Effectiveness of the 10 cm2 Rivastigmine Patch in Taiwanese Patients with Mild-to-Moderate Alzheimer's Dementia: A 48-Week Real-World Observational Study.

INTRODUCTION: The current study aimed to provide data on the effectiveness of the 10 cm2 rivastigmine patch in patients with Alzheimer's disease (AD) in a real-world setting in Taiwan. METHODS: This was a 48-week, single-arm, open-label, observational, and post-marketing study conducted across seven centers in Taiwan between May 5, 2016 and July 10, 2017. Eligible patients (aged 55-95 years) treated with the 10 cm2rivastigmine patch were enrolled based on physicians' judgment and according to the Taiwan reimbursement criteria of the drug. Data were prospectively collected at Week 0 (baseline), Week 24, and Week 48. The primary endpoint was the change in the cognitive assessment screening instrument (CASI) scores at Week 48 versus baseline. The changes from baseline in clinical dementia rating (CDR), mini-mental state examination (MMSE), and neuropsychiatric inventory (NPI) scores were evaluated, as were treatment persistence and the safety profile. RESULTS: Of the 285 eligible patients [full analysis set (FAS)], 216 (75.8%) completed the study protocol while 180 (63.2%) persisted on the 10 cm2 rivastigmine patch for the full 48 weeks. At baseline, 89.8% of patients had a CDR score of 0.5 or 1, while the change in CDR score at Week 48 was not significant. In the FAS, both the CASI and MMSE scores had numerical improvement at Week 24 but declined by 2.1 and 0.4 points, respectively, at Week 48 (p = 0.005 and p = 0.022). The increment in NPI scores was not significant. The most common drug-related adverse events (AEs) were pruritus (11.2%), nausea (3.5%), rash (3.2%), and vomiting (2.8%). CONCLUSIONS: The use of the 10 cm2 rivastigmine patch in the mild stage of AD maintained cognitive function at Week 24 and neuropsychiatric function at Week 48. The treatment persistency and safety profile support the clinical tolerability of the rivastigmine patch in the management of mild-to-moderate AD in Taiwan.

HDAC inhibitor protects chronic cerebral hypoperfusion and oxygen-glucose deprivation injuries via H3K14 and H4K5 acetylation-mediated BDNF expression.

Vascular dementia (VaD) is the second most common cause of dementia, but the treatment is still lacking. Although many studies have reported that histone deacetylase inhibitors (HDACis) confer protective effects against ischemic and hypoxic injuries, their role in VaD is still uncertain. Previous studies shown, one HDACi protected against cognitive decline in animals with chronic cerebral hypoperfusion (CCH). However, the underlying mechanisms remain elusive. In this study, we tested several 10,11-dihydro-5H-dibenzo[b,f]azepine hydroxamates, which act as HDACis in the CCH model (in vivo), and SH-SY5Y (neuroblastoma cells) with oxygen-glucose deprivation (OGD, in vitro). We identified a compound 13, which exhibited the best cell viability under OGD. The compound 13 could increase, in part, the protein levels of brain-derived neurotrophic factor (BDNF). It increased acetylation status on lysine 14 residue of histone 3 (H3K14) and lysine 5 of histone 4 (H4K5). We further clarified which promoters (I, II, III, IV or IX) could be affected by histone acetylation altered by compound 13. The results of chromatin immunoprecipitation and Q-PCR analysis indicate that an increase in H3K14 acetylation leads to an increase in the expression of BDNF promoter II, while an increase in H4K5 acetylation results in an increase in the activity of BDNF promoter II and III. Afterwards, these cause an increase in the expression of BDNF exon II, III and coding exon IX. In summary, the HDACi compound 13 may increase BDNF specific isoforms expression to rescue the ischemic and hypoxic injuries through changes of acetylation on histones.

Cost-effectiveness of statin therapy for secondary prevention among patients with coronary artery disease and baseline LDL-C 70-100 mg/dL in Taiwan.

