A Case of Recurrent Ischemic Stroke Associated with Immunoglobulin G4-Related Disease

Immunoglobulin G4-related disease (IgG4 RD) is a systemic immune-mediated inflammatory disease that presents as multiple organ dysfunction or mass lesions with lympho-plasmacytic infiltration. However, there are few case reports presenting central nervous system involvements. Herein, we report a case of a 70-year-old man with recurrent ischemic stroke which induced by IgG4 RD. IgG4 RD should be considered and treated as one of etiologies manifesting small vessel disease infarctions, especially when it occurs multiply and recurrently.

Changes in High-Density Lipoprotein Cholesterol and Risks of Cardiovascular Events: A Post Hoc Analysis from the PICASSO Trial / 대한뇌졸중학회지

Background@#and purpose Whether pharmacologically altered high-density lipoprotein cholesterol (HDL-C) affects the risk of cardiovascular events is unknown. Recently, we have reported the Prevention of Cardiovascular Events in Asian Patients with Ischaemic Stroke at High Risk of Cerebral Haemorrhage (PICASSO) trial that demonstrated the non-inferiority of cilostazol to aspirin and superiority of probucol to non-probucol for cardiovascular prevention in ischemic stroke patients (clinicaltrials.gov: NCT01013532). We aimed to determine whether on-treatment HDL-C changes by cilostazol and probucol influence the treatment effect of each study medication during the PICASSO study. @*Methods@#Of the 1,534 randomized patients, 1,373 (89.5%) with baseline cholesterol parameters were analyzed. Efficacy endpoint was the composite of stroke, myocardial infarction, and cardiovascular death. Cox proportional hazards regression analysis examined an interaction between the treatment effect and changes in HDL-C levels from randomization to 1 month for each study arm. @*Results@#One-month post-randomization mean HDL-C level was significantly higher in the cilostazol group than in the aspirin group (1.08 mmol/L vs. 1.00 mmol/L, P<0.001). The mean HDL-C level was significantly lower in the probucol group than in the non-probucol group (0.86 mmol/L vs. 1.22 mmol/L, P<0.001). These trends persisted throughout the study. In both study arms, no significant interaction was observed between HDL-C changes and the assigned treatment regarding the risk of the efficacy endpoint. @*Conclusions@#Despite significant HDL-C changes, the effects of cilostazol and probucol treatment on the risk of cardiovascular events were insignificant. Pharmacologically altered HDL-C levels may not be reliable prognostic markers for cardiovascular risk.

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

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

Hippocampal Hyperintensities on Diffusion-Weighted MRI without Transient Global Amnesia

Dot-like hippocampal hyperintensities on diffusion-weighted magnetic resonance imaging (MRI) have been reported as an interesting imaging finding of transient global amnesia (TGA). We report three patients with such dot-like hippocampal hyperintensities who did not present with anterograde amnesia. Episodes associated with the Valsalva maneuver such as nausea or vomiting might have produced the dot-like hippocampal hyperintensities in these patients. However, depending on the individual susceptibility to hippocampal lesions, clinical symptoms of TGA might not be present even when hippocampal lesions are present.

Clinical Characteristics of Cerebral Venous Thrombosis in a Single Center in Korea

