TIA Group Research Articles

Asymmetric and symmetric dimethylarginine as markers of endothelial dysfunction in cerebrovascular disease: A prospective study

Background and aimAsymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) have been proposed as mediators of endothelial dysfunction. In this study, we aimed to investigate the diagnostic and prognostic role of ADMA and SDMA in acute cerebrovascular disease. Methods and resultsA prospective case-control study was performed, enrolling 48 patients affected by ischemic stroke with no cardioembolic origin, 20 patients affected by TIA, 40 subjects at high cardiovascular risk and 68 healthy subjects.ADMA levels were significantly lower in high-risk subjects (18.85 [11.78–22.83] μmol/L) than in patients with brain ischemic event, both transient (25.70 [13.15–40.20] μmol/L; p = 0.032) and permanent (24.50 [18.0–41.33] μmol/L; p = 0.001). SDMA levels were different not only between high-risk subjects and ischemic patients, but also between TIA and stroke patients, reaching higher levels in TIA group and lower levels in stroke group (1.15 [0.90–2.0] vs 0.68 [0.30–1.07] μmol/L; p < 0.001). SDMA was also correlated with short-term prognosis, with lower levels in case of adverse clinical course, evaluated by type of discharge (p = 0.009) and need of prolonged rehabilitation (p = 0.042). ConclusionsThe present study highlights the relationship between l-arginine, ADMA, SDMA and acute cerebrovascular events. Therefore, our results suggested a potential role of SDMA as a specific marker of transient ischemic damage and as a short-term positive prognostic marker.

New insights of metabolite abnormalities in the thalamus of rats with iminodiproprionitrile-induced tic disorders.

This study aimed to investigate pathological changes in the "Glutamate (Glu)-γ-aminobutyric acid (GABA)" loop and apply widely targeted metabolomic analysis technology to comprehensively explore metabolite abnormalities/ in the thalamus of rats with tic disorders (TD). Wistar rats were randomized into control, TD, and tiapride (Tia) groups. Iminodipropionitrile (IDPN) was used to induce TD in rats. The Tia group was administered tiapride. Neurotransmitter levels in the thalamus of rats in the three groups were measured using UPLC-3Q MS. And, the protein expression levels of Glu decarboxylase (GAD65/67) and GABA transporter protein (GAD-T) were measured using western blotting. The mRNA expression levels of these genes were evaluated using real-time polymerase chain reaction. Lastly, other metabolites in the thalamus were detected by widely targeted metabolomic analysis between TD and Control group rats. The Glu level, Glu/GABA ratio, and Asp level in the TD group were significantly higher (all p < 0.001) than those of the Control group, whereas the GABA and Gly levels were lower (p < 0.001 and p = 0.009, respectively). The Tia group exhibited a significant reduction in the Glu level (p = 0.001) compared with the TD group. The protein expression level of GAD67 in TD group was higher (p = 0.009) and the mRNA expression levels of GAD65, GAD67, and GAT-1 were lower (p < 0.05) than those of the Control group. The Tia group did not display any differences in GAD65, GAD67, or GAT-1 expression. Widely targeted metabolomic analysis revealed that 34 substances were abnornal between the TD and Control groups (9 upregulated and 25 downregulated). Neurosteroids (progesterone, corticosterone) exhibited distinct differences. Metabolite analysis using the Kyoto encyclopedia for genes and genomes indicated that the steroid hormone biosynthesis pathway may be involved in TD pathogenesis. This study revealed metabolic abnormalities in the thalamus of rats with TD. The interaction between neurotransmitters and neurosteroid biosynthesis represents a new direction for future studies.

Genetic Connections and Convergent Evolution of Tropical Indigenous Peoples in Asia.