BACKGROUND: The recommended target low-density lipoprotein cholesterol (LDL-C) level for coronary artery disease (CAD) patients has been lowered from 100 to 70 mg/dL in several clinical guidelines for secondary prevention. We aimed to assess whether initiating statin treatment in CAD patients with baseline LDL-C 70-100 mg/dL in Taiwan could be cost-effective. METHODS: A Markov model was developed to simulate a hypothetical cohort of CAD patients with a baseline LDL-C level of 90 mg/dL. The incidence and recurrence of MI and stroke related to specific LDL-C levels as well as the statin effect, mortality rate, and health state utilities were obtained from the literature. The direct medical costs and rate of fatal events were derived from the national claims database. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) was calculated, and sensitivity analyses were performed. RESULTS: Moderate-intensity statin use, a treatment regimen expected to achieve LDL <70 mg/dL in the base case, resulted in a net gain of 562 QALYs but with an additional expenditure of $11.4 million per 10,000 patients over ten years. The ICER was $20,288 per QALY gained. The probabilities of being cost-effective at willingness-to-pay thresholds of one and three gross domestic product per capita ($24,329 in 2017) per QALY were 51.1% and 94.2%, respectively. Annual drug cost was the most influential factor on the ICER. CONCLUSION: Lowering the target LDL-C level from 100 to 70 mg/dL among treatment-naïve CAD patients could be cost-effective given the health benefits of preventing cardiovascular events and deaths.

Serum lipid level is not associated with symptomatic intracerebral hemorrhage after intravenous thrombolysis for acute ischemic stroke.

BACKGROUND: This study assessed whether serum lipid levels are associated with the risk of symptomatic intracerebral hemorrhage (sICH) and functional outcomes in patients with acute ischemic stroke after receiving intravenous thrombolysis. METHODS: We retrospectively analyzed consecutive ischemic stroke patients who were treated with intravenous tissue plasminogen activator between January 2007 and January 2017. Lipid levels on admission, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels, as well as potential predictors of sICH were tested using univariate and multivariate analyses. RESULTS: Of the 229 enrolled patients (100 women, aged 68 ± 13 years), 14 developed sICH and 103 (45%) had favorable functional outcomes at 3 months. The patients with sICH more often had diabetes mellitus (71% vs. 26%, P = 0.01) and had more severe stroke (mean National Institutes of Health Stroke Scale [NIHSS] score of 16 vs. 13, P = 0.045). Regarding lipid subtype, total cholesterol, LDL-C, HDL-C, and triglyceride levels were not associated with sICH or functional outcomes. According to the results of multivariate analysis, the frequency of sICH was independently associated with diabetes mellitus (odds ratio [OR] = 6.04; 95% CI [1.31-27.95]; P = 0.02) and the NIHSS score (OR = 1.12; 95% CI [1.02-1.22]; P = 0.01). A higher NIHSS score was independently associated with unfavorable functional outcomes (OR = 0.86; 95% CI [0.81-0.91]; P < 0.001). CONCLUSIONS: Serum lipid levels on admission, including total cholesterol, LDL-C, HDL-C, and triglyceride levels, were not associated with sICH or 3-month functional outcomes after intravenous thrombolysis for acute ischemic stroke.

Predicting functional outcomes of posterior circulation acute ischemic stroke in first 36 h of stroke onset.

Posterior circulation acute ischemic stroke constitutes one-fourth of all ischemic strokes and can be efficiently quantified using the posterior circulation Alberta stroke program early computed tomography score (PC-ASPECTS) through diffusion-weighted imaging. We investigated whether the PC-ASPECTS and National Institutes of Health Stroke Scale (NIHSS) facilitate functional outcome prediction among Chinese patients with posterior circulation acute ischemic stroke. Participants were selected from our prospective stroke registry from January 1, 2015, to December 31, 2016. The baseline NIHSS score was assessed on the first day of admission, and brain magnetic resonance imaging was performed within 36 h after stroke onset. Simple and multiple logistic regressions were conducted to determine stroke risk factors and the PC-ASPECTS. Receiver operating characteristics (ROC) curve analysis was performed to compare the NIHSS and PC-ASPECTS. Of 549 patients from our prospective stroke admission registry database, 125 (22.8%) had a diagnosis of posterior circulation acute ischemic stroke. The optimal cutoff for the PC-ASPECTS in predicting outcomes was 7. The odds ratios of the PC-ASPECTS (≤ 7 vs > 7) in predicting outcomes were 6.33 (p = 0.0002) and 8.49 (p = 0.0060) in the univariate and multivariate models, respectively, and 7.52 (p = 0.0041) in the aging group. On ROC curve analysis, the PC-ASPECTS demonstrated more reliability than the baseline NIHSS for predicting functional outcomes of minor posterior circulation stroke. In conclusion, both the PC-ASPECTS and NIHSS help clinicians predict functional outcomes. PC-ASPECTS > 7 is a helpful discriminator for achieving favorable functional outcome prediction in posterior circulation acute ischemic stroke.