OBJECTIVE: The purpose of this study is to investigate the clinical characteristics of cerebral venous thrombosis (CVT) in a single center in Korea. METHODS: A total of 36 patients were diagnosed with CVT from August 2005 to May 2013. The patient data regarding age, sex, disease stage, pathogenesis, location, laboratory findings, radiological findings, and treatment modalities were retrospectively collected. The results were compared with those of previous studies in other countries. RESULTS: The patient group comprised 21 men and 15 women with a mean age of 46.9 years (ranging from three months to 77 years). The most common cause was a prothrombotic condition (8 patients, 22.2%). Within the patient group, 13 patients (36.1%) had a hemorrhagic infarction, whereas 23 (63.9%) had a venous infarction without hemorrhage. By location, the incidence of hemorrhagic infarction was the highest in the group with a transverse and/or sigmoid sinus thrombosis (n=9); however, the proportion of hemorrhagic infarction was higher in the cortical venous thrombosis group (75%) and the deep venous thrombosis group (100%). By pathogenesis, the incidence of hemorrhagic infarction was the highest in the prothrombotic group (n=6), which was statistically significant (p=0.016). CONCLUSION: According to this study, CVT was more prevalent in men, and the peak age group comprised patients in the sixth decade. The most common cause was a prothrombotic condition. This finding was comparable with reports from Europe or America, in which CVT was more common in younger women. Hemorrhagic infarction was more common in the prothrombotic group (p=0.016) than in the non-prothrombotic group in this study.

Transcriptional Upregulation of Plasminogen Activator Inhibitor-1 in Rat Primary Astrocytes by a Proteasomal Inhibitor MG132

Plasminogen activator inhibitor-1 (PAI-1) is a member of serine protease inhibitor family, which regulates the activity of tissue plasminogen activator (tPA). In CNS, tPA/PAI-1 activity is involved in the regulation of a variety of cellular processes such as neuronal development, synaptic plasticity and cell survival. To gain a more insights into the regulatory mechanism modulating tPA/PAI-1 activity in brain, we investigated the effects of proteasome inhibitors on tPA/PAI-1 expression and activity in rat primary astrocytes, the major cell type expressing both tPA and PAI-1. We found that submicromolar concentration of MG132, a cell permeable peptide-aldehyde inhibitor of ubiquitin proteasome pathway selectively upregulates PAI-1 expression. Upregulation of PAI-1 mRNA as well as increased PAI-1 promoter reporter activity suggested that MG132 transcriptionally increased PAI-1 expression. The induction of PAI-1 downregulated tPA activity in rat primary astrocytes. Another proteasome inhibitor lactacystin similarly increased the expression of PAI-1 in rat primary astrocytes. MG132 activated MAPK pathways as well as PI3K/Akt pathways. Inhibitors of these signaling pathways reduced MG132-mediated upregulation of PAI-1 in varying degrees and most prominent effects were observed with SB203580, a p38 MAPK pathway inhibitor. The regulation of tPA/PAI-1 activity by proteasome inhibitor in rat primary astrocytes may underlie the observed CNS effects of MG132 such as neuroprotection.

Review of Evidences and Updates of the Korean Clinical Practice Guidelines for Stroke in 2013

The first edition of Korean Clinical Practice Guidelines for Stroke, which was published in 2009, reflected evidence published prior to June 2007. Since then, many clinical trials and well-designed observational studies provided new evidence that may be pertinent to clinical practice. Accordingly, investigators of the Clinical Research Center for Stroke have timely updated the guidelines. This article summarizes the recent evidence and updated guidelines regarding the use of aspirin for primary stroke prevention, the management of asymptomatic carotid stenosis, the use of antithrombotics in atrial fibrillation for stroke prevention, the diagnosis and management of unruptured aneurysm, intravenous and intra-arterial thrombolysis in acute ischemic stroke, antiplatelet therapy for secondary stroke prevention in patients with non-cardioembolic stroke or transient ischemic attack, and the management of symptomatic carotid stenosis for secondary stroke prevention.

Clinical Characteristics of Chronic Headache Patients With Fibromyalgia: A Hospital-based Study

BACKGROUND: Fibromyalgia (FM) is a chronic diffuse pain syndrome of unknown etiology. FM is commonly associated with various neurological symptoms and signs including headache, non-restorative sleep, fatigue, and cognitive dysfunction. The purpose of this study is to investigate the clinical features of chronic daily headache patients with FM comorbidity. METHODS: Outpatients with chronic daily headache were recruited. FM was diagnosed on the basis of 2010 American College of Rheumatology criteria. We analyzed clinical features of the patients with FM and which general somatic symptoms were common in them. RESULTS: Of the 70 patients with chronic headache, 22 (about 31%) met the new ACR criteria of FM. Most of them were female, and their headache was likely to be tension type. Paresthesia, itching, and heartburn were significantly common in the headache patients with FM. CONCLUSIONS: Our study showed that a significant proportion of female patients with chronic tension type headache had chance to have FM. While taking history from patients with headache, neurologists should concern other somatic symptoms of FM as well as headache itself. Identification of FM in chronic headache patients may help more efficient treatment for the headache.

