020. Laboratory and histological variables were compared between patients with and without recurrent vascular events (RVEs). Kaplan-Meier analysis followed by the Cox proportional hazards model was used to identify factors related to RVE. Receiver operating characteristic (ROC) analysis was conducted to evaluate the performance of the immunologic score by combining immunohistochemical phenotypes to predict RVE. RESULTS: A total of 46 patients were included in the study with 13 RVEs (mean±SD age, 72.8±11.3 years; 26 (56.5%) men). Thrombi with a lower percentage of programmed death ligand-1 expression (HR=11.64; 95% CI 1.60 to 84.82) and a higher number of citrullinated histone H3 positive cells (HR=4.19; 95% CI 0.81 to 21.75) were associated with RVE. The presence of high-mobility group box 1 positive cell was associated with reduced risk of RVE, but the association was lost after adjustment for stroke severity. The immunologic score, which consists of the three immunohistochemical phenotypes, showed good performance in predicting RVE (area under the ROC curve, 0.858; 95% CI 0.758 to 0.958). CONCLUSIONS: The immunological phenotype of thrombi could provide prognostic information after stroke.


Brain Ischemia , Ischemic Stroke , Stroke , Thrombosis , Male , Humans , Middle Aged , Aged , Aged, 80 and over , Female , Ischemic Stroke/surgery , Ischemic Stroke/complications , Thrombosis/pathology , Cerebral Infarction/complications , Stroke/complications , Thrombectomy , Phenotype , Brain Ischemia/complications
5.
J Clin Lipidol ; 18(2): e207-e217, 2024.
Article En | MEDLINE | ID: mdl-38101971

BACKGROUND: Because ischemic stroke is heterogeneous, the associations between low-density lipoprotein (LDL)-cholesterol levels and early vascular outcomes might be different according to the stroke subtype in acute ischemic stroke patients. METHODS: This study was an analysis of a prospective, multicenter, stroke registry. Acute ischemic stroke patients previously not treated with statins were included. Admission LDL-cholesterol levels were divided into 7 groups at 20 mg/dl intervals for comparison. The primary early vascular outcome was a composite of stroke, myocardial infarction (MI) and all-cause mortality within 3 months. RESULTS: A total of 38,531 patients (age, 68.5 ± 12.8 yrs; male, 59.6%) were analyzed for this study. The 3-month cumulative incidences of the composite of stroke, MI, and all-cause mortality significantly differed among the LDL-cholesterol level groups, with the highest event rate (11.11%) in the lowest LDL-cholesterol group (<70 mg/dl). After adjustment, the U-shaped associations of LDL-cholesterol levels with primary outcome and all-cause mortality were observed. For the stroke subtypes, there were substantial interactions between the LDL-cholesterol groups and stroke subtype and all-cause mortality (Pinteraction=0.07). Different patterns, with higher risks of all-cause mortality in the lower LDL-cholesterol in the large artery atherosclerosis subtype (adjusted hazard ratio [aHR] 1.29, 95% confidence interval [CI] 0.98-1.69), but in the higher LDL-cholesterol in the cardioembolism subtype (aHR 1.71 95% CI [1.28-2.29]), were observed among stroke subtypes. CONCLUSION: We found that there were differential associations of admission LDL-cholesterol levels with all-cause mortality within 3 months among stroke subtypes. These results suggest that admission LDL-cholesterol and early vascular outcomes had complex relationships in patients with ischemic stroke according to the stroke subtypes.


Cholesterol, LDL , Ischemic Stroke , Humans , Male , Cholesterol, LDL/blood , Aged , Female , Ischemic Stroke/blood , Ischemic Stroke/mortality , Middle Aged , Prospective Studies , Myocardial Infarction/mortality , Myocardial Infarction/blood , Patient Admission , Aged, 80 and over , Brain Ischemia/mortality , Brain Ischemia/blood , Stroke/mortality , Stroke/blood
6.
J Am Heart Assoc ; 12(18): e030738, 2023 09 19.
Article En | MEDLINE | ID: mdl-37681519

