Woo-Keun Seo

Transcranial brain sonography in Parkinson's disease with restless legs syndrome

Substantia nigra (SN) hyperechogenicity assessed by transcranial brain sonography (TCS) is a characteristic finding in idiopathic Parkinsons disease (PD). In contrast, SN hypoechogenicity on TCS has been recently demonstrated in restless legs syndrome (RLS). RLS is one of the most common sleep problems in PD, but the pathophysiologic relationship between these two disorders has not been thoroughly elucidated. We compared the SN echogenicities of PD patients with and without RLS to investigate whether comorbid RLS in PD affects SN echogenicity and to explain the echogenic differences between idiopathic RLS (iRLS) and secondary PD–related RLS (pRLS). Sixty‐three PD patients (median age 64.6 ± 10.6 years), 40 iRLS patients (53.1 ± 11.7 years), and 40 healthy controls (69.1 ± 2.3 years) were enrolled in our study. All subjects answered a sleep questionnaire and underwent TCS. PD patients were subdivided into two groups, PD with RLS (PD+RLS, n = 26) and PD without RLS (PD‐RLS, n = 37), and the sonographic findings of each group were compared. Although significant hyperechogenicity was detected in both the SN and SN/midbrain ratios in both PD subgroups compared with the controls and the iRLS group (P < 0.001), there were no significant differences in SN echogenicity between the PD+RLS and PD‐RLS groups. Meanwhile, iRLS patients showed significant SN hypoechogenicity. In conclusion, comorbid RLS in PD did not have an impact on the sonographic SN findings. These results suggest that the pathogenesis of pRLS and iRLS involve different mechanisms. Further study will be required to clarify the association between RLS and PD.

Cerebral Microbleeds and Early Recurrent Stroke After Transient Ischemic Attack Results From the Korean Transient Ischemic Attack Expression Registry

IMPORTANCE The risk of early recurrent stroke after transient ischemic attack (TIA) may be modifiable by optimal treatment. Although ABCD2 scores, diffusion-weighted imaging lesions, and large artery stenosis are well known to predict early stroke recurrence, other neuroimaging parameters, such as cerebral microbleeds (CMBs), have not been well explored in patients with TIA. OBJECTIVE To determine the rate of early recurrent stroke after TIA and its neuroimaging predictors. DESIGN, SETTING, AND PARTICIPANTS In this hospital-based, multicenter prospective cohort study, consecutive patients with TIA were enrolled from 11 university hospitals from July 1, 2010, through December 31, 2012. Patients who were admitted within 24 hours after symptom onset and underwent diffusion-weighted imaging were included. MAIN OUTCOMES AND MEASURES The primary end point was recurrent stroke within 90 days. Baseline demographics, clinical manifestations, neuroimaging findings, and use of antithrombotics or statins also were analyzed. RESULTS A total of 500 patients (mean age, 64 years; male, 291 [58.2%]; median ABCD2 score, 4) completed 90-day follow-up with guideline-based management: antiplatelets (457 [91.4%]), anticoagulants (74 [14.8%]), and statins (345 [69.0%]). Recurrent stroke occurred in 25 patients (5.0%). Compared with patients without recurrent stroke, those with recurrent stroke were more likely to have crescendo TIA (20 [4.2%] vs 4 [16.0%], P = .03), white matter hyperintensities (146 [30.7%] vs 13 [52.0%], P = .03), and CMBs (36 [7.6%] vs 7 [28.0%], P = .003). On multivariable Cox proportional hazards analysis, CMBs remained as independent predictors for recurrent stroke (hazard ratio, 3.66; 95% CI, 1.47-9.09; P = .005). CONCLUSIONS AND RELEVANCE Immediate and optimal management seems to modify the risk of recurrent stroke after TIA. Cerebral microbleeds may be novel predictors of stroke recurrence, which needs further validation.

Carotid Intima-Media Thickness in Parkinson's Disease

There have been a few studies and inconsistent results regarding the coincidence of Parkinsons disease (PD) and atherosclerotic diseases, such as cerebrovascular disease. Carotid intima‐media thickness (IMT) is a known marker for subclinical atherosclerosis. The aim of this study was to investigate the carotid IMT between PD patients and controls. We studied 43 patients with PD and 86 matched controls. The carotid IMT in PD patients was significantly smaller than in controls (0.796 ± 0.179 mm vs. 0.913 ± 0.237 mm, P < 0.05). In multivariate analysis, the carotid IMT was inversely associated with the duration of levodopa medication and the severity of PD. These results suggest that PD patients have a lower risk of atherosclerosis.

Efficacy of early administration of escitalopram on depressive and emotional symptoms and neurological dysfunction after stroke: a multicentre, double-blind, randomised, placebo-controlled study.