The Response of Carotid Intima-Media Thickness to Medical Treatment Is Correlated with That of Intracranial Atherosclerosis

BACKGROUND AND PURPOSE: Intracranial atherosclerotic stenosis (ICAS) is considered as a major cause of stroke. The carotid intima-media thickness (CIMT), which accurately reflects the burden of generalized atherosclerosis, is also associated with stroke. The aim of this study was to determine the association between the CIMT and ICAS responses to medical treatment. METHODS: This study constituted part of the "Trial of cilostazol in symptomatic intracranial arterial stenosis"-2 that evaluated the ICAS response after randomized antiplatelet treatment. Magnetic resonance angiography and CIMT measurement were performed at baseline and after 7 months of treatment. CIMT was measured using semiautomated software, and was presented as maximum (CIMT-max) and average (CIMT-ave) values. The change in CIMT was compared relative to the ICAS response (i.e., progression, no-change, and regression). Ordinal logistic regression and analysis of covariance (ANCOVA) were used to analyze the association between the responses. RESULTS: Among the 101 enrolled patients, 85 underwent follow-up CIMT measurement. CIMT increased most in the ICAS progression group (CIMT-max: 0.09+/-0.23, CIMT-ave: 0.04+/-0.12), and to a lesser degree in the no-change group (CIMT-max: 0.02+/-0.16, CIMT-ave: 0.02+/-0.11), but decreased in patients with ICAS regression (CIMT-max: -0.04+/-0.11, CIMT-ave: -0.03+/-0.07; CIMT-max: p=0.010, CIMT-ave: p=0.015). Ordinal logistic regression analysis demonstrated that the change in CIMT-max was independently associated with the ICAS response (p=0.032). However, the ANCOVA revealed that the reverse was not true, in that the ICAS response was not independently associated with the change in CIMT after adjusting for confounding factors. CONCLUSIONS: The ICAS response may be associated with the CIMT response to medical treatment.

Critical Appraisal of SCAST Study / 대한뇌졸중학회지

No abstract available.

Thyroid Incidentaloma Detected by Time-Resolved Magnetic Resonance Angiography at 3T: Prevalence and Clinical Significance

OBJECTIVE: To determine the prevalence of thyroid incidentalomas detected by time-resolved magnetic resonance angiography (TRMRA) and to evaluate their clinical significance by using an ultrasonographic (US) and cytologic correlation. MATERIALS AND METHODS: We retrospectively reviewed 2010 consecutive TRMRA examinations performed at our institution between August 2006 and April 2010. The TRMRA findings of thyroid incidentalomas were analyzed according to location, size, as well as vascularity, and were correlated with the US findings and cytologic results. Each nodule was classified as suspiciously malignant, indeterminate or probably benign according to the US criteria recommended by the Korean Society of Thyroid Radiology. RESULTS: A total of 102 incidentalomas were detected in 90 of 2010 patients (5%). TRMRA showed homogenous hypervascularity in 48 (47%), inhomogeneous hypervascularity in 46 (45%), and hypovascularity in 8 (8%) thyroid nodules. At follow-up study, out of 26 patients with 30 incidentalomas on TRMRA, 27 nodules were identified on US. Of the 27 nodules, 24 (89%) nodule were classified as indeterminate, two (7%) as probably benign, and one (4%) as suspiciously malignant. Among the 16 nodules with available cytopathologic results, 14 (82%) were benign, one (6%) was indeterminate, and one (6%) was malignant. CONCLUSION: Thyroid incidentalomas are found in 5% of TRMRA examinations. Although their presence does not necessarily indicate malignancy, nonspecific findings of detected incidentalomas on TRMRA require further evaluation by US.