Tropical indigenous peoples in Asia (TIA) attract much attention for their unique appearance, whereas their genetic history and adaptive evolution remain mysteries. We conducted a comprehensive study to characterize the genetic distinction and connection of broad geographical TIAs. Despite the diverse genetic makeup and large interarea genetic differentiation between the TIA groups, we identified a basal Asian ancestry (bASN) specifically shared by these populations. The bASN ancestry was relatively enriched in ancient Asian human genomes dated as early as ∼50,000 years before the present and diminished in more recent history. Notably, the bASN ancestry is unlikely to be derived from archaic hominins. Instead, we suggest it may be better modeled as a survived lineage of the initial peopling of Asia. Shared adaptations inherited from the ancient Asian ancestry were detected among the TIA groups (e.g., LIMS1 for hair morphology, and COL24A1 for bone formation), and they are enriched in neurological functions either at an identical locus (e.g., NKAIN3), or different loci in an identical gene (e.g., TENM4). The bASN ancestry could also have formed the substrate of the genetic architecture of the dark pigmentation observed in the TIA peoples. We hypothesize that phenotypic convergence of the dark pigmentation in TIAs could have resulted from parallel (e.g., DDB1/DAK) or genetic convergence driven by admixture (e.g., MTHFD1 and RAD18), new mutations (e.g., STK11), or notably purifying selection (e.g., MC1R). Our results provide new insights into the initial peopling of Asia and an advanced understanding of the phenotypic convergence of the TIA peoples.

"Glu/GABA-Gln" metabolic loop abnormalities in iminodipropionitrile (IDPN)-induced dyskinetic syndrome.

Iminodipropionitrile (IDPN)-induced dyskinetic syndrome is characterized by abnormal repetitive involuntary movements with abnormalities in the neuro-transmission. This study explored the mechanism of glutamate (Glu)/γ-aminobutyric acid (GABA)-glutamine (Gln) metabolic circuit in rat dyskinetic syndrome and the possible regulation mechanism of "tiapride (Tia)." Male Wistar rats were assigned to the control group, dyskinetic syndrome group, and Tia group. Dyskinetic syndrome was induced by injecting with 3,3'-iminodipropionitrile for 7days. Tia group was treated with tiapride, while the control and dyskinetic syndrome groups were gavaged with saline. Eventually the Glu, GABA, and Gln concentrations in striatum were detected using UPLC-3QMS, additionally another amino acid neurotransmitters (aspartate, glycine) were also detected. Expressions of glutamine synthetase (GS), glutamate transporter (EAAT2), glutamate decarboxylase (GAD65/67), and γ-aminobutyric acid transporter protein (GAD-T) were observed using Western blot and real-time polymerase chain reaction. The behavior test scores of dyskinetic syndrome group were increased compared with the control group. Tia group decreased the behavior test scores compared with dyskinetic syndrome group. For amino acid neuro-transmission, dyskinetic syndrome group increased Glu level (p < 0.01), decreased GABA level (p < 0.01), increased Glu/GABA ratio (p < 0.01), and decreased Asp level (p < 0.01) compared with control group. Tia group decreased Glu level (p < 0.01), increased GABA level (p < 0.01), decreased Glu/GABA ratio (p < 0.01), and increased Asp level (p < 0.05) compared with dyskinetic syndrome group. For Glu/GABA-Gln circuit, the protein and mRNA expression of GS and EAAT2 in dyskinetic syndrome group were decreased (p < 0.05). Tia group increased protein and mRNA expression level of GS (p < 0.05) and EAAT2 (p < 0.01). The rat dyskinetic syndrome has Glu/GABA-Gln abnormalities. "Tiapride" upregulated the protein expression of GS and EAAT2, reduce Glu levels, increase γ-GABA levels, and eventually improve amino acid neurotransmitter imbalance.

Gastrodin Attenuates Tourette Syndrome by Regulating EAATs and NMDA Receptors in the Striatum of Rats.