Background It is unclear whether statin treatment could reduce the risk of early vascular events when baseline low-density lipoprotein cholesterol (LDL-C) levels are already low, at <70 mg/dL, at the time of the index stroke. Methods and Results This study was an analysis of a prospective, multicenter, nationwide registry of consecutive patients with first-ever acute ischemic stroke with baseline low-density lipoprotein cholesterol levels <70 mg/dL and without statin pretreatment. An inverse probabilities of treatment weights method was applied to control for imbalances in baseline characteristics. The primary outcome was a composite of stroke (either hemorrhagic or ischemic), myocardial infarction, and all-cause death within 3 months. A total of 2850 patients (age, 69.5±13.4 years; men, 63.5%) were analyzed for this study. In-hospital statin treatment was used for 74.2% of patients. The primary composite outcome within 3 months occurred in 21.5% of patients in the nonstatin group and 6.7% of patients in the statin group (P<0.001), but the rates of stroke (2.65% versus 2.33%), hemorrhagic stroke (0.16% versus 0.10%), and myocardial infarction (0.73% versus 0.19%) were not significantly different between the 2 groups. After inverse probability of treatment weighting analysis, the primary composite outcome was significantly reduced in patients with statin therapy (weighted hazard ratio [HR], 0.54 [95% CI, 0.42-0.69]). However, statin treatment did not increase the risk of hemorrhagic stroke (weighted HR, 1.11 [95% CI, 0.10-12.28]). Conclusions Approximately three-quarters of the patients with first-ever ischemic stroke with baseline low-density lipoprotein cholesterol levels <70 mg/dL received in-hospital statin treatment. Statin treatment, compared with no statin treatment, was significantly associated with a reduced risk of the 3-month primary composite outcomes and all-cause death but did not alter the rate of stroke recurrence.


Hemorrhagic Stroke , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Ischemic Stroke , Myocardial Infarction , Stroke , Male , Humans , Middle Aged , Aged , Aged, 80 and over , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Prospective Studies , Stroke/epidemiology , Stroke/prevention & control , Cholesterol, LDL , Myocardial Infarction/drug therapy , Myocardial Infarction/epidemiology
7.
J Clin Lipidol ; 17(5): 612-621, 2023.
Article En | MEDLINE | ID: mdl-37574400

BACKGROUND: Lipid paradox of low LDL-C may cause physicians to be reluctant to use statins in acute ischemic stroke (AIS) patients with low LDL-C levels at admission. OBJECTIVE: This study investigated the association between LDL-C levels and early vascular outcomes and assessed the potential interaction effect between LDL-C and statin pretreatment on early outcomes. PATIENTS AND METHODS: This was a study of a prospective, multicenter, registry of AIS patients with admission LDL-C. The subjects were divided into 3 groups according to LDL-C levels: low LDL-C (≤100 mg/dL); intermediate LDL-C (>100, <130 mg/dL); and high LDL-C (≥130 mg/dL). The primary early vascular outcome was a composite of stroke (ischemic or hemorrhagic), myocardial infarction and all-cause mortality within 3 months. The associations of LDL-C levels as a continuous variable and the risks of primary outcome using Cox proportional hazards models with restricted cubic splines were explored. RESULTS: A total of 32,505 patients (age, 69 ± 12; male, 58.6%) were analyzed. The 3 groups showed significant differences in the 3-month primary outcome, with highest events in the low LDL-C group; after adjustment, no significant associations with the 3-month primary outcome remained. U-shaped nonlinear relationships of LDL-C levels with the 3-month primary outcome were observed (Pnon-linearity<0.001), with substantial relationships in the no pretreatment subgroup. CONCLUSIONS: The relationships between admission LDL-C levels and early outcomes are complex but appear to be paradoxical in patients with low LDL-C and no statin pretreatment. The results suggest that statin pretreatment might offset the paradoxical response of low LDL-C on early vascular outcomes. Further study would be warranted.


Hydroxymethylglutaryl-CoA Reductase Inhibitors , Ischemic Stroke , Myocardial Infarction , Stroke , Humans , Male , Middle Aged , Aged , Aged, 80 and over , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Cholesterol, LDL , Ischemic Stroke/chemically induced , Prospective Studies , Stroke/drug therapy , Treatment Outcome
8.
Thromb Res ; 229: 219-224, 2023 09.
Article En | MEDLINE | ID: mdl-37562164