Focused Update on Primary Stroke Prevention in Patients with Atrial Fibrillation in Korean Clinical Practice Guidelines for Stroke / 대한뇌졸중학회지

Pivotal clinical trials testing the efficacy of new antithrombotics for the prevention of stroke and systemic embolism in patients with atrial fibrillation have been published since the release of the first edition of Korean clinical practice guidelines for primary stroke prevention. From July 2007 to August 2012, 5 clinical studies and update of guidelines in Europe and North America were identified through systematic search. In patients with atrial fibrillation who were unsuitable for warfarin, the combination of clopidogrel and aspirin reduced the risk of stroke at the cost of increased major bleedings as compared to aspirin. In patients with nonvalvular atrial fibrillation and risk factors for stroke, new oral anticoagulants, dabigatran, rivaroxaban and apixaban, were as effective as or more effective than warfarin in preventing stroke or systemic embolism. The risks of major bleeding with novel anticoagulants were similar to or lower than that of warfarin. Particularly, the risk of intracranial bleeding was significantly lower with novel anticoagulants than with warfarin. In this report, we summarized the new evidences and updated our recommendations for primary stroke prevention in patients with atrial fibrillation.

2011 Update of Scientific Statement for the Primary Prevention of Stroke: Dyslipidemia and Inflammation

BACKGROUND: This scientific statement is intended to provide a systematic review of new evidences in dyslipidemia and inflammation for primary stroke prevention. METHODS: Using a structured literature search, we identified major observational studies, clinical trials, meta-analyses, and updated major guidelines published between July 2007 and November 2010. In addition to the brief summary of earlier evidences employed in the first edition of Korean clinical practice guideline for primary prevention of stroke, we summarized the newly identified evidences. RESULTS: For dyslipidemia, observational studies further support a strong association between ischemic stroke and high total and low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol. Two clinical trials and 6 meta-analyses confirm statin efficacy for primary prevention of stroke in high risk patients. Efficacy of other lipid-lowering agents is not established. For inflammation, inflammatory markers might help to identify patients having high risk for stroke or cardiovascular event and to decide whether statin therapy is indicated, but its usefulness for broad population needs to be confirmed. CONCLUSIONS: Writing committee will continue to keep an eye on upcoming evidences to timely update the guideline for primary stroke prevention in dyslipidemia and inflammation.

Management of Asymptomatic Carotid Stenosis for Primary Stroke Prevention: 2012 Focused Update of Korean Clinical Practice Guidelines for Stroke

Extracranial carotid stenosis is a well-established, modifiable risk factor for stroke. Asymptomatic extracranial carotid stenosis is increasingly being detected due to the introduction of less-invasive and more-sensitive advanced diagnostic technologies. For severe asymptomatic stenosis, earlier pivotal clinical trials demonstrated the benefit of carotid endarterectomy over the best medical therapy. Since then, great advances have been made in interventional and medical therapies as well as surgical techniques. The first edition of the Korean Stroke Clinical Practice Guidelines for primary stroke prevention for the management of asymptomatic carotid stenosis reflected evidences published before June 2007. After the publication of the first edition, several major clinical trials and observational studies have been published, and major guidelines updated their recommendation. Accordingly, the writing group of Korean Stroke Clinical Practice Guidelines (CPG) decided to provide timely updated evidence-based recommendations. The Korean Stroke CPG writing committee has searched and reviewed literatures related to the management of asymptomatic carotid stenosis including published guidelines, meta-analyses, randomized clinical trials, and nonrandomized studies published between June 2007 and Feb 2011. We summarized the new evidences and revised our recommendations. Key changes in the updated guidelines are the benefit of intensive medical therapy and further evidence of carotid artery stenting as an alternative to carotid endarterectomy. The current updated guidelines underwent extensive peer review by experts from the Korean Stroke Society, Korean Society of Intravascular Neurosurgery, Korean Society of Interventional Neuroradiology, Korean Society of Cerebrovascular Surgery, and Korean Neurological Association. New evidences will be continuously reflected in future updated guidelines.