BACKGROUND Mood and emotional disturbances are common in patients with stroke, and adversely affect the clinical outcome. We aimed to evaluate the efficacy of early administration of escitalopram to reduce moderate or severe depressive symptoms and improve emotional and neurological dysfunction in patients with stroke. METHODS This was a placebo controlled, double-blind trial done at 17 centres in South Korea. Patients who had had an acute stroke within the past 21 days were randomly assigned in a 1:1 ratio to receive oral escitalopram (10 mg/day) or placebo for 3 months. Randomisation was done with permuted blocks stratified by centre, via a web-based system. The primary endpoint was the frequency of moderate or severe depressive symptoms (Montgomery-Åsberg Depression Rating Scale [MADRS] ≥16). Endpoints were assessed at 3 months after randomisation in the full analysis set (patients who took study medication and underwent assessment of primary endpoint after randomisation), in all patients who were enrolled and randomly assigned (intention to treat), and in all patients who completed the trial (per-protocol analysis). This trial is registered with ClinicalTrials.gov, number NCT01278498. FINDINGS Between Jan 27, 2011, and June 30, 2014, 478 patients were assigned to placebo (n=237) or escitalopram (n=241); 405 were included in the full analysis set (195 in the placebo group, 210 in the escitalopram group). The primary outcome did not differ by study group in the full analysis set (25 [13%] patients in the placebo group vs 27 [13%] in the escitalopram group; odds ratio [OR] 1·00, 95% CI 0·56-1·80; p>0·99) or in the intention-to-treat analysis (34 [14%] vs 35 [15%]; OR 1·01, 95% CI 0·61-1·69, p=0·96). The study medication was generally well tolerated; the most common adverse events were constipation (14 [6%] patients who received placebo vs 14 [6%] who received escitalopram), muscle pain (16 [7%] vs ten [4%]), and insomnia (12 [5%] vs 12 [5%]). Diarrhoea was more common in the escitalopram group (nine [4%] patients) than in the placebo group (two [1%] patients). INTERPRETATION Escitalopram did not significantly reduce moderate or severe depressive symptoms in patients with acute stroke. FUNDING Dong-A Pharmaceutical and Ministry for Health, Welfare, and Family Affairs, South Korea.

Elevated free fatty acid is associated with cardioembolic stroke subtype.

BACKGROUND AND OBJECTIVES Free fatty acids (FFAs), an important energy substrate, have an association with cardiovascular diseases, such as atherosclerosis, myocardial dysfunction and abnormal cardiac rhythm. However, limited reports are available on the association between FFAs and ischemic stroke. We hypothesized that plasma FFA concentration could be associated with an ischemic stroke, emphasizing the relationship between FFA and subtypes of ischemic stroke. METHODS A cross-sectional study examined the association between FFA concentration and subtypes of stroke and cerebral atherosclerosis from a hospital-based acute stroke registry. RESULTS Data of 715 stroke patients were analyzed. The concentration of FFA was highest in the cardioembolic stroke subtype compared with the other stroke subtypes. Logistic regression analysis revealed that an increase in FFA concentration was significantly associated with the cardioembolic subtype after the adjustment of covariates. FFA concentration was also higher in patients with atrial fibrillation (AF) than those without AF. According to the presence of atherosclerotic stenosis, no significantly difference of FFA concentration was found for intracranial and extracranial cerebral arterial atherosclerosis. CONCLUSION Here we report a significant association between fasting FFA concentration and the cardioembolic stroke subtype. AF is suggested as the mediating factor between FFA and the cardioembolic stroke subtype.

Lack of association between antisperm antibodies and language dysfunction in Alzheimer's disease

Alzheimers disease (AD) is the single most common cause of primary dementia. Language-based frontotemporal dementia, another type of primary dementia, is known as primary progressive aphasia (PPA). Although the cardinal feature of AD is a progressive loss of memory, many patients with AD also present with language impairment. Moreover AD and PPA have partially shared pathophysiology. Recently, it was suggested that a history of vasectomy might be a risk factor for PPA, by immune responses to sperm or antisperm antibody (ASA), which has long been known to have antigenic property. As ASAs could develop naturally in both men and women, we studied the relation between the presence of ASAs and cognitive function in AD. A total of 86 elderly were selected (46 patient with AD, 20 with mild cognitive impairment, and 20 without cognitive dysfunction) and were assessed for the presence of ASAs with neuropsychological evaluation. However, there were no significant differences in the distribution of ASAs according to cognitive status or language function status. Thus, the current study does not support the association between the immune responses and language dysfunction in AD.