Impact of MCA stenosis on the early outcome in acute ischemic stroke patients.

BACKGROUND: Asians have higher frequency of intracranial arterial stenosis. The present study aimed to compare the clinical features and outcomes of ischemic stroke patients with and without middle cerebral artery (MCA) stenosis, assessed by transcranial sonography (TCS), based on the Taiwan Stroke Registry (TSR). METHODS: Patients with acute ischemic stroke or transient ischemic attack registered in the TSR, and received both carotid duplex and TCS assessment were categorized into those with stenosis (≥50%) and without (<50%) in the extracranial internal carotid artery (ICA) and MCA, respectively. Logistic regression analysis, Kaplan-Meier method and Cox proportional hazard model were applied to assess relevant variables between groups. RESULTS: Of 6003 patients, 23.3% had MCA stenosis, 10.1% ICA stenosis, and 3.9% both MCA and ICA stenosis. Patients with MCA stenosis had greater initial NIHSS, higher likelihood of stroke-in-evolution, and more severe disability than those without (all p<0.001). Patients with MCA stenosis had higher prevalence of hypertension, diabetes and hypercholesterolemia. Patients with combined MCA and extracranial ICA stenosis had even higher NIHSS, worse functional outcome, higher risk of stroke recurrence or death (hazard ratio, 2.204; 95% confidence intervals, 1.440-3.374; p<0.001) at 3 months after stroke than those without MCA stenosis. CONCLUSIONS: In conclusion, MCA stenosis was more prevalent than extracranial ICA stenosis in ischemic stroke patients in Taiwan. Patients with MCA stenosis, especially combined extracranial ICA stenosis, had more severe neurological deficit and worse outcome.

Comparison of admission random glucose, fasting glucose, and glycated hemoglobin in predicting the neurological outcome of acute ischemic stroke: a retrospective study.

BACKGROUND: Hyperglycemia is a known predictor of negative outcomes in stroke. Several glycemic measures, including admission random glucose, fasting glucose, and glycated hemoglobin (HbA1c), have been associated with bad neurological outcomes in acute ischemic stroke, particularly in nondiabetic patients. However, the predictive power of these glycemic measures is yet to be investigated. METHODS: This retrospective study enrolled 484 patients with acute ischemic stroke from January 2009 to March 2013, and complete records of initial stroke severity, neurological outcomes at three months, and glycemic measures were evaluated. We examined the predictive power of admission random glucose, fasting glucose, and HbA1c for neurological outcomes in acute ischemic stroke. Furthermore, subgroup analyses of nondiabetic patients and patients with diabetes were performed separately. RESULTS: Receiver operating characteristic (ROC) analysis revealed that admission random glucose and fasting glucose were significant predictors of poor neurological outcomes, whereas HbA1c was not (areas under the ROC curve (AUCs): admission random glucose = 0.564, p = 0.026; fasting glucose = 0.598, p = 0.001; HbA1c = 0.510, p = 0.742). Subgroup analyses of nondiabetic patients and those with diabetes revealed that only fasting glucose predicts neurological outcomes in patients with diabetes, and the AUCs of these three glycemic measures did not differ between the two groups. A multivariate logistic regression analysis of the study patients indicated that only age, initial stroke severity, and fasting glucose were independent predictors of poor neurological outcomes, whereas admission random glucose and HbA1c were not (adjusted odds ratio: admission random glucose = 1.002, p = 0.228; fasting glucose = 1.005, p = 0.039; HbA1c = 1.160, p = 0.076). Furthermore, subgroup multivariate logistic regression analyses of nondiabetic patients and those with diabetes indicated that none of the three glycemic measures were associated with poor neurological outcomes. DISCUSSION: Fasting glucose is an independent predictor of poor neurological outcomes in patients with acute ischemic stroke and had greater predictive power than that of admission random glucose and HbA1c. The predictive power of glycemic measures for poor neurological outcomes did not differ significantly between the nondiabetic patients and those with diabetes.

Time-Varying Effects of Psychological Distress on the Functional Recovery of Stroke Patients.