INTRODUCTION: The D-dimer to fibrinogen ratio (DFR) is a good indicator of clot-producing activity in thrombotic disease, but its clinical usefulness in stroke patients with nonvalvular atrial fibrillation (NVAF) has not been studied. We evaluated the association between the DFR and early neurological deterioration (END) in acute ischemic stroke (AIS) patients with NVAF. METHODS: We included consecutive AIS patients with NVAF between 2013 and 2015 from the registry of a real-world prospective cohort from 11 large centers in South Korea. END was defined as an increase ≥2 in the total NIHSS score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. The DFR was calculated as follows: DFR = D-dimer (mg/L)/fibrinogen (mg/dL) x 100. RESULTS: A total of 1018 AIS patients with NVAF were evaluated. In multivariable logistic regression analysis, the highest DFR tertile was closely associated with END (adjusted odds ratio [aOR] = 2.14, 95 % confidence interval [CI]: 1.24-3.69). Hypertension (aOR = 1.71, 95 % CI: 1.09-2.70), initial NIHSS score (aOR = 1.05, 95 % CI: 1.02-1.07) and use of anticoagulants (aOR = 0.41, 95 % CI: 0.28-0.60) were also correlated with END. In addition to END, the DFR was correlated with discharge NIHSS and modified Rankin Scale (mRS) scores and the 3-month mRS score. CONCLUSIONS: High DFR values were associated with END in AIS patients with NVAF. As the DFR is an indicator directly related to the main pathological mechanism of NVAF patients (fibrinolysis and coagulation), it may be useful in predicting their prognosis.


Atrial Fibrillation , Brain Ischemia , Ischemic Stroke , Stroke , Humans , Atrial Fibrillation/complications , Prospective Studies , Risk Factors , Stroke/complications , Fibrinogen , Brain Ischemia/complications
9.
Ann Neurol ; 94(6): 1155-1163, 2023 12.
Article En | MEDLINE | ID: mdl-37642641

OBJECTIVE: Functional and morphologic changes in extracranial organs can occur after acute brain injury. The neuroanatomic correlates of such changes are not fully known. Herein, we tested the hypothesis that brain infarcts are associated with cardiac and systemic abnormalities (CSAs) in a regionally specific manner. METHODS: We generated voxelwise p value maps of brain infarcts for poststroke plasma cardiac troponin T (cTnT) elevation, QTc prolongation, in-hospital infection, and acute stress hyperglycemia (ASH) in 1,208 acute ischemic stroke patients prospectively recruited into the Heart-Brain Interactions Study. We examined the relationship between infarct location and CSAs using a permutation-based approach and identified clusters of contiguous voxels associated with p < 0.05. RESULTS: cTnT elevation not attributable to a known cardiac reason was detected in 5.5%, QTc prolongation in the absence of a known provoker in 21.2%, ASH in 33.9%, and poststroke infection in 13.6%. We identified significant, spatially segregated voxel clusters for each CSA. The clusters for troponin elevation and QTc prolongation mapped to the right hemisphere. There were 3 clusters for ASH, the largest of which was in the left hemisphere. We found 2 clusters for poststroke infection, one associated with pneumonia in the left and one with urinary tract infection in the right hemisphere. The relationship between infarct location and CSAs persisted after adjusting for infarct volume. INTERPRETATION: Our results show that there are discrete regions of brain infarcts associated with CSAs. This information could be used to bootstrap toward new markers for better differentiation between neurogenic and non-neurogenic mechanisms of poststroke CSAs. ANN NEUROL 2023;94:1155-1163.


Brain Ischemia , Ischemic Stroke , Long QT Syndrome , Stroke , Humans , Ischemic Stroke/complications , Stroke/complications , Stroke/diagnostic imaging , Brain Ischemia/complications , Brain Ischemia/diagnostic imaging , Brain Infarction/complications , Troponin T , Long QT Syndrome/complications
10.
J Clin Neurol ; 19(5): 429-437, 2023 Sep.
Article En | MEDLINE | ID: mdl-37455504

