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Objective: Lower serum low-density lipoprotein cholesterol (LDL-C) levels are associated with increased intracerebral hemorrhage (ICH) risk. However, reverse causality and residual confounding has not attracted public attention. Therefore, we assessed whether people with LDL-C have increased risk of mortality adjusting for potential confounders using two large Taiwan cohorts.Methods: The Mei-Jhao (MJ) cohort has 414,372 adults participating in a medical screening program with 378 ICH deaths within 15 years of follow-up (1994–2008). Cox proportional hazards regressions estimated hazard death ratios according to LDL-C levels. We identified 4,606 ICH patients from the Taiwan Stroke Registry (TSR) and analyzed the impact of LDL-C on 3-month mortality.Results: Low cholesterol (LDL-C

The Asia Pacific Stroke Organization is the largest international and professional stroke group in the region. It has worked consistently over the last 10 years to gain visibility and reliability across the Asia Pacific and beyond. The 10 year journey will be reviewed in the background of many internal and external developments including changes in Asia Pacific stroke epidemiology, stroke care systems, stroke service developments as well as major research studies in the Asia Pacific.

Cardiovascular fitness exerts directly beneficial effects on functional and cognitive outcomes in patients of chronic stroke. However, the effect of early rehabilitation on cardiovascular function has not yet been thoroughly examined. We tested whether complementary rehabilitation program could influence cardiovascular fitness in an early stage of stroke patients. The associations for post-acute stroke functional recovery with cardiovascular fitness were explored. Thirty-seven patients with mean poststroke interval of 8.6 ± 3.8 days underwent inpatient rehabilitation of 22.8 ± 3.8 days. Functional outcomes of 15.3 points (17.2%) in functional independence measure improved after rehabilitation program. The therapeutic cardiovascular fitness was determined in ramp exercise test on a cycling ergometer. Peak oxygen uptake (V˙O2peak) significantly increased by 24.8% after early stroke rehabilitation. Multivariate regression analysis was performed to assess for associations of functional improvement with respect to change in V˙O2peak and extremities motor impairment. V˙O2peak gain accounted for more functional recovery than extremities motor improvement (R2 = 0.42). In conclusion, these results suggest that cardiovascular fitness appears to increase after complementary program in early stroke rehabilitation, and better cardiovascular fitness may be associated with greater functional improvement. Keywords: Fitness, Oxygen uptake, Rehabilitation, Stroke

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 (

The combined effects of metabolic syndrome and the apolipoprotein E and CYP46 genotypes on the risk of cognitive decline has yet to be determined among Taiwanese Chinese. Two hundred and nine mentally healthy middle-aged and older adults were assessed for metabolic syndrome, cognitive function using the Cognitive Abilities Screening Instrument, Mini-Mental State Examination, ApoE, and CYP46 polymorphisms. There were no differences in cognitive performance, ApoE epsilon4 (ε4) carrier status, or CYP46 genotypes between participants with and those without metabolic syndrome. The ε4 carriers and participants with the AA allele of CYP46 had significantly lower mental manipulation score. Metabolic syndrome and ε4 had synergistic effects on cognitive decline. Therefore, the ε4 carriers and participants with the AA allele of CYP46 have decreased mental manipulation ability. The metabolic syndrome may play a role in subtle cognitive dysfunction in ε4 carriers among Taiwanese Chinese.