Rivaroxaban vs Warfarin Sodium in the Ultra-Early Period After Atrial Fibrillation–Related Mild Ischemic Stroke: A Randomized Clinical Trial

Importance In atrial fibrillation (AF)–related acute ischemic stroke, the optimal oral anticoagulation strategy remains unclear. Objective To test whether rivaroxaban or warfarin sodium is safer and more effective for preventing early recurrent stroke in patients with AF-related acute ischemic stroke. Design, Setting, and Participants A randomized, multicenter, open-label, blinded end point evaluation, comparative phase 2 trial was conducted from April 28, 2014, to December 7, 2015, at 14 academic medical centers in South Korea among patients with mild AF-related stroke within the previous 5 days who were deemed suitable for early anticoagulation. Analysis was performed on a modified intent-to-treat basis. Interventions Participants were randomized 1:1 to receive rivaroxaban, 10 mg/d for 5 days followed by 15 or 20 mg/d, or warfarin with a target international normalized ratio of 2.0-3.0, for 4 weeks. Main Outcomes and Measures The primary end point was the composite of new ischemic lesion or new intracranial hemorrhage seen on results of magnetic resonance imaging at 4 weeks. Primary analysis was performed in patients who received at least 1 dose of study medications and completed follow-up magnetic resonance imaging. Key secondary end points were individual components of the primary end point and hospitalization length. Results Of 195 patients randomized, 183 individuals (76 women and 107 men; mean [SD] age, 70.4 [10.4] years) completed magnetic resonance imaging follow-up and were included in the primary end point analysis. The rivaroxaban group (n = 95) and warfarin group (n = 88) showed no differences in the primary end point (47 [49.5%] vs 48 [54.5%]; relative risk, 0.91; 95% CI, 0.69-1.20; P = .49) or its individual components (new ischemic lesion: 28 [29.5%] vs 31 of 87 [35.6%]; relative risk, 0.83; 95% CI, 0.54-1.26; P = .38; new intracranial hemorrhage: 30 [31.6%] vs 25 of 87 [28.7%]; relative risk, 1.10; 95% CI, 0.70-1.71; P = .68). Each group had 1 clinical ischemic stroke, and all new intracranial hemorrhages were asymptomatic hemorrhagic transformations. Hospitalization length was reduced with rivaroxaban compared with warfarin (median, 4.0 days [interquartile range, 2.0-6.0 days] vs 6.0 days [interquartile range, 4.0-8.0]; P < .001). Conclusions and Relevance In mild AF-related acute ischemic stroke, rivaroxaban and warfarin had comparable safety and efficacy. Trial Registration clinicaltrials.gov Identifier: NCT02042534

Arterial Dissection as a Cause of Intracranial Stenosis in East Asians

Intracranial steno-occlusive disease is a common cause of stroke worldwide and is more prevalent in Asians. We hypothesized that nontraumatic intracranial artery dissection (ICAD) is a common hidden cause of large intracranial steno-occlusive disease in Asian patients with ischemic stroke and that

Protocol for the comparison of triflusal and clopidogrel in secondary prevention of stroke based on cytochrome P450 2C19 genotyping (MASETRO study): A multicenter, randomized, open-label, parallel-group trial

Rationale and aim The antiplatelet effect of clopidogrel is reportedly influenced by cytochrome P450 2C19 (CYP2C19) polymorphisms. However, there is no data concerning the relationship between stroke recurrence and CYP2C19 polymorphisms in patients treated with clopidogrel for secondary prevention of ischemic stroke. Triflusal may be an alternative therapy for clopidogrel in patients with poor genotype. The Comparison of Triflusal and Clopidogrel Effects in Secondary Prevention of Stroke Based on Cytochrome P450 2C19 Genotyping (MAESTRO) study will investigate the effect of antiplatelet agents based on CYP2C19 polymorphisms in secondary prevention of ischemic stroke. Sample size and design Assuming that 55% of patients belong to the poor genotype group, the required sample size is 1080 patients with at least 24 months of follow-up. This study is designed as a prospective, multicenter, randomized, parallel-group, open-label, and blind genotype trial. Patients who experience their first non-cardiogenic ischemic stroke within 30 days prior to screening are eligible. Patients received 300 mg triflusal twice a day or 75 mg clopidogrel once daily during the trial. The study is registered with ClinicalTrials.gov (NCT01174693). Study outcome The primary outcome is recurrent ischemic stroke or hemorrhagic stroke. Secondary outcomes consist of composite major vascular events including stroke, myocardial infarction, coronary revascularization, or vascular death. Discussion Personalized medicine may be essential for patients according to individual drug metabolism abilities. MAESTRO is the first prospective study designed to evaluate the effect of CYP2C19 polymorphism in secondary stroke prevention and will resolve several questions regarding preventive antiplatelet agents for recurrent stroke.

Generalized Chorea Induced by an Unilateral Anterior Cerebral Artery Territorial Infarction

Generalized chorea caused by unilateral cerebral infarction has rarely been reported. A 58-year-old woman presented involuntary movement in her all extremities after acute cerebral infarction on her right anterior cerebral artery territory. The involuntary movements were diagnosed as generalized chorea. We didn’t find any cause of generalized chorea except the acute cerebral infarction. Here, we described the case of generalized chorea after unilateral cerebral infarction discussing the possible mechanisms.