PurposeThis study explored whether gastrodin (Gas) could attenuate the symptoms of Tourette syndrome(TS) via the regulation of glutamate (Glu), its transporters (EAAT1 and EAAT2) and its receptors (NMDAR1, NMDAR2A and NMDAR2B) in rats.Materials and MethodsSeventy-five Wistar male rats were randomly divided into five groups (n=15 each): the control, TS, Tia (tiapride, 25mg/kg), Gas60 (gastrodin, 60mg/kg) and Gas120 groups (gastrodin, 120mg/kg). Rats in all groups except the control group received intraperitoneal injection of 3,3′-iminodipropionitrile (IDPN) for 7 consecutive days to establish the TS model. Thereafter, rats in the Tia, Gas60, and Gas120 groups were gavaged with 25mg/kg Tia, 60mg/kg Gas and 120mg/kg Gas for 28 days. Rats in the control and TS groups were gavaged with 0.9% normal saline. Behavioral evaluation was performed by using stereotypy scoring, nodding experiment and autonomic activity test. The Glu level was measured by UPLC-QqQ-MS analysis. The expression of EAAT1, EAAT2, NMDAR1, NMDAR2A and NMDAR2B was measured by Western blot and quantitative real-time PCR (qRT-PCR) analyses.ResultsThe results showed that rats with IDPN-induced TS exhibited an increase in stereotypy score, nodding numbers, number of times to enter the central area and autonomic total distance, which could be improved by Tia and Gas treatments. Furthermore, Tia and Gas treatments significantly decreased the IDPN-induced the increase in Glu levels in rats with TS. Furthermore, the decreased expression of EAAT1 and EAAT2 and increased expression of NMDAR1, NMDAR2A, and NMDAR2B in rats with TS induced by IDPN could be substantially altered by Tia and Gas treatments.ConclusionGas ameliorated the behavioral dysfunction of rats with TS by maintaining Glu at a normal level, upregulating the expression of EAAT1 and EAAT2, and downregulating the expression of NMDAR1, NMDAR2A and NMDAR2B.

A Novel Clinical Nomogram to Predict Transient Symptomatic Associated with Infarction: The ABCD3-SLOPE Score.

Background It is hard to differentiate transient symptoms associated with infarction (TSI) from transient ischemic stroke (TIA) without MRI in the early onset. However, they have distinct clinical outcomes and respond differently to therapeutics. Therefore, we aimed to develop a risk prediction model based on the clinical features to identify TSI. Methods We enrolled 230 consecutive patients with transient neurologic deficit in the Department of Neurology, Tongji University Affiliated Tenth People's Hospital from March 2014 to October 2019. All the patients were assigned into TIA group (DWI-negative) or TSI group (DWI-positive) based on MRI conducted within five days of onset. We summarized the clinical characteristics of TSI by univariate and multivariate analyses. And then, we developed and validated a nomogram to identify TSI by the logistic regression equation. Results Of the 230 patients, 41.3% were diagnosed with TSI. According to the multivariate analysis, four independent risk factors, including smoking history, low-density lipoprotein cholesterol, brain natriuretic peptide precursor, and ABCD3 score, were incorporated into a nomogram. We developed a predictive model named ABCD3-SLOPE. The calibration curve showed good agreement between nomogram prediction and observation. The concordance index (C-index) of the nomogram for TSI prediction was 0.77 (95% confidence interval, 0.70-0.83), and it was well-calibrated. Conclusions Smoking history, low-density lipoprotein cholesterol, brain natriuretic peptide precursor, and ABCD3 score were reliable risk factors for TSI. ABCD3-SLOPE was a potential tool to quantify the likelihood of TSI.

192 Interleukin-6 and C-Reactive Protein Predict all Cause Death and Poor Functional Outcome after Non-Severe Stroke and Transient Ischaemic Attack

Abstract Background Inflammation plays a role in the development of ischaemic cerebrovascular events. High sensitivity C-reactive protein (CRP) is known to predict recurrent events. Little data exists for more upstream serum markers of inflammation. Methods BIO-STROKE and BIO-TIA were multicentre prospective biomarker and imaging studies of patients with non-severe stroke, TIA and controls. Exclusion criteria were malignancy, infection, recent trauma / surgery, recurrent stroke before phlebotomy/MRI. Serum biomarkers analysed included Interleukin (IL) – 6, CRP, IL-1, IL-8, IL10, IL12p70, IFN and TNF.Plasma CRP and IL-6 were measured by mass spectrometry. Additional biomarkers were measured using ELISA. Follow up was performed at 7, 28, 90 days and 1 year. Results 680 patients (439 strokes, 241 TIAs) and 68 controls were included in the analysis. The median age was 70 for cases. Carotid stenosis was present in 23.6% of cases. Median CRP was 3.75mg/L, 2.36mg/l and 1.87mg/L in the stroke, TIA and control groups (p=&lt;0.001). Median IL-6 was 5.86pg/ml (stroke), 4.25pg/ml (TIA), 3.06pg/ml (control) (p=&lt;0.001). On multivariate cox regression analysis baseline IL6 and CRP were independent predictors of all cause death at 1 year with a HR of 1.005 (95% CI 1.002-1.007, p&lt;0.001).and 1.005(95% CI 1.002-1.007, p&lt;0.001) per unit increase. Both IL6 and CRP were associated with vascular death at 1 year. In adjusted analyses, IL6 and CRP were associated with poor functional outcome at 1 year (OR of 1.02(CI 1.01 -1.03) and 1.02(CI 1.01-1.03) per unit increase, for IL6 and CRP respectively). On adjusted analysis, when IL6 was analysed as quartiles, there was a strong association with death at 1 year with an OR 1.87 (95% CI 1.19-2.93).CRP, analysed as quartiles, demonstrated an OR for death at 1 year of 1.64 (1.10-2.46). Conclusion IL-6 and CRP may be a useful prognostic factor for the prediction of outcome and death after stroke at 1 year follow up.