Vertigo can be a major presentation of posterior circulation stroke and can be easily misdiagnosed because of its complicated presentation. We thus prospectively assessed the predictive value of vertebral artery extracranial color-coded duplex sonography (ECCS) for the prediction of ischemic stroke-related vertigo. The inclusion criteria were: (1) a sensation of whirling (vertigo); (2) intractable vertigo for more than 1 hour despite appropriate treatment; and (3) those who could complete cranial magnetic resonance imaging (MRI) and vertebral artery (V2 segment) ECCS studies. Eventually, 76 consecutive participants with vertigo were enrolled from Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan between August 2010 and August 2011. Demographic data, neurological symptoms, neurologic examinations, and V2 ECCS were assessed. We chose the parameters of peak systolic velocity (PSV), end diastolic velocity (EDV), PSV/EDV, mean velocity (MV), resistance index (RI), and pulsatility index (PI) to represent the hemodynamics. Values from both sides of V2 segments were averaged. We then calculated the average RI (aRI), average PI (aPI), average PSV (aPSV)/EDV, and average (aMV). Axial and coronal diffusion-weighted MRI findings determined the existence of acute ischemic stroke. We grouped and analyzed participants in two ways (way I and way II analyses) based on the diffusion-weighted MRI findings (to determine whether there was acute stroke) and neurological examinations. Using way I analysis, the “MRI (+)” group had significantly higher impedance (aRI, aPI, and aPSV/EDV ratio) and lower velocity (aPSV, aEDV, and aMV(PSV + EDV/2)), compared to the “MRI (–)” group. The cutoff value/sensitivity/specificity of aPSV, aEDV, aMV, aPI, aRI, and aPSV/EDV between the MRI (+) and MRI (–) groups were 41.15/61.5/66.0 (p = 0.0101), 14.55/69.2/72.0 (p = 0.0003), 29.10/92.1/38.0 (p = 0.0013), 1.07/76.9/64.0 (p = 0.0066), 0.62/76.9/64.0 (p = 0.0076), and 2.69/80.8/66.0 (p = 0.0068), respectively. Using way II analysis, lower aEDV and aMV, and higher aRI, aPI, and aPSV/EDV ratio could determine the “MRI (+) without focal signs” group. The cutoff value/sensitivity/specificity of aEDV, aMV, aPI, aRI, and aPSV/EDV between the MRI (+) without focal signs and MRI (–) groups were 9.10/71.4/96.0 (p = 0.0005), 15.65/57.1/96.0 (p = 0.0124), 1.10/100/70.0 (p = 0.0002), 0.64/100/70.0 (p = 0.0023), and 2.80/100/70.0 (p = 0.0017), respectively. In conclusion, using demographic data and clinical symptoms, it was difficult to determine the patients with ischemic stroke-related vertigo. Although neurological examinations still have diagnostic value, the high impedance and low velocity pattern of V2 ECCS can be an add-on method for the screening of acute ischemic stroke-related vertigo, even for those without focal neurological signs.

Frontal lobes are great and are a late-developing region of the neocortex that play a critical role in human behavior and executive function. The aim of this study was to clarify the role of event-related potentials (ERPs) in executive dysfunction and its relationship between generator mechanism and cognitive significance. We recruited 20 patients with frontal lobe lesion (FLL) and 27 age-matched controls. All patients submitted to comprehensive Frontal Test Battery and auditory ERPs measurement. In comparison with controls, the patients with FLL had significantly decreased executive function and manifested the delay of P300 latency, which reflected a delay of mental processing speed in these patients. Our findings suggest that patients with FLL may have prolonged P300 latency, which has a good correlation with executive dysfunction, poor performance, and longer P300 latencies. P300 ERPs are considered to be a useful method to identify the alteration of frontal-parietal connection.

Circadian variation of the onset time of acute ischemic stroke has been well studied. However, little is mentioned about the circadian variation of discharge-stroke severity and discharge-functional status. This study evaluated the impact of onset time on discharge-stroke severity and the functional status of acute ischemic stroke. Brain magnetic resonance imaging was performed on 274 acute ischemic stroke patients (66.42% male; mean age = 64.81 ± 12.80 years). All times of onset were assigned to 4-hourly periods (six groups) starting from midnight. Stroke severity/functional status was evaluated on admission and discharge using the National Institute of Health Stroke Scale (NIHSS) score/modified Rankin Scale (mRS) and Barthel Index (BI), respectively. Using mRS, but not NIHSS score and BI, it was possible to differentiate the best and worst groups on discharge. Patients in group 2 (4 to

Cardiac autonomic dysfunction is a common complication after acute ischemic stroke (IS). Prior investigators have emphasized that infarction of brain stem or hemispheres with insular involvement is related to this dysfunction and may predict poor clinical outcome. From the viewpoint of stroke physicians, however, all stroke patients, particularly large-artery atherosclerosis (LAA) should be monitored for possible cardiac complications after acute IS. This study aimed to investigate cardiac autonomic impaction in patients with acute IS and to make the comparison between LAA and small-vessel occlusion (SVO) subtypes. Of the 126 acute IS patients prospectively enrolled in this study, 32 had LAA, 56 had SVO, and 38 had undetermined etiology according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Cardiac autonomic function of all patients was assessed by measuring heart rate variability (HRV). The low- and high-frequency components of HRV in all stroke patients were significantly lower than those of control subjects after comparing multivariable models, including additional adjustments for age, gender, and all risk factors. There were no significant differences on HRV between LAA and SVO although post hoc comparisons showed that stroke patients of SVO had increased sympathetic modulation and reduced vagal activity. In conclusion, in acute IS patients, both LAA and SVO are predisposed to have cardiac autonomic dysfunction, manifesting as abnormalities in HRV, whether in hemispheric or brain stem lesions. Stroke patients of SVO are at higher risks of cardiac abnormalities, which might suggest an early cardiac dysfunction because of long-term hypertension. The HF component of HRV thought to be for vagal control might be a cardinal marker for predicting cardiac autonomic dysfunction after acute IS. Short-term HRV spectral analysis is a convenient approach for stroke clinicians to assess autonomic function in acute stroke. Long-term follow-up for HRV and clinical outcome relative to LAA and SVO stroke subtypes is warranted, particularly when an abnormal HRV is found at admission.