OBJECTIVE: To explore the temporal effects of psychological distress on the functional recovery of stroke survivors. DESIGN: A longitudinal follow-up study. All participants were interviewed at 5 days after stroke onset, and at 1, 2, 3, and 6 months after discharge from acute care hospitals. SETTING: Neurology inpatient and outpatient departments and rehabilitation clinics. PARTICIPANTS: First-time stroke participants (N=62) without cognitive impairment, psychiatric disorders, or cancer were recruited. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Measurements consisted of demographic characteristics, disease severity, social support, the Chinese version of the Emotional and Social Dysfunction Questionnaire (ESDQ_C), and the Barthel Index. RESULTS: Our findings showed that psychological distress had a dynamic effect on functional recovery over time, and as the total ESDQ_C score increased by 1 point, the concurrent functional recovery decreased by .23 points (P<.001). Additionally, 5 subscales of the ESDQ_C including anger, emotional dyscontrol, helplessness, indifference, and euphoria also had dynamic effects on functional recovery over time (P<.05). Regardless of when a single form or various forms of psychological distress occurred over time from stroke onset, the functional recovery over time was simultaneously affected. CONCLUSIONS: The time-varying effect of psychological distress on functional recovery was significant. Adopting comprehensive instruments and regular assessments for the early detection of various psychological distresses while under clinical care is needed. Effective interventions targeting both physical and mental functions would further improve the functional recovery and overall health of stroke patients.

Predicting Mortality in Patients With "Malignant" Middle Cerebral Artery Infarction Using Susceptibility-Weighted Magnetic Resonance Imaging: Preliminary Findings.

To evaluate malignant middle cerebral artery (MCA) infarction (defined as space-occupying edema in more than 50% to 75% of the MCA territory) on magnetic resonance imaging (MRI) with susceptibility-weighted imaging (SWI) sequence and assess the usefulness of SWI findings, diffusion-weighted imaging (DWI) findings, and apparent diffusion coefficient (ADC) as predictors of clinical outcome.Data from 16 patients with large MCA infarction previously admitted to our institution between December 2009 and October 2012 were retrospectively collected and analyzed. Within 7 days after stroke onset, 1 neurologist and 1 neuroradiologist estimated the area of infarction on DWI/ADC and extent of prominent vessel sign (PVS) on SWI images using the Stroke Program Early MR Score (SPEMRS). The PVS on SWI was defined as a local prominence of hypointense vessels with either increased vessel number or diameter in the target area, when compared with the number or diameter of the contralateral MCA territory vessels.Six patients died and 10 survived. Although the DWI/ADC-SPEMRS and clinical profiles were similar between the nonsurvivor and survivor groups, SWI-SPEMRS was significantly lower in the nonsurvivor group (P < 0.001).The area of deoxygenation on SWI in patients with malignant MCA infarction can predict mortality. Lower SWI-SPEMRS is a potentially better predictor of poor outcome than lower DWI-SPEMRS. A larger prospective study is needed to clarify the role of SWI as a therapeutic guide in malignant MCA.

Prominent vessel sign on susceptibility-weighted imaging in acute stroke: prediction of infarct growth and clinical outcome.

BACKGROUND AND PURPOSE: Predicting the risk of further infarct growth in stroke patients is critical to therapeutic decision making. We aimed to predict early infarct growth and clinical outcome from prominent vessel sign (PVS) identified on the first susceptibility-weighted image (SWI) after acute stroke. MATERIALS AND METHODS: Twenty-two patients with middle cerebral artery (MCA) infarction had diffusion-weighted imaging, SWI, MR angiography, and clinical evaluation using the National Institutes of Health Stroke Scale at 7-60 hours and 5-14 days after stroke onset. Late-stage clinical evaluation at 1 and 3 months used the modified Rankin Scale. The infarct area and growth were scored from 10 (none) to 0 (infarct or growth in all 10 zones) using the Alberta Stroke Program Early CT Score (ASPECTS) system. RESULTS: Infarct growth on the second MRI occurred in 13 of 15 patients with PVS on the first MRI and not in any patient without PVS (n=7; r=0.86, P<0.001). The extent of PVS was significantly correlated with infarct growth (r=0.82, P<0.001) and early-stage outcome (P=0.02). No between-group difference in late-stage clinical outcome was found. CONCLUSION: PVS on the first SWI after acute MCA territory stroke is a useful predictor of early infarct growth. Extensive PVS within the large MCA territory is related to poor early-stage outcome and could be useful for clinical assessment of stroke.