Jian-Pi-Zhi-Dong-Decoction regulates the expression of glutamate transporters to attenuate glutamate excitotoxicity and exerts anti-tics effects in Tourette syndrome model rats.

PurposeThis study explored whether Jian-Pi-Zhi-Dong-Decoction (JPZDD) could regulate the metabolism of glutamate (GLU) and its transporters in the striatum to exert anti-tics effects in Tourette syndrome (TS) rats.Materials and methodsWe randomly assigned 56 Sprague Dawley rats into four groups, each with 14 rats: control, model, tiapride (Tia), and JPZDD. TS groups (model, Tia, and JPZDD) received intraperitoneal injection of 3,3′-iminodipropionitrile for 7 days to establish TS model. Thereafter, rats in the four groups were treated differently once a day for 6 weeks. Behavioral evaluation was performed each week by using stereotypy recording and autonomic activity test. The level of GLU in the striatum was examined by high-performance liquid chromatography. Expression of EAAT1 and VGLUT1 were measured by quantitative real-time PCR (qRT-PCR) and laser scanning confocal microscope.ResultsCompared with the model group, the stereotypy score and autonomic activity were decreased in Tia and JPZDD groups. Notably, the model group had increased concentration of GLU, which decreased after JPZDD and Tia treatments. In the model group, EAAT1 and glial cells were highly co-expressed and the relative fluorescence intensity (FI) of EAAT1 was significantly lower than that in the control group. Treatment with JPZDD and Tia increased the relative FI of EAAT1. The mRNA level of EAAT1 decreased in the model group compared to that in the control group, although it was significantly elevated following JPZDD or Tia treatment. In the model group, there was low co-expression of VGLUT1 and axon cells and the FI of VGLUT1 was remarkably increased relative to that in the control group and reduced following treatment with JPZDD and Tia. A similar trend was observed in the mRNA and protein expression of VGLUT1, although it was not statistically significant.ConclusionThe mechanism by which JPZDD alleviated behavioral dysfunction of TS rats may be associated with maintaining normal GLU transport by upregulating EAAT1 and down-regulating VGLUT1 in the striatum.

Effect of Arterial Hypertension on Postoperative Mortality and Morbidity after Off-pump CABG Surgery

Background: Arterial hypertension is one of the leading modifiable risk factor in coronary artery disease patients who underwent coronary artery bypass grafting (CABG) with the major impact on clinical outcome in these patients. This study was done to evaluate the effect of arterial hypertension on postoperative mortality and morbidity after off-pump CABG.Methods: 200 patients with mean age of 52 ± 6 years, (182 male/18 female) undergoing off pump CABG were divided equally into two groups, 100 patients with hypertension (Group A) and 100 patients without hypertension (Group B). Postoperative mortality and morbidities (Wound infection, AMI, TIA, Stroke) up to 6 months were recorded in the 2 groups.Results: In comparison with the normotensive patients, hypertensive patients had a higher mortality rate (Group A 10% and Group B 2%, p value-&lt;0.05) and increased frequency of myocardial infarction (Group A 12 % and Group B 3%, p value - &lt;0.05). There was also increased rate of infection in hypertensive patients (Group A 13 % and Group B 4%, p value - &lt;0.05). We found that hypertensive patients developed post-operative cerebrovascular complications like TIA (Group A 8 % and Group B 1%, p value - &lt;0.05) and stroke (Group A 11 % and Group B 2%, p value - &lt;0.05) more frequently than normotensive patients. Post-operative ventilator support and duration of hospital stay were almost similar in both groups.Conclusions: Among CABG patients, those with a history of hypertension have an increased frequency of post-operative complications and increased mortality.Cardiovasc. j. 2017; 10(1): 13-16

Effect of Jian-Pi-Zhi-Dong Decoction on striatal glutamate and γ-aminobutyric acid levels detected using microdialysis in a rat model of Tourette syndrome.