Ischemic Stroke and Cancer: Stroke Severely Impacts Cancer Patients, While Cancer Increases the Number of Strokes

BACKGROUND: Cancer and ischemic stroke are two of the most common causes of death among the elderly, and associations between them have been reported. However, the main pathomechanisms of stroke in cancer patients are not well known, and can only be established based on accurate knowledge of the characteristics of cancer-related strokes. We review herein recent studies concerning the clinical, laboratory, and radiological features of patients with cancer-related stroke. MAIN CONTENTS: This review covers the epidemiology, underlying mechanisms, and acute and preventive treatments for cancer-related stroke. First, the characteristics of stroke (clinical and radiological features) and systemic cancer (type and extent) in patients with cancer-specific stroke are discussed. Second, the role of laboratory tests in the early identification of patients with cancer-specific stroke is discussed. Specifically, serum D-dimer levels (as a marker of a hypercoagulable state) and embolic signals on transcranial Doppler (suggestive of embolic origin) may provide clues regarding changes in the levels of coagulopathy related to cancer and anticoagulation. Finally, strategies for stroke treatment in cancer patients are discussed, emphasizing the importance of preventive strategies (i.e., the use of anticoagulants) over acute revascularization therapy in cancer-related stroke. CONCLUSION: Recent studies have revealed that the characteristics of cancer-related stroke are distinct from those of conventional stroke. Our understanding of the characteristics of cancer-related stroke is essential to the correct management of these patients. The studies presented in this review highlight the importance of a personalized approach in treating stroke patients with cancer.

Focused Update on Aspirin for Primary Stroke Prevention in Korean Clinical Practice Guidelines for Stroke

The first edition of the Korean clinical practice guidelines for primary stroke prevention reflects evidence published before June 2007. Since then, several clinical studies and meta-analyses have been conducted to determine the efficacy of aspirin for the primary prevention of cardiovascular disease including stroke. The aim of this guideline update is to provide timely recommendations taking into consideration the new evidence. Three clinical studies and four meta-analyses performed between July 2007 and November 2010 were identified and included for updating the guidelines. The main finding was a lack of aspirin efficacy for primary stroke prevention in patients with diabetes or peripheral arterial disease. We have summarized the new evidence and revised our recommendations for aspirin for primary stroke prevention. New evidence will need to be reflected continuously in future guideline updates.

Alternations of Septal-hippocampal System in the Adult Wistar Rat with Spatial Memory Impairments Induced by Chronic Cerebral Hypoperfusion

In the current investigation, the status of the septo-hippocampal cholinergic pathway and hippocampal mitogen-activated protein kinase (MAPK) signaling was examined in male Wistar rats with chronic cerebral hypoperfusion, which showed cognitive deficits based on assessment on a version of the Morris water maze. Chronic cerebral hypoperfusion was induced by bilateral common artery occlusion and maintained for 12 weeks until behavioral testing. Chronic cerebral hypoperfusion was shown to induce memory impairments and microglial activation in regions of white matter, including the fimbria of hippocampus. Choline acetyltransferase expression of the basal forebrain and expression of hippocampal MAPKs was decreased in rats with BCCAo compared to control rats. The results of this study suggest that cognitive decline induced by chronic cerebral hypoperfusion could be related to dysfunction of the basal forebrain cholinergic system and reduction of hippocampal MAPK activities.