In the era of thrombolytic therapy for hyperacute ischemic stroke, most investigators have focused their attention on the factors influencing mortality and functional outcomes in patients treated with thrombolysis, but very few have focused on these factors among patients not receiving thrombolysis. The aim of this study was to investigate the prognostic factors for mortality in all hyperacute stroke patients with or without thrombolysis. In 2005, we enrolled 101 ischemic stroke patients (43 females, 58 males; mean age, 68 years) who were transported to the emergency department (ED) within 4 hours of symptom onset. The overall in-hospital mortality rate was 17.8% (18/101). According to t test analysis, age (p = 0.034), time interval from neurologist consultation (p < 0.0001) and ED to ward admission (p = 0.001), Glasgow coma scale (GCS) (p = 0.001), National Institutes of Health Stroke Scale (NIHSS) (p < 0.0001) and the sum of major risk factors of cerebrovascular disease (CVD) (p < 0.0001) were significantly different between mortality and survivor groups. Further χ2 test analysis revealed significant differences in the presenting consciousness disturbance (p = 0.001), place of attack (p = 0.04), and referral transportation (p = 0.008) between these groups. In conclusion, old age, delay between neurologist consultation and ward admission, severity of stroke, and multiple risk factors of CVD are significant risk factors for in-hospital mortality. Conversely, being free of initial consciousness disturbance, living in an urban area, and having direct transportation to a stroke center are protective factors in survivors. The concept of “brain attack” should be re-emphasized among ED physicians. The interconnection between stroke centers and emergency medical systems (EMS) should be more tightly built to promote timely management for hyperacute stroke care.

The biggest hurdle for early hospital presentation is the narrow therapeutic window after stroke. The aims of our study were to investigate the time lags and the factors causing pre‐hospital and emergency department (ED) delay during acute ischemic stroke attack. Between June 2004 and October 2005, we prospectively studied 129 acute ischemic stroke patients who presented to the ED of the study hospital within 4 hours after symptom onset. Chi‐square testing for trend, uni‐variate and multiple logistic regression analyses was performed to evaluate the factors influencing delays in the ED presentation of acute ischemic stroke patients. The median time from symptom onset to ED arrival was 71 (mean ± SD, 82.7 ± 57.7) minutes. The median times from ED arrival to neurologic consultation, computed tomography scan, electrocardiogram, and laboratory data completion were 10 (11.3±9.9) minutes, 17 (9.6±11.3) minutes, 14 (23.3±55) minutes, and 39 (44.4±24.5) minutes, respectively. Univariate and multiple logistic regression models revealed that age < 65 years, illiteracy and awakening with symptoms were the most significant factors related to a delay in ED presentation. This study indicates that 2 hours of pre‐hospital delay is the cutoff point for thrombolytic therapy. Organization of a stroke team and standardized stroke pathways may help to shorten in‐hospital time consumption. Educational efforts should not only focus on the public, but also on the training of ED physicians and other medical personnel.

The aim of this study was to clarify whether the apolipoprotein E gene (APOE) is related to ischemic stroke subtypes in Taiwan's Chinese population. Using the classification of Cerebrovascular Diseases III, 143 patients with lacunar infarction, 114 patients with atherothrombotic infarction, and 112 healthy controls were enrolled. APOE genotype was determined using polymerase chain reaction. Regarding the distribution of APOE genotypes, the frequency of ϵ3/ϵ4 genotypes in lacunar patients was significantly different from that in control subjects, by logistic regression, using ϵ3/ϵ3 as a reference group. There was no significant difference between atherothrombotic patients and the control group in the distribution of APOE genotypes or alleles. The present finding suggests that there is a probable association between ϵ3/ϵ4 genotype and lacunar infarcts, but not atherothrombotic infarcts. This indicates that genetic factors may play a role, at least partially, in lacunar infarction in Taiwan's Chinese population.