BackgroundJian-Pi-Zhi-Dong Decoction (JPZDD) is a dedicated treatment of Tourette syndrome (TS). The balance of neurotransmitters in the cortico-striato-pallido-thalamo-cortical network is crucial to the occurrence of TS and related to its severity. This study evaluated the effect of JPZDD on glutamate (Glu) and γ-aminobutyric acid (GABA) and their receptors in a TS rat model.Materials and methodsRats were divided into four groups (n=12 each). TS was induced in three of the groups by injecting them with 3,3′-iminodipropionitrile for 7 consecutive days. Two model groups were treated with tiapride (Tia) or JPZDD, while the control and the remaining model group were gavaged with saline. Behavior was assessed by stereotypic score and autonomic activity. Striatal Glu and GABA contents were detected using microdialysis. Expressions of N-methyl-D-aspartate receptor 1 and GABAA receptor (GABAAR) were observed using Western blot and real-time polymerase chain reaction.ResultsTia and JPZDD groups had decreased stereotypy compared with model rats; however, the JPZDD group showed a larger decrease in stereotypy than the Tia group at a 4-week time point. In a spontaneous activity test, the total distance of the JPZDD and Tia groups was significantly decreased compared with the model group. The Glu levels of the model group were higher than the control group and decreased with Tia or JPZDD treatment. The GABA level was higher in the model group than the control group. Expressions of GABAAR protein in the model group were higher than in the control group. Treatment with Tia or JPZDD reduced the expression of GABAAR protein. In the case of the mRNA expression, only Tia reduced the expression of N-methyl-D-aspartate receptor 1, compared with the model group.ConclusionJPZDD could alleviate impairments in behavior and dysfunctional signaling by downregulating GABAAR in the striatum. We suggest that this acts to maintain the balance of Glu and GABA.

Perioperative hemodynamic status in children with acquired hydrocephalia.

This article demonstrates the main features of hemodynamic parameters in children with acquired hydrocephalia, as well as the dynamics of changes in these parameters on the background of total intravenous anesthesia using sodium thiopental and inhalation anesthesia with sevoflurane on the background of ventricular-peritoneal shunting. 75 children aged 6,72±3,21 months with acquired form of hydrocephalia who underwent ventricular-peritoneal shunting were included in the study. Comparing with control group, children with acquired hydrocephalia had sighnificantly higher SV and CO (hyperkinetic variant) and decreased SVR. Based on the model of Windkessel, this change of relationships of hemodynamic parameters may be explained as follows: under moderate intracranial hypertension, when autoregulation of cerebral blood flow is extremely tense and centralization of circulation is not effective enough, the increase in cardiac output provides support of systolic components of CPP. A multifactorial analysis has shown that HR incidence increased after premedication in TIVA group by 8.6% versus 5.8% in IA group from initial value. There was no sighnificant differences between groups (р>0.05). Maximum HR performance decreased at the fourth stage: 21.6% from the initial value in TIVA group (p 0.05). In our study, a significantly greater (p<0,05) SBP, DBP and MAP findings in TIA group drop, especially at the fourth stage (MAP by 18.49% from baseline). This it is really connected with the decrease of SVR (by 30.3% from baseline). In IA group on the background of BP reduction the growth of APS by 7.2% from baseline and MAP by 4.3% from baseline at the fourth stage was detected. CO in TIVA group reduced and in IA group it increased. Moreover, in IA group more significant increase of SV was marked. This testifies to the fact that during sevoflurane anesthesia the mobilization of CO takes place, activating mechanisms of heart functions. The results demonstrate that level of experienced stress at the end of the surgery did not exceed normal findings in both groups.