Adiponectin and leptin in overweight/obese and lean women with polycystic ovary syndrome.

AIM: The objective of this study was to evaluate the adiponectin and leptin levels in overweight/obese and lean women with polycystic ovary syndrome (PCOS). DESIGN: This was a retrospective study. PATIENTS: Of the 422 studied patients, 224 women with PCOS and 198 women without PCOS were evaluated. MAIN OUTCOME MEASURE(S): Insulin resistance and the metabolic components were assessed. The adiponectin and leptin levels were also evaluated. RESULTS: Adiponectin was negatively correlated with insulin resistance, body mass index (BMI), and total testosterone, triglyceride, and low-density lipoprotein (LDL) levels; conversely, leptin reversed the aforementioned reaction and was negatively correlated with adiponectin levels. The adiponectin to leptin ratios were significantly lower in PCOS women than in those without PCOS. Compared to women with non-PCOS, overweight/obese women with PCOS had lower serum adiponectin levels than women without PCOS, which was not the case for lean women. Conversely, lean women with PCOS had higher serum leptin levels than those without PCOS, which was not the case for overweight/obese women. CONCLUSIONS: Adipose tissue might play an important role in the metabolic complications in women with PCOS. To study the impact of obesity biomarkers in women with PCOS, overweight/obese and lean women should be considered separately.

Bilateral Paramedian Thalamic Infarction Presenting as Status Epilepticus: A Case Report and Review of the Literatures.

PURPOSE: Occlusion of the artery of Percheron (AOP), a rare vascular variant of basilar artery branch, is presumed to cause bilateral paramedian thalamic infarction. We present a case of acute AOP infarction with status epilepticus. CASE REPORT: A 65-year-old woman had past history of hypertension, type 2 diabetes mellitus, and major depressive disorder. She was found to have altered mental status on awakening. She developed tonic convulsion and progressed to status epilepticus later. The brain magnetic resonance imaging (MRI) showed acute bilateral paramedian thalamic and interpeduncular mesencephalic infarction. The electroencephalography (EEG) showed continuous epileptiform discharges. After receiving antiplatelet and anticonvulsant agents, she regained her level of consciousness and has completely recovered to previous baseline. CONCLUSIONS: To our knowledge, this is the first case of AOP infarction presenting status epilepticus. Early recognition and treatment of seizure may reverse altered mental status in those patients.

Stroke after burn: population data analysis.

PURPOSE OF THE STUDY: We aimed to describe a population cohort study of burns with the prevalence of stroke, and discuss possible etiologies. ANALYTICAL METHODS: This study uses data obtained from the Longitudinal Health Insurance Database 2005 (LHID2005). The study cohort consisted of all patients who had diagnoses of burn recorded in the database (ICD-9-CM codes 948) between January 1 2004 and December 31 2008 (N=1549). MAIN FINDINGS: The patients with burn and the comparison cohort are 7410 patients, 146 experienced stroke during the follow-up period of up to 5 years. In average, the burn patients suffered from stroke by 1.48 years after burn. The hazard ratio of stroke was 1.74 (95% CI, 1.15-2.63) for patients with TBSA burn <20%, 3.78 (95% CI, 1.39-10.26) for patients with TBSA burn ≥20%. The adjusted hazard ratio of ischemic stroke was 1.63 for patients with TBSA burn <20%, 2.96 for patients with TBSA burn ≥20%, whereas the hazard ratio of hemorrhagic stroke were not significant (p=0.231). CONCLUSIONS: In our study, severe burned patients, more than 60 years of age, had higher risk of stroke in their recovery life. We suggest close follow up for the burn patients in high risk of stroke.

CHA2DS2-VASc Score and Heart Rate Predict Ischemic Stroke Outcomes in Patients withAtrial Fibrillation.