BACKGROUND AND PURPOSE: The congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack (CHA2DS2-VASc) and hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol (HAS-BLED) scores have been validated in estimating the risks of ischemic stroke and major bleeding, respectively, in patients with atrial fibrillation (AF). This study investigated stroke-specific predictors of major bleeding in patients with stroke and AF who were taking oral anticoagulants (OACs). METHODS: Subjects were selected from patients enrolled in the Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts (K-ATTENTION) nationwide multicenter registry between 2013 and 2015. Patients were excluded if they were not taking OACs, had no brain imaging data, or had intracranial bleeding directly related to the index stroke. Major bleeding was defined according to International Society of Thrombosis and Haemostasis criteria. Cox regression analyses were performed to assess the associations between clinical variables and major bleeding and Kaplan-Meier estimates were performed to analyze event-free survival. RESULTS: Of a total of 3,213 patients, 1,414 subjects (mean age of 72.6 years, 52.5% males) were enrolled in this study. Major bleeding was reported in 34 patients during the median follow-up period of 1.73 years. Multivariable analysis demonstrated that initial National Institutes of Health Stroke Scale scores (hazard ratio [HR] 1.07, p=0.006), hypertension (HR 3.18, p=0.030), persistent AF type (HR 2.51, p=0.016), and initial hemoglobin level (HR 0.74, p=0.001) were independently associated with major bleeding risk. Except for hypertension, these associations remained significant after adjusting for the HAS-BLED score. Intracranial atherosclerosis presented a trend of association without statistical significance (HR 2.21, p=0.050). CONCLUSIONS: This study found that major bleeding risk was independently associated with stroke-specific factors in anticoagulated patients with stroke and AF. This has the clinical implication that baseline characteristics of patients with stroke and AF should be considered in secondary prevention, which would bring the net clinical benefit of balancing recurrent stroke prevention with minimal bleeding complications.

11.
J Clin Neurol ; 19(3): 327, 2023 May.
Article En | MEDLINE | ID: mdl-37151146

This corrects the article on p. 28 in vol. 19, PMID: 36606643.

12.
J Stroke ; 25(2): 242-250, 2023 May.
Article En | MEDLINE | ID: mdl-37032475

BACKGROUND AND PURPOSE: Moderate-intensity statin plus ezetimibe versus high-intensity statin alone may provide a greater low-density lipoprotein cholesterol (LDL-C) reduction in patients with recent ischemic stroke. METHODS: This randomized, open-label, controlled trial assigned patients with recent ischemic stroke <90 days to rosuvastatin/ezetimibe 10/10 mg once daily (ROS10/EZT10) or to rosuvastatin 20 mg once daily (ROS20). The primary endpoint was LDL-C reduction ≥50% from baseline at 90 days. Key secondary endpoints were LDL-C <70 mg/dL and multiple lipid goal achievement, and composite of major vascular events. RESULTS: Of 584 randomized, 530 were included in the modified intention-to-treat analysis. The baseline LDL-C level was 130.2±34.7 mg/dL in the ROS10/EZT10 group and 131.0±33.9 mg/dL in the ROS20 group. The primary endpoint was achieved in 198 patients (72.5%) in the ROS10/EZT10 group and 148 (57.6%) in the ROS20 group (odds ratio [95% confidence interval], 1.944 [1.352-2.795]; P= 0.0003). LDL-C level <70 mg/dL was achieved in 80.2% and 65.4% in the ROS10/EZT10 and ROS20 groups (P=0.0001). Multiple lipid goal achievement rate was 71.1% and 53.7% in the ROS10/EZT10 and ROS20 groups (P<0.0001). Major vascular events occurred in 1 patient in the ROS10/EZT10 group and 9 in the ROS20 group (P=0.0091). The adverse event rates did not differ between the two groups. CONCLUSION: Moderate-intensity rosuvastatin plus ezetimibe was superior to high-intensity rosuvastatin alone for intensive LDL-C reduction in patients with recent ischemic stroke. With the combination therapy, more than 70% of patients achieved LDL-C reduction ≥50% and 80% had an LDL-C <70 mg/dL at 90 days.