Abstract T P363: Blood-Brain Barrier Damage in Vascular Risk Factor Associated White Matter Disease

Background: Vascular risk factor associated white matter disease (WMD), or leukoaraiosis, has been shown to demonstrate blood brain barrier damage (BBB) in patients with vascular dementia even when not detectable with standard clinical T1 post-contrast imaging. Purpose: We sought to study the prevalence of white matter BBB damage in a population of patients admitted to an inpatient stroke service. Methods: MRI scans of patients admitted for TIA or stroke were reviewed for evidence of confluent WMD in the centrum semiovale (CSO). To be included in the study patients must also have undergone a successful DSC image acquisition, also known as perfusion weighted image (PWI). The source images of the PWI were analyzed to generate blood-brain permeability images (BBPI) as described in a previous publication (Leigh et al, PLOS One 2012). The CSO in the first image above the lateral ventricles was used in each patient to generate BBPI measures. The pre-injection images of the PWI are T2* weighted and were therefore used to outline the area of confluent T2 signal change bilaterally. No acute strokes were present in any CSO analyzed as confirmed on DWI. The mean percent leakage (MPL) of contrast was calculated for each patient. A threshold of 2% of cerebral blood volume (CBV) was used to differentiate BBB damage from noise. Results: 20 patients were included in the study, 8 were female, with a mean age of 65 years. The diagnosis was stroke in 15 patients and TIA in 5 patients. The location of the strokes were 5 pons, 3 basil ganglia, 3 periventricular, 1 thalamus, 1 cerebellar, 1 PCA, and 1 embolic shower. Of the 20 patients, 11 stroke patients and 3 TIA patients demonstrated BBB damage. The MPL ranged from 2.1% to 23.7% with an average value of 6.9% (of CBV). The MPL was even higher for the TIA group (12.2%) than for the for the stroke group (5.4%), although this difference failed to reach significance (p=0.056) . Conclusions: In patients admitted for stroke evaluation, BBB damage in confluent WMD is common. The relevance of this finding remains unclear. However there appears to be a trend towards increased BBB damage in patients who present with events that do not localize to an acute stroke; further research should be directed at establishing the clinical implications of BBB damage in this population.

Sleep Modifications in Acute Transient Global Amnesia

Transient global amnesia (TGA) is a temporary memory loss characterized by an abrupt onset of antero-grade and retrograde amnesia, totally reversible. Since sleep plays a major role in memory consolidation, and in the storage of memory-related traces into the brain cortex, the aims of the present study were: (1) to evaluate changes in sleep macro-structure in TGA; (2) to assess modifications in sleep micro-structure in TGA, with particular reference to the arousal EEG and to cyclic alternating pattern (CAP); (3) to compare sleep parameters in TGA patients with a control group of patients with acute ischemic events ("minor stroke" or transient ischemic attack [TIA]) clinically and neuroradiologically "similar" to the TGA. TGA GROUP: 17 patients, (8 men and 9 women, 60.2 ± 12.5 years). Stroke or TIA (SoT) group: 17 patients hospitalized in the Stroke Unit for recent onset of minor stroke or TIA with hemispheric localization; healthy controls (HC) group: 17 healthy volunteers, matched for age and sex. Patients and controls underwent full-night polysomnography. In the multivariate analysis (conditions TGA, SoT, and HC) a significant effect of the condition was observed for sleep efficiency index, number of awakenings longer 1 min, REM latency, CAP time, and CAP rate. TGA and SoT differed only for CAP time and CAP rate, which were lower in the TGA group. Microstructural modification associated with tga could be consequent to: (1) hippocampal dysfunction and memory impairment; (2) impairment of arousal-related structures (in particular, cholinergic pathways); (3) emotional distress.

Abstract TP440: The Discriminant Validity of the NINDS-CSN Harmonization Neurocognitive Battery in Detecting VCI in Singaporean Patients with Ischemic Stroke and TIA