PURPOSE: To evaluate the factors determining the severity and outcome of ischemic stroke in patients with atrial fibrillation (AF). METHODS: Our study examined 210 patients with AF and acute ischemic stroke to investigate the relative risks of age, gender, comorbidities, CHADS2 and CHA2DS2-VASc scores, warfarin use, heart rate, and blood pressure on stroke severity, hospitalization duration, and mortality rate. RESULTS: Patients with poor outcomes [n = 109, National Institutes of Health Stroke Scale (NIHSS) scores of ≥ 8] had elevated CHA2DS2-VASc scores [5, interquartile range (IQR) 3-6 versus 4, IQR 2.5-5, p = 0.005] and were older with a female predominance, less prior warfarin use, and a higher heart rate (93 ± 24 versus 84 ± 20 beats/min, p = 0.004) in the emergency department, with a longer duration of hospitalization (24 ± 23 versus 11 ± 12 days, p < 0.001) and a higher mortality rate (11.0% versus 0.0%, p = 0.002) than those with better outcomes (n = 101, low NIHSS scores of ≤ 7). Patients who died (n = 12) were older and had a higher NIHSS, CHADS2 (3.5, IQR 2-4.75 versus 2, IQR 1-4, p = 0.040), or CHA2DS2-VASc (5.5, IQR 4-6 versus 4, IQR 3-5, p = 0.046) scores than patients who survived. The multivariate analysis showed that female gender, no prior warfarin use, and heart rate were independent predictors of stroke severity. CONCLUSIONS: Our results showed that CHADS2 and CHA2DS2-VASc scores, and heart rate were useful parameters for predicting outcomes in AF patients with stroke. KEY WORDS: Atrial fibrillation; CHA2DS2-VASc score; Heart rate; Ischemic stroke.

Pathogen colonization in patients with acute cerebral stroke.

PURPOSE: To identify the pathogens that frequently cause infection and to explore their clinical features in acute stroke patients. METHODS: From June 1, 1999 to December 31, 2008, we reviewed medical records of 263 patients with acute stroke and 351 controls. Within 30 days from admission, 109 and 107 patients had one or more bacterial cultures, respectively. The cumulative bacteria-free probability of all patients and the incidence of each isolated pathogen were assessed. We searched for the factors associated with isolation of different Gram-negative bacilli (GNB). RESULTS: Patients with recent stroke were prone to healthcare-associated colonization within 2 weeks from admission. One-fourth of stroke patients had positive bacterial culture. Stroke patients had a high incidence of Staphylococcus aureus and various GNB in their sputum. When urinary tract infections (UTIs) began 9 days or more after admission, the contributory pathogens were most often glucose-nonfermenting bacilli. However, if UTIs occurred within 9 days after admission, the pathogens were likely to be Enterobacteriaceae bacilli. CONCLUSIONS: Stroke patients had high incidence of pathogenic bacteria in their sputum which might be prone to pneumonia. The time after admission of the onset of UTI is useful information for predicting contributory pathogens and planning for appropriate treatment.

The relationship between carotid intima-media thickness and endogenous androgens in young women with polycystic ovary syndrome in Taiwan.

Polycystic ovary syndrome (PCOS) is a common and complex female endocrinopathy that is associated with multiple vascular risk factors. Our objective was to investigate the relationship between carotid intima-media thickness (CIMT) and endogenous androgens in young Taiwanese-Chinese women with PCOS. We measured CIMT with B-mode ultrasound in 42 young PCOS patients and 43 controls. Atherosclerosis-associated profiles and endocrinological parameters were also measured. The results showed that although Taiwanese-Chinese PCOS patients tend to possess more risk factors for atherosclerosis than controls, there was no evidence to support that they have a greater CIMT at this age. Furthermore, androstenedione appears to be inversely associated with CIMT.

Epistasis analysis for estrogen metabolic and signaling pathway genes on young ischemic stroke patients.

BACKGROUND: Endogenous estrogens play an important role in the overall cardiocirculatory system. However, there are no studies exploring the hormone metabolism and signaling pathway genes together on ischemic stroke, including sulfotransferase family 1E (SULT1E1), catechol-O-methyl-transferase (COMT), and estrogen receptor α (ESR1). METHODS: A case-control study was conducted on 305 young ischemic stroke subjects aged

Association between genetic variant on chromosome 12p13 and stroke survival and recurrence: a one year prospective study in Taiwan.