Successful treatment of cough syncope depends on the correction of various pathogenetic mechanisms among different patients. The valsalva maneuver (VM), which elicits hemodynamic responses mimicking coughs, has potential for investigating the individual pathogenesis of cough syncope. Eighteen consecutive patients suffering from cough-induced syncope were examined. All patients were asked to cough and to perform VM several times under continuous cerebral blood-flow velocity and blood pressure (BP) monitoring by transcranial Doppler and finger plethysmography. Eight patients demonstrated abnormal VM characterized by the absent BP overshoot following the relief of straining. Patients demonstrating abnormal VM had delayed BP recovery after cough (median, 16.4; range, 8.7–25.6 seconds) compared to those demonstrating normal VM (2.6, 1.3–3.8 seconds, p < 0.001). Seven of the 10 patients exhibiting normal BP overshoot during VM had stenotic arterial lesions in the cerebral or coronary circulation, whereas only one of the eight patients demonstrating absent BP overshoot had coronary artery disease (70% vs. 12.5%, p = 0.025). Other clinical profiles, body mass index, frequency of obstructive pulmonary disease and valsalva ratio did not differ between patients featuring normal and absent BP overshoot. In conclusion, the pathogenesis of cough syncope could be different between patients with normal and abnormal VM responses. Patients who had no BP overshoot during VM sustained prolonged hypotension after cough. The VM helps in discriminating among pathogenic mechanisms and guiding investigation and treatment for cough syncope patients.

Estrogen is involved in neuron plasticity and can promote neuronal survival in stroke. Its actions are mostly exerted via estrogen receptor alpha (ERα). Previous animal studies have shown that ERα is upregulated by DNA demethylation following ischemic injury. This study investigated the methylation levels in the ERα promoter in the peripheral blood of ischemic stroke patients.The study included 201 ischemic stroke patients, and 217 age- and sex-comparable healthy controls. The quantitative methylation level in the 14 CpG sites of the ERα promoter was measured by pyrosequencing in each participant. Multivariate regression model was used to adjust for stroke traditional risk factors. Stroke subtypes and sex-specific analysis were also conducted.The results demonstrated that the stroke cases had a lower ERα methylation level than controls in all 14 CpG sites, and site 13 and site 14 had significant adjusted p-values of 0.035 and 0.026, respectively. Stroke subtypes analysis showed that large-artery atherosclerosis and cardio-embolic subtypes had significantly lower methylation levels than the healthy controls at CpG site 5, site 9, site 12, site 13 and site 14 with adjusted p = 0.039, 0.009, 0.025, 0.046 and 0.027 respectively. However, the methylation level for the patients with small vessel subtype was not significant. We combined the methylation data from the above five sites for further sex-specific analysis. The results showed that the significant association only existed in women (adjusted p = 0.011), but not in men (adjusted p = 0.300).Female stroke cases have lower ERα methylation levels than those in the controls, especially in large-artery and cardio-embolic stroke subtypes. The study implies that women suffering from ischemic stroke of specific subtype may undergo different protective mechanisms to reduce the brain injury.

Neurologic signs and symptoms are common in acute malarial infection. However, after the parasites have been cleared from the blood and patients recover full consciousness, neurologic or psychiatric symptoms may occur or recur within 2 months after the acute illness. This phenomenon is called “postmalaria neurologic syndrome” (PMNS). We present a 50-year-old man who returned from the Republic of Malawi and soon developed Plasmodium falciparum malaria. Cerebral malaria, renal failure, hepatic failure, diffuse intravascular coagulation with thrombocytopenia, and upper gastrointestinal bleeding were noted during the acute stage. He was admitted to the infectious diseases ward and treated for 3 weeks. He was free from clinical general symptoms and parasites in blood smear when discharged. However, 2 weeks after discharge, he began to experience severe headache, dizziness, diplopia, mild hand tremor, unsteady gait, and easy falling. When readmitted to the neurologic ward, he presented with irritability, delirium, visual hallucination, and strange behavior. Neurologic examination was normal except for mild general weakness and evident truncal ataxia when walking. Brain magnetic resonance imaging revealed no structural lesions, and electroencephalography showed diffuse cortical dysfunction. Cerebral spinal fluid profile exhibited cytoalbuminologic dissociation. Brain single photon emission computed tomography showed diffuse cerebral parenchymal disorder. Nerve conduction studies revealed early sensory predominant polyneuropathy. The unsteadiness persisted for the initial 2 weeks of hospitalization until corticosteroid was administered. Intravenous methylprednisolone (80 mg/day) was continued for 3 days, followed by oral prednisolone (45 mg/day). His unsteadiness improved gradually after medication, and he absconded from the hospital on the 9th day of corticosteroid treatment with clear consciousness and free ambulation. The manifestation of PMNS is diverse and may present as an acute confusional state or psychosis, generalized seizure, fine tremors, cerebellar syndromes, postural hypotension, or malarial polyneuritis. Although the neurologic syndrome is primarily self-limited in most cases, corticosteroid may be beneficial in reversing PMNS.