13.
Cephalalgia ; 43(4): 3331024231159627, 2023 04.
Article En | MEDLINE | ID: mdl-36855967

BACKGROUND: Only limited data are available regarding the treatment status and response to cluster headache in an Asian population. Therefore, this study aimed to provide a real-world treatment pattern of cluster headache and the response rate of each treatment in an Asian population. METHODS: Patients with cluster headache were recruited between September 2016 and January 2019 from 16 hospitals in Korea. At the baseline visit, we surveyed the patients about their previous experience of cluster headache treatment, and acute and/or preventive treatments were prescribed at the physician's discretion. Treatment response was prospectively evaluated using a structured case-report form at 2 ± 2 weeks after baseline visit and reassessed after three months. RESULTS: Among 295 recruited patients, 262 experiencing active bouts were included. Only one-third of patients reported a previous experience of evidence-based treatment. At the baseline visit, oral triptans (73.4%), verapamil (68.3%), and systemic steroids (55.6%) were the three most common treatments prescribed by the investigators. Most treatments were given as combination. For acute treatment, oral triptans and oxygen were effective in 90.1% and 86.8% of the patients, respectively; for preventive treatment, evidence-based treatments, i.e. monotherapy or different combinations of verapamil, lithium, systemic steroids, and suboccipital steroid injection, helped 75.0% to 91.8% of patients. CONCLUSION: Our data provide the first prospective analysis of treatment responses in an Asian population with cluster headache. The patients responded well to treatment despite the limited availability of treatment options, and this might be attributed at least in part by combination of medications. Most patients were previously undertreated, suggesting a need to raise awareness of cluster headache among primary physicians.


Cluster Headache , Humans , Cluster Headache/drug therapy , Oxygen , Tryptamines , Verapamil , Republic of Korea/epidemiology
14.
Int J Stroke ; 18(8): 1015-1020, 2023 10.
Article En | MEDLINE | ID: mdl-36974902

RATIONALE: The optimal duration of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin for the large artery atherosclerotic (LAA) stroke subtype has been debated. AIMS: To determine whether the 1-year risk of recurrent vascular events could be reduced by a longer duration of DAPT in patients with the LAA stroke subtype. METHODS AND STUDY DESIGN: A total of 4806 participants will be recruited to detect a statistically significant relative risk reduction of 22% with 80% power and a two-sided alpha error of 0.05, including a 10% loss to follow-up. This is a registry-based, multicenter, prospective, randomized, open-label, blinded end point study designed to evaluate the efficacy and safety of a 12-month duration of DAPT compared with a 3-month duration of DAPT in the LAA stroke subtype. Patients will be randomized (1:1) to either DAPT for 12 months or DAPT for 3 months, followed by monotherapy (either aspirin or clopidogrel) for the remaining 9 months. STUDY OUTCOMES: The primary efficacy outcome of the study is a composite of stroke (ischemic or hemorrhagic), myocardial infarction, and all-cause mortality for 1 year after the index stroke. The secondary efficacy outcomes are (1) stroke, (2) ischemic stroke or transient ischemic attack, (3) hemorrhagic stroke, and (4) all-cause mortality. The primary safety outcome is major bleeding. DISCUSSION: This study will help stroke physicians determine the appropriate duration of dual therapy with clopidogrel-aspirin for patients with the LAA stroke subtype. TRIAL REGISTRATION: URL: https://cris.nih.go.kr/cris. CRIS Registration Number: KCT0004407.


Atherosclerosis , Ischemic Stroke , Stroke , Humans , Platelet Aggregation Inhibitors/therapeutic use , Clopidogrel/therapeutic use , Stroke/etiology , Ischemic Stroke/drug therapy , Prospective Studies , Drug Therapy, Combination , Aspirin/therapeutic use , Hemorrhage/chemically induced , Atherosclerosis/complications , Atherosclerosis/drug therapy , Treatment Outcome
15.
Contemp Clin Trials ; 126: 107108, 2023 03.
Article En | MEDLINE | ID: mdl-36724841

BACKGROUND: Oxiracetam may have a modest effect on preventing cognitive decline. Exercise can also enhance cognitive function. This trial aims to investigate the effect of oxiracetam on post-stroke cognitive impairment and explore whether this effect is modified by exercise. Furthermore, the mechanisms that mediate this effect will be investigated through a neural network analysis. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled phase IV trial. Patients who complained of cognitive decline 3 months after stroke and had a high risk of cognitive decline were eligible. Patients were randomly assigned to receive either 800 mg of oxiracetam or placebo twice daily for 36 weeks. After randomization, a predetermined exercise protocol was provided to each participant, and the degree of physical activity was assessed using wrist actigraphy at 4, 12, 24, and 36 weeks. Resting-state functional MRI was obtained in baseline and 36-week follow-up. Co-primary endpoints are changes in the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes. Secondary endpoints include changes in the NINDS-CSN VCIHS-Neuropsychology Protocol, Euro QoL, patient's global assessment, and functional network connectivity. If there is a significant difference in physical activity between the two groups, the interaction effect between physical activity and the treatment group will be examined. A total of 500 patients were enrolled from February 2018, and the last patient's final follow-up was completed in September 2022. CONCLUSION: This trial is meaningful not only to prove the efficacy of oxiracetam, but also evaluate whether exercise can modify the effects of medication and how cognitive function can be restored. Trial registrationhttp://cris.nih.go.kr (KCT0005137).