BACKGROUND: The association between ischemic stroke and 2 single nucleotide polymorphisms (SNPs) on chromosome 12p13, rs12425791 and rs11833579 appears inconsistent across different samples. These SNPs are close to the ninjurin2 gene which may alter the risk of stroke by affecting brain response to ischemic injury. The purpose of this study was to investigate the association between these two SNPs and ischemic stroke risk, as well as prognostic outcomes in a Taiwanese sample. METHODS: We examined the relations of these two SNPs to the odds of new-onset ischemic stroke, ischemic stroke subtypes, and to the one year risk of stroke-related death or recurrent stroke following initial stroke in a case-control study. A total of 765 consecutive patients who had first-ever ischemic stroke were compared to 977 stroke-free, age-matched controls. SNPs were genotyped by Taqman fluorescent allelic discrimination assay. The association between ischemic stroke and SNPs were analyzed by multivariate logistic regression. Cox proportional hazard model was used to assess the effect of individual SNPs on stroke-related mortality or recurrent stroke. RESULTS: There was no significant association between SNP rs12425791 and rs11833579 and ischemic stroke after multiple testing corrections. However, the marginal significant association was observed between SNP rs12425791 and large artery atherosclerosis under recessive model (OR, 2.30; 95%CI, 1.22-4.34; q-value = 0.062). Among the 765 ischemic stroke patients, 59 died or developed a recurrent stroke. After adjustment for age, sex, vascular risk factors and baseline stroke severity, Cox proportional hazard analysis indicated that the hazard ratios were 2.76 (95%CI, 1.34-5.68; q-value, 0.02) and 2.15 (95%CI, 1.15-4.02; q-value, 0.03) for individuals with homozygous variant allele of rs12425791 and rs11833579, respectively. CONCLUSIONS: This is a precedent study that found genetic variants of rs12425791 and rs11833579 on chromosome 12p13 are independent predictors of stroke-related mortality or stroke recurrence in patients with incident ischemic stroke in Taiwan. Further study is needed to explore the details of the physiological function and the molecular mechanisms underlying the association of this genetic locus with ischemic stroke.

An old lady with anterior chest pain and unilateral facial flushing.

Harlequin syndrome is rare and typically characterized by asymmetric flushing and sweating. Although it is usually considered idiopathic, literature review shows that it may be caused by lesion over lung apex or after central venous catheterization in the internal jugular vein. We present a 74-year-old woman who had been experiencing recurrent chest pain and right shoulder pain since 2 weeks ago. The tentative diagnosis was made by the emergency physician (EP) as acute coronary syndrome. The patient was given nitroglycerin treatment. Twelve hours later, the patient developed another episode of chest pain. The electrocardiogram and cardiac enzyme study results were, however, both normal. Further evaluation showed intermittent flushing over the left side of her face, as well as right-eye ptosis. A chest computed tomography (CT) was conducted, under the suspicion of Harlequin syndrome in combination with Horner syndrome, to derive the diagnosis of a right lung apex tumor. This case showed that history taking and physical examination are very important in the emergency department. It is particularly vital to observe the microchanges in the patient's symptoms and signs. It is also imperative to reassess the patient whose symptoms fail to improve under treatment, to look for other underlying lesions.

Neuropathologic correlates for diffusion tensor imaging in postinfectious encephalopathy.

Acute necrotizing encephalopathy and acute disseminated encephalomyelitis are 2 rare types of acute postinfectious encephalopathy in children. Acute necrotizing encephalopathy is characterized by multiple symmetric lesions in the thalami, putamena, cerebral and cerebellar white matter, and brainstem. Acute disseminated encephalomyelitis is an immune-mediated demyelinating central nervous system disorder that predominantly affects the white matter. Diffusion magnetic resonance imaging is sensitive to measuring water diffusion in the central nervous system in human and animal models. Recent studies have demonstrated that by using an analytical approach to directional diffusivity-derived parameters, the axial diffusivity and the radial diffusivity, one can assess the extent of axonal or myelin injury in the central nervous system white matter. We applied directional diffusivity to acute necrotizing encephalopathy, acute disseminated encephalomyelitis, and control subjects correlating with neuropathology findings. In acute necrotizing encephalopathy, axonal injury without demyelination, noted on biopsy samples of brain tissue, was suggested by a decreased apparent diffusion coefficient, unchanged fractional anisotropy, and decreased axial and radial diffusivity. In acute disseminated encephalomyelitis, an increased apparent diffusion coefficient, decreased fractional anisotropy, unchanged axial diffusivity, and markedly increased radial diffusivity compatible with active inflammatory demyelination were noted, consistent with tissue biopsy sample neuropathology. In conclusion, diffusion tensor parameters can potentially depict more microstructural changes than conventional magnetic resonance imaging in postinfectious encephalopathy in children.