Seizures and focal neurologic deficits may be the complications of neurosyphilis, but status epilepticus as a presenting picture of neurosyphilis is rare. We describe a 41-year-old man with an acute onset of expressive dysphasia, followed by persistent seizure state and severe complications of systemic medical problems. An extensive laboratory evaluation confirmed the diagnosis of neurosyphilis and diabetes mellitus. Brain magnetic resonance imaging showed edematous change in the left cingulate gyrus, left temporal lobe, and peri-Rolandic area, which suggested an inflammatory process. Due to varied clinical manifestations of neurosyphilis, we underscore the importance of considering neurosyphilis among the possible causes of status epilepticus and any central nervous system diseases.

Although the Blessed Dementia Rating Scale (BDRS), a clinical screening instrument, has been applied extensively, no suitable cut-off values and clinical application have been proposed, particularly in mild cognitive impairment (MCI), the precursor of dementia. The BDRS, Mini Mental State Examination (MMSE), and Clinical Dementia Rating Scale (CDR) were administrated in people aged 65 years and above, who were enrolled from southern Taiwan with multistep stratified random sampling and followed-up for 2 years. All subjects (total number = 3,027), with new onset of MCI (defined as CDR = 0.5) in the first year and dementia (defined as CDR ≥ 1) in the second and third years were subjected to statistical analysis. In distinguishing normal from MCI, except in the literate group aged 65-74 years, MMSE was superior to BDRS, with cut-off values of 1 in both literate groups aged 65-74 years and ≥ 75 years, and 1.5 and 2 in less educated groups aged 65-74 and ≥ 75 years, respectively. In distinguishing MCI from dementia, BDRS had cut-off values of 2.5 in both literate groups aged 65-74 and ≥ 75 years, and 2.5 and 3 in less educated groups aged 65-74 and ≥ 75 years, respectively. These values were better than those for MMSE in all groups. BDRS might be considered as a better tool than MMSE to screen for MCI and dementia in the increasing proportion of literate elderly aged 65-74 years in the aging population.

Cerebral venous thrombosis (CVT) is not uncommon, but CVT associated with bilateral internal jugular vein stenosis (BIJVS) is rare. Bilateral internal jugular vein stenting is also a rare procedure. We report on a patient with CVT associated with BIJVS, who was treated successfully using direct thrombolysis and bilateral internal jugular vein stenting.

BackgroundEstrogen receptor α (ERα) has been shown to protect against atherosclerosis. Methylation of the ERα gene can reduce ERα expression leading to a higher risk for cardiovascular disease. Recently, microRNAs have been found to regulate DNA methyltransferases (DNMTs) and thus control methylation status in several genes. We first searched for microRNAs involved in DNMT-associated DNA methylation in the ERα gene. We also tested whether statin and a traditional Chinese medicine (San-Huang-Xie-Xin-Tang, SHXXT) could exert a therapeutic effect on microRNA, DNMT and ERα methylation.Methodology/principal findingsThe ERα expression was decreased and ERα methylation was increased in LPS-treated human aortic smooth muscle cells (HASMCs) and the aorta from rats under a high-fat diet. MicroRNA-152 was found to be down regulated in the LPS-treated HASMCs. We validated that microRNA-152 can knock down DNMT1 in HASMCs leading to hypermethylation of the ERα gene. Statin had no effect on microRNA-152, DNMT1 or ERα expression. On the contrary, SHXXT could restore microRNA-152, decrease DNMT1 and increase ERα expression in both cellular and animal studies.Conclusions/significanceThe present study showed that microRNA-152 decreases under the pro-atherosclerotic conditions. The reduced microRNA-152 can lose an inhibitory effect on DNA methyltransferase, which leads to hypermethylation of the ERα gene and a decrease of ERα level. Although statin can not reverse these cascade proatherosclerotic changes, the SHXXT shows a promising effect to inhibit this unwanted signaling pathway.