Cognitive Dysfunction , Stroke , Humans , Quality of Life , Cognitive Dysfunction/drug therapy , Pyrrolidines/therapeutic use , Double-Blind Method , Treatment Outcome
16.
J Clin Neurol ; 19(1): 28-35, 2023 Jan.
Article En | MEDLINE | ID: mdl-36606643

BACKGROUND AND PURPOSE: We investigated whether circulating microRNAs (miRNAs) is associated with arterial stiffness in patients with acute ischemic stroke. METHODS: We recruited patients with acute ischemic stroke who were admitted to a university hospital stroke center and underwent carotid-femoral pulse wave velocity (cfPWV) measurement using SphygmoCor (AtCor Medical, Sydney, Australia) and brachial-ankle PWV using a volume-plethysmography device (VP-1000, Omron Colin, Komaki, Japan). Circulating miRNAs were measured in venous blood samples stored in EDTA. We selected five miRNAs (miR-17, miR-93, miR-450, miR-629, and let-7i) related to atherosclerosis based on a literature review. Pearson's correlation analysis was applied to the correlations between miRNAs and arterial stiffness parameters. Finally, multivariable linear regression analysis was performed to identify the independent factors for cfPWV. RESULTS: This study included 70 patients (age=71.1±10.3 years [mean±SD], 29 females). The expression levels of miR-93 (r=-0.27, p=0.049) and let-7i (r=-0.27, p=0.039) were inversely correlated with cfPWV. Multivariable linear regression analysis including age, hypertension, and estimated glomerular filtration rate showed that let-7i was independently related with cfPWV (standardized coefficient=-0.262, p=0.036). Correlation analysis indicated that let-7i was positively associated with visceral muscle Hounsfield units on computed tomography (r=0.264, p=0.043). CONCLUSIONS: The expression level of let-7i was independently related to arterial stiffness in patients with cerebral infarction, suggesting that it plays a pathophysiological role in atherosclerosis.

17.
Circ Cardiovasc Imaging ; 16(1): e014544, 2023 01.
Article En | MEDLINE | ID: mdl-36649457

BACKGROUND: Elevated metabolic activity of amygdala is known to be related to atherosclerotic cardiovascular event by increasing inflammatory cell production from bone marrow. We tried to identify the factors of metabolic activity in the amygdala, vertebrae, liver, spleen, and internal carotid artery related to the future vascular events after stroke. METHODS: A total of 110 patients with acute stroke were included (72±10 years of age, 39% women) and underwent whole-body 18F-fluorodeoxyglucose (FDG) positron emission tomography between August 1, 2015 and February 28, 2020. We compared the FDG uptake in the amygdala, vertebrae, liver, spleen, and internal carotid artery between patients with and without recurrent vascular event. Cox proportional hazards model was used to identify factors related to recurrent stroke and vascular event. RESULTS: During the median follow-up period of 18 months, 22 patients experienced vascular events, including 15 stroke recurrence. Patients with recurred vascular event had a significantly higher FDG uptake in the amygdala and vertebrae than those without. The Cox proportional hazard model including diabetes, renal function, and carotid stenosis showed that a higher FDG uptake in the amygdala was independently associated with total vascular events (hazard ratio, 3.11 [95% CI, 1.11-8.70]) and higher FDG uptake in the vertebrae with stroke recurrence (hazard ratio, 4.94 [95% CI, 1.29-18.9]). CONCLUSIONS: The increased metabolic activities of the vertebrae and amygdala are related to future vascular event among stroke survivors.