The Factors Associated with the Decision of r-tPA Use in Acute Ischemic Stroke Patients Aged 80 Years or Older / 대한뇌졸중학회지

BACKGROUND: Small proportions of all the elderly stroke patients receive recombinant tissue plasminogen activator (r-tPA) therapy, although old age is not a proven contraindication to intravenous thrombolytic therapy for acute ischemic stroke. The purpose of this study was to identify reasons for exclusion from r-tPA therapy and factors associated with the decision of r-tPA use in elderly patients with acute ischemic stroke. METHODS: From the acute stroke registries of 22 domestic university hospitals taking the r-tPA therapy from January 2007 to May 2010, we extracted data of all acute ischemic stroke patients who were aged 80 or over and arrived within onset 3 hours. For all patients, we assessed the eligibility of r-tPA therapy using National Institute of Neurological Disorders and Stroke (NINDS) r-tPA trial criteria. For eligible patients, we compared all clinical variables between patients who were treated with r-tPA and those who were not, and analyzed potential factors related to the decision of r-tPA use. RESULTS: A total of 494 patients were included in this study. 255 patients (51.6%) were excluded by NINDS r-tPA trial criteria and the major reasons for exclusion were minor neurological deficit (53.7%) and clinical improvement (17.3%). Among 239 patients who were eligible for r-tPA, 162 (32.8%) patients received r-tPA and 77 (15.6%) did not. Multivariable analysis showed that younger age, shorter time-delay from onset to admission, non-smoker, no history of prior stroke, good pre-stroke functional status and severe initial neurological deficit were independently associated with the decision of r-tPA use in the elderly stroke patients predictors for r-tPA treatment. CONCLUSION: In very elderly patients, mild neurological deficit on arrival and rapid clinical improvement in neurological symptoms were the main reasons for exclusion from thrombolytic therapy.

Influence of Delirium on Functional Recovery in Acute Stroke

OBJECTIVE: To investigate the risk factors for poststroke delirium and evaluate its influence on functional recovery after ischemic stroke. METHOD: Risk factors for delirium were investigated retrospectively in three hundred twenty nine acute ischemic stroke patients over 60 years of age. Among the 329 patients, sixty seven developed delirium. Data were analyzed between delirium group (n=22) and control group (n=22) according to age, sex, lesion location and clinical features. Korean modified Barthel index (K-MBI), Korean National Institutes of Health stroke scale (K-NIHSS) and Korean mini-mental state examination (KMMSE) were measured at second and sixth weeks after onset and compared for both groups. RESULTS: Parameters showing statistically significant difference between two groups were age over 80, hyponatremia, sleep deprivation, cognitive impairment and cardiogenic embolism. There was no significant difference in K-MBI, K-NIHSS and K-MMSE scores at second week between the two groups. The delirium group showed significantly less improvement in K-MBI and K-NIHSS scores compared to control group (9.5+/-10.2 vs 18.5+/-11.6, p=0.011; -0.7+/-1.2 vs -1.8+/-1.3, p=0.014). There was no significant improvement in K-MMSE score. CONCLUSION: The possible risk factors for delirium in acute ischemic stroke are age over 80, hyponatremia, sleep deprivation, cognitive impairment and cardiogenic embolism. Stroke patients with comorbid delirium showed poorer functional outcome. Delirium seems to have detrimental effect in functional recovery after stroke.

Takotsubo Cardiomyopathy Following Cerebral Infarction Involving the Insular Cortex

BACKGROUND: Takotsubo cardiomyopathy is characterized by clinical features similar to those of acute myocardial ischemia, but without angiographic evidence of obstructive coronary artery disease. We present a patient with takotsubo cardiomyopathy following acute infarction involving the left insular cortex. CASE REPORT: A 52-year-old man was admitted with acute infarction of the left middle cerebral artery territory and acute chest pain. Acute myocardial infarction was suspected because of elevated serum troponin levels and hypokinesia of the left ventricle on echocardiography. However, a subsequent coronary angiography revealed no stenosis within the coronary arteries or ballooning of the apical left ventricle. CONCLUSIONS: We postulated that catecholamine imbalance due to the insular lesion could be responsible for these interesting features.