BACKGROUND: Chromosome 9p21 has recently been shown to be a risk region for a broad range of vascular diseases. Since carotid intima-media thickness (IMT) and plaque are independent predictors for vascular diseases, the association between 9p21 and these two phenotypes was investigated. METHODOLOGY/PRINCIPAL FINDINGS: Carotid segment-specific IMT and plaques were obtained in 1083 stroke- and myocardial infarction-free volunteers. We tested the genotypes and haplotypes of key single nucleotide polymorphisms (SNPs) on chromosome 9p21 for the associations with carotid IMT and plaque. Multivariate permutation analyses demonstrated that carriers of the T allele of SNP rs1333040 were significantly associated with thicker common carotid artery (CCA) IMT (p=0.021) and internal carotid artery (ICA) IMT (p=0.033). The risk G allele of SNP rs2383207 was associated with ICA IMT (p=0.007). Carriers of the C allele of SNP rs1333049 were found to be significantly associated with thicker ICA IMT (p=0.010) and the greater risk for the presence of carotid plaque (OR=1.57 for heterozygous carriers; OR=1.75 for homozygous carriers). Haplotype analysis showed a global p value of 0.031 for ICA IMT and 0.115 for the presence of carotid plaque. Comparing with the other haplotypes, the risk TGC haplotype yielded an adjusted p value of 0.011 and 0.017 for thicker ICA IMT and the presence of carotid plaque respectively. Further analyzing the data separated by sex, the results were significant only in men but not in women. CONCLUSIONS: Chromosome 9p21 had a significant association with carotid atherosclerosis, especially ICA IMT. Furthermore, such genetic effect was in a gender-specific manner in the Han Chinese population.

Background: Stroke is one of the leading causes of mortality and neurologic deficits. Management measures to improve neurologic outcomes are in great need. Our previous intervention trial in elderly subjects successfully used salt as a carrier for potassium, demonstrating a 41% reduction in cardiovascular mortality by switching to potassium-enriched salt. Dietary magnesium has been associated with lowered diabetes and/or stroke risk in humans and with neuroprotection in animals. Objective: Because a large proportion of Taiwanese individuals are in marginal deficiency states for potassium and for magnesium and salt is a good carrier for minerals, it is justifiable to study whether further enriching salt with magnesium at an amount near the Dietary Reference Intake (DRI) amount may provide additional benefit for stroke recovery. Design: This was a double-blind, randomized controlled trial comprising 291 discharged stroke patients with modified Rankin scale (mRS) ≤4. There were 3 arms: 1) regular salt (Na salt) (n = 99), 2) potassium-enriched salt (K salt) (n = 97), and 3) potassium- and magnesium-enriched salt (K/Mg salt) (n = 95). The NIH Stroke Scale (NIHSS), Barthel Index (BI), and mRS were evaluated at discharge, at 3 mo, and at 6 mo. A good neurologic performance was defined by NIHSS = 0, BI = 100, and mRS ≤1. Results: After the 6-mo intervention, the proportion of patients with good neurologic performance increased in a greater magnitude in the K/Mg salt group than in the K salt group and the Na salt group, in that order. The K/Mg salt group had a significantly increased OR (2.25; 95% CI: 1.09, 4.67) of achieving good neurologic performance compared with the Na salt group. But the effect of K salt alone (OR: 1.58; 95% CI: 0.77, 3.22) was not significant. Conclusions: This study suggests that providing the DRI amount of magnesium and potassium together long term is beneficial for stroke patient recovery from neurologic deficits. This trial was registered at clinicaltrials.gov as NCT02910427. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase-2 (MMP-2) is involved in the pathophysiology of stroke. Previous studies have shown that MMP-2 activity is increased in stroke; however, evidence of epigenetic regulation of the MMP-2 in stroke is still limited. We examined methylation of the MMP-2 promoter in patients with ischemic stroke. This study included 298 patients with ischemic stroke and 258 age-matched and sex-matched controls. MMP-2 promoter methylation levels were measured by pyrosequencing at eight potential cytosine-guanine (CpG) sites. Multivariate regression analysis was used to adjust for general stroke risk factors, and the specific effects of sex and stroke subtype were analysed. The methylation levels of MMP-2 in the peripheral blood of the patients with stroke were lower than controls in all eight CpG sites, especially at site 1, site 5, site 7, and site 8 (adjusted p=0.036, 0.002, 0.021, and 0.041, respectively). In subgroup analysis by sex, a significant association was found only in men but not in women. When the stroke subtype was considered, men with small-vessel stroke had significantly lower methylation levels at all MMP-2 CpG sites than the controls (3.01% vs 3.65%, adjusted p=0.018). Although men with large-artery atherosclerosis stroke also had lower MMP-2 methylation levels, no significant difference was found (3.25% vs 3.65%, adjusted p=0.253). Demethylation of the MMP-2 promoter in patients with ischemic stroke was in a sex and stroke subtype-specific manners. These findings may add to the understanding of epigenetic modification of MMP-2 on ischemic stroke. [ABSTRACT FROM AUTHOR]