Fluorodeoxyglucose F18 , Stroke , Humans , Female , Male , Prospective Studies , Stroke/diagnostic imaging , Stroke/etiology , Positron-Emission Tomography , Spine , Amygdala , Radiopharmaceuticals
18.
Sci Rep ; 12(1): 22543, 2022 12 29.
Article En | MEDLINE | ID: mdl-36581672

Positron emission tomography with 18F-sodium fluoride (NaF) radioligand has been actively investigated in atherosclerosis research because it is known to detect microcalcification activity within atheroma. We studied whether NaF shows any uptake in the brain tissue of patients with acute ischemic stroke. This is a post-hoc analysis of previously reported cerebral atherosclerosis research with positron emission tomography which applied the two radioligands, 18F-fluorodeoxyglucose and NaF for the detection of culprit atheroma among 20 acute cerebral infarction patients (mean age = 75.1 ± 9.0 years; 10 women). In this study, we measured the maximum and mean standardized uptake value (SUVmax and SUVmean) of NaF uptake level in the cerebral infarct region between lesions with and without diffusion weighted image (DWI) positivity, indicating acute ischemic cell death. Correlation analysis was performed between NaF uptake levels and imaging and clinical variables, including neurological severity. The NaF uptake levels were significantly higher in DWI positive lesions than in negative lesions (SUVmax: 2.0 [0.60-4.2] versus 0.20 [0.10-0.40], p = 0.021 by Mann-Whitney U test). The intensity of NaF uptake (SUVmax) was significantly correlated with the initial neurological severity (Spearman's ρ = 0.579, p= 0.007) and white blood cell count (Spearman's ρ = 0.626, p p 0.003). During ischemic stroke NaF was concentrated in brain tissue undergoing acute cell death and its uptake intensity was correlated with neurological severity, suggesting that NaF could reflect acute ischemic cell death after stroke.


Ischemic Stroke , Plaque, Atherosclerotic , Stroke , Humans , Female , Aged , Aged, 80 and over , Sodium Fluoride , Plaque, Atherosclerotic/diagnosis , Positron Emission Tomography Computed Tomography/methods , Tomography, X-Ray Computed , Positron-Emission Tomography , Cerebral Infarction/diagnostic imaging , Brain/diagnostic imaging , Brain/metabolism , Fluorine Radioisotopes
19.
High Blood Press Cardiovasc Prev ; 29(6): 595-600, 2022 Nov.
Article En | MEDLINE | ID: mdl-36166186

INTRODUCTION: Amlodipine belongs to a class of calcium channel blockers that relax blood vessels to allow easier flow of blood. Higher blood pressure (BP) is associated with cerebrovascular disease and is an important contributor to cognitive decline and dementia. AIM: This study aimed to evaluate the effect of 24 weeks of S-amlodipine besylate therapy on cognitive function in patients with hypertension and cerebrovascular disease. METHODS: The data were obtained from a study of post-market surveillance of S-amlodipine besylate. RESULTS: A total of 545 subjects (mean age 67 ± 9.68 years) with hypertension and ischemic cerebrovascular disease were enrolled. Patients with a baseline Mini-Mental State Examination (MMSE) score above 26 were assigned to the cognitive normal (CN) (n = 294) group, and those with MMSE score less than 26 were in the cognitive decline (CD) (n = 251) group. After 24 weeks of treatment with S-amlodipine besylate 5 mg, MMSE and Global Deterioration Scale (GDS) were evaluated again. Changes in MMSE were compared in the target BP reached (TBPR) and non-reached (NTBPR) groups and for CN and CD groups. Treatment with 5 mg of S-amlodipine besylate for 24 weeks improved MMSE and GDS scores (p < 0.001). The CD group showed improvement in MMSE score regardless of whether target BP was obtained (TBPR: p < 0.001, NTBPR: p < 0.01). However, the CN classification was not significant for either TBPR or NTBPR groups. CONCLUSIONS: S-amlodipine besylate improved cognition of the CD group with hypertension and cerebrovascular disease regardless of obtaining target BP.


Cerebrovascular Disorders , Cognitive Dysfunction , Hypertension , Humans , Middle Aged , Aged , Calcium Channel Blockers/adverse effects , Antihypertensive Agents/adverse effects , Blood Pressure , Double-Blind Method , Amlodipine/adverse effects , Hypertension/diagnosis , Hypertension/drug therapy , Cerebrovascular Disorders/diagnosis , Cerebrovascular Disorders/drug therapy , Cerebrovascular Disorders/etiology , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Cognition
20.
J Stroke Cerebrovasc Dis ; 31(10): 106706, 2022 Oct.
Article En | MEDLINE | ID: mdl-35985145

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.


Atrial Fibrillation , Stroke , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Humans , Proportional Hazards Models , Risk Factors , Stroke/complications , Stroke/diagnosis , Stroke/epidemiology , Thinness/diagnosis , Thinness/epidemiology
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