Hypertension is a major risk factor for strokes and myocardial infarction (MI). Given its effectiveness and safety profile, the calcium channel blocker amlodipine is among the most frequently prescribed antihypertensive drugs. This analysis was conducted to determine the costs and quality-adjusted life years (QALYs) associated with the use of amlodipine and valsartan, an angiotensin II receptor blocker, in preventing stroke and MI in Taiwanese hypertensive patients. A state transition (Markov) model was developed to compare the 5-year costs and QALYs for amlodipine and valsartan. Effectiveness data were based on the NAGOYA HEART Study, local studies, and a published meta-analysis. Utility data and costs of MI and stroke were retrieved from the published literature. Medical costs were based on the literature and inflated to 2011 prices; drug costs were based on National Health Insurance prices in 2014. A 3% discount rate was used for costs and QALYs and a third-party payer perspective adopted. One-way sensitivity and scenario analyses were conducted. Compared with valsartan, amlodipine was associated with cost savings of New Taiwan Dollars (NTD) 2,251 per patient per year: costs were NTD 4,296 and NTD 6,547 per patient per year for amlodipine and valsartan users, respectively. Fewer cardiovascular events were reported in patients receiving amlodipine versus valsartan (342 vs 413 per 10,000 patients over 5 years, respectively). Amlodipine had a net gain of 58 QALYs versus valsartan per 10,000 patients over 5 years. Sensitivity analyses showed that the discount rate and cohort age had a larger effect on total cost and cost difference than on QALYs. However, amlodipine results were more favorable than valsartan irrespective of discount rate or cohort age. When administered to Taiwanese patients for hypertension control, amlodipine was associated with lower cost and more QALYs compared with valsartan due to a lower risk of stroke and MI events. [ABSTRACT FROM AUTHOR]

Objectives: The rate of recombinant tissue plasminogen activator (rtPA) use for stroke is low among the Chinese-Taiwanese. The study objective was to determine if less restrictive exclusion criteria for rtPA would increase eligibility and the rate of treatment. Methods: This retrospective before-and-after study was conducted from 2006 to 2009. The authors compared stroke patients treated under the old rtPA exclusion criteria (January 2006 to December 2008) with those treated with less restrictive rtPA exclusion criteria (January to December 2009). Rates of eligibility and treatment and reasons for exclusion from rtPA between the two phases were assessed. Results: Of 461 eligible patients during the study period, 333 were evaluated by the old criteria and 128 were evaluated by the less restrictive criteria. Minor or improving stroke was the primary exclusion reason in both groups (194/333, 58% vs. 70/128, 55%). Eligibility for rtPA was increased in the less restrictive criteria (35/127, 27%, 95% confidence interval [CI] = 20% to 36%) compared to the old criteria (40/333, 12%, 95% CI = 8.7% to 16%; p = 0.0001). Fewer patients were excluded due to old age in the less restrictive criteria (0/128, 0%) compared to the old criteria (37/333, 11%; p = 0.0001). The rate of consent refusal increased in the less restrictive criteria (27/128, 21%, 95% CI = 14% to 29%) compared to the old criteria (23/333, 6.9%, 95% CI = 4.4% to 10%; p < 0.0001). Rate of rtPA treatment was unchanged between the less restrictive criteria (8/128, 6.3%, 95% CI = 2.7% to 12%) and the old criteria (17/333, 5.1%, 95% CI = 3% to 8%; p = 0.63). Conclusions: Increasing eligibility for rtPA does not increase the rate of treatment, possibly due to the high symptomatic intracerebral hemorrhage rate among Chinese-Taiwanese, which is a major concern among emergency physicians (EPs), neurologists, and patients. Dealing with perceived safety issues of rtPA is crucial before the rate of treatment can be increased. [ABSTRACT FROM AUTHOR]

Background: Growing evidence suggests that white matter hyperintensities (WMHs) are implicated in stroke recurrence and mortality, and their location can be a critical factor. This study evaluated the impact of periventricular WMHs (PVWMHs) and subcortical WMHs (SWMHs) on poststroke functional outcomes. Methods: Brain MRI was performed on 187 acute ischemic stroke patients (57.8% male; mean age = 64.3 years) recruited from the Kaohsiung Municipal Hsiao-Kang Hospital from February 2007 to January 2008. A Fazekas score ≥2 in the periventrcular or subcortical white matter was taken as presence of WMHs. Demographic data and risk factors for stroke were assessed. Functional stroke outcomes were evaluated 30 days after stroke using the Barthel Index (BI) and the modifiedRankin Scale (mRS). Results: WMHs were inversely linked to favorable functional outcome measured by mRS (p = 0.001) and BI (p = 0.003). Evaluating different locations, PVWMHs were associated with unfavorable functional outcomes (p = 0.002, mRS; p = 0.001, BI). SWMHs were related to mRS (p = 0.026) but not BI (p = 0.069). After controlling other stroke risk factors, infarct volumes and initial stroke severity, PVWMHs were a significant indicator for both mRS (OR = 2.76; 95% CI = 1.03–7.40) and BI (OR = 3.07; 95% CI = 1.13–8.40), but SWMHs were not. Conclusions: Unfavorable functional stroke outcome is associated with MRI WMHs. In terms of location, PVWMHs but not SWMHs are related to functional stroke outcome. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Currently, no practical biomarker is available for the diagnosis of acute ischemic stroke. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has being applied extensively to analyze large biomolecules such as proteins. The technique is likely to be of remarkable value as indicators of systemic processes such as atherosclerosis and stroke. The aim of this study is to identify potential protein biomarkers for ischemic stroke diagnosis utilizing MALDITOF MS. Serum samples obtained from acute ischemic stroke patients (n = 47) and controls (n = 34) were analyzed by MALDI-TOF MS. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS), subtype by the Trial of Org 10172 in Acute Stroke Treatment (TOAST), functional outcome by the modified Rankin Scale (mRS) and infarct volume by the diffusion-weighted images. Risk factors and routine laboratory data of the stroke patients were registered prospectively. The peaks of hemoglobin (Hb) α-chain and β-chain were differentially expressed between stroke patients and controls ( p < 0.0001). Hb ions were detected in the samples collected from 33 (70.2 %) stroke patients and 5 (14.7 %) controls. The sensitivity is 70.2 % and the specificity is 85.3 %. Among stroke patients, there is no significant correlation ( p > 0.05) between Hb peaks and the NIHSS, TOAST, mRS, stroke risk factors, infarct volume, infarct location and laboratory data. Serum free Hb may serve as a novel potential biomarker for the diagnosis of acute ischemic stroke. The clinical value of this potential biomarker may be clarified by further studies quantifying serum free Hb levels. [ABSTRACT FROM AUTHOR]

Background: The eligibility for recombinant tissue plasminogen activator (rtPA) is rare. We analyze the reasons for exclusion from rtPA among patients who were admitted to our hospital within 3 h. Methods: A strict protocol for hyperacute stroke was set in a university teaching hospital. Consecutive patients activating the protocol from June 2004 to October 2005 were prospectively registered and entered into a computerized database. The patients were excluded from rtPA according to the modified exclusion criteria from the National Institute of Neurological Disorders and Stroke rtPA trial. Results: Of the 182 patients activating the protocol, only 11 (6.04%) received intravenous rtPA and 4 (2.2%) IA thrombolysis. Patients were excluded for multiple reasons, and the main reasons for exclusion were minor or improving stroke (46.15%), hypertension (35.16%), insufficient time to complete studies or onset beyond 3 h after reconfirmation (24.17%) and intracranial hemorrhage (15.93%). Of 167 excluded patients, 72 (43.11%) were excluded by a single criterion, 53 (31.73%) by 2 criteria and 29 (17.36%) by 3 criteria. The mean time from hospital arrival to presentation to a neurologist was 9.24 ± 15.11 min (n = 164, median = 8.00, mode = 10, range = 0–65). The mean time from hospital arrival to computed tomography (CT) was 21.67 ± 23.95 min (n = 167, median = 20.00, mode = 10, range = 4–68). Conclusion: An intrahospital stroke code was implemented to minimize intrahospital delay. However, only 11 patients received intravenous rtPA and 4 IA thrombolysis at our hospital from June 2004 to October 2005. The result brings into question the neurologist’s conservative interpretation of the criteria and the necessity to clearly define some criteria. Furthermore an intrahospital stroke code should also be implemented for inpatients to maximize the eligibility for rtPA. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]