Background: An international standard for the diagnosis of Vascular Cognitive Impairment (VCI) is currently in development. We report preliminary findings of Singaporean contribution to theNINDS-Canadian Stroke Network (NINDS-CSN) neuropsychological protocol harmonization study. Purpose: We examined the discriminant validity of 3 neuropsychological protocols (60 Minute (M), 30M and 5M) by comparing cognitive performance of patients with stroke and TIA to cognitively normal controls. Methods: Patients (≥50 years old) with stroke or TIA and the controls were administered the NINDS-CSN harmonization neurocognitive battery by trained psychometricians blinded to the group status of the patients or controls. ANCOVA was conducted to compare the between group cognitive performance. ROC analyses were employed to examine the ability of the 3 protocols and the cognitive domains of the 60M protocol in discriminating patients with ischemic stroke or TIA from the controls. Results: 52 patients and 64 controls were recruited. Patients were significantly older with lower level education and more self-reported depressive symptoms than the controls (mean age 67.7±9.2 vs 62.2±6.7, p&lt;.001; years of education: 6.5±4.6 vs 11.5±4.1, p&lt;.001; Geriatric Depression Scale: 3.0±3.7 vs 1.0±1.0, p&lt;.01). Using age, education and GDS as covariates, ANCOVA showed that the performance of stroke and TIA group were significantly poorer than controls on the 5-min, 30-min and 60-min protocols (F statistics range from 7.1 to 38.7, p&lt;.01). ROC analyses showed adequate discriminatory abilities of these 3 protocols (AUCs range from 0.80 to 0.84). Executive function and memory domains of the 60M protocol were two most sensitive and specific domains in discriminating patients with stroke and TIA from the controls (AUCs: 0.87, 0.81, respectively). Conclusions: The results demonstrated preliminary evidence for the validity of the NINDS-CSN neurocognitive battery in discriminating patients with ischemic stroke and TIA from cognitively normal controls.

Inflammatory Response in the First 48 Hours of Acute Ischemic Stroke

Background : Activation of endothelial cells is an important mediator of atherothrombosis. Markers of endothelial cells such as soluble adhesion molecules can be measured in plasma and reflect the activity of the endothelium and the inflammatory system. We hypothesized that patients with acute ischemic stroke would have a dynamic change in their markers of inflammation over time, primarily reflecting the activation of endothelial cells and the immunological ability to respond to an acute brain insult. We also believed that the acute inflammatory response in the first 72 hours might affect the short and long term clinical outcome. Methods : We conducted a prospective case study of 27 patients that were admitted with acute ischemic stroke during the years 2005 - 2007. All were examined clinically using the National Institute of Health Stroke Scale [NIHSS] and a brain computed tomography (CT) scan was done in the first 24 hours. Blood was drawn for levels of E-selectin, intracellular adhesion molecule 1 (ICAM-1), and vascular cellular adhesion molecule 1 (VCAM-1) on admission and 48 hours later by ELISA methods. The blood was separated and the serum was frozen at -80 ° C until analyzed as one batch. Results : Mean blood concentrations of soluble E-selectin, intracellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured on admission and 48 hours later. Clinically there were 3 groups: 6 patients with transient ischemic attack [TIA] (58 ± 12 years old, 3 women and 3 men), 8 patients with cerebrovascular accident [CVA] without recovery (75 ± 18 years old, 4 women and 4 men), and 13 patients with CVA who recovered clinically (70 ± 13 years old, 6 women and 7 men). There was a significant increase in E-selectin levels in the second measurement (from 27.5 ± 21.6 ng/ml to 38.7 ± 19.6 ng/ml; Z = -1.997, P = 0.046) in the TIA group. An inverse correlation was found between E-selectin level and age among TIA patients on admission (r = -0.913, P = 0.011) and 48 hours later (r = -0.850, P = 0.032). A positive correlation between ICAM-1 and VCAM-1 levels was found 48 hours post admission (r = 0.436, P = 0.026). Conclusions : We have demonstrated a significant increase in E-selectin level within 48 hours among patients with TIA. In the TIA group there was an inverse correlation between age and E-selectin level. This may suggest that younger patients can protect their ischemic brain more efficiently due to a more competent immune system, and that the immune system may have an important role in ischemic brain injury. J Neurol Res. 2011;1(1):16-21 doi: https://doi.org/10.4021/jnr101e

Inflammatory Response in the First 48 Hours of Acute Ischemic Stroke

Background : Activation of endothelial cells is an important mediator of atherothrombosis. Markers of endothelial cells such as soluble adhesion molecules can be measured in plasma and reflect the activity of the endothelium and the inflammatory system. We hypothesized that patients with acute ischemic stroke would have a dynamic change in their markers of inflammation over time, primarily reflecting the activation of endothelial cells and the immunological ability to respond to an acute brain insult. We also believed that the acute inflammatory response in the first 72 hours might affect the short and long term clinical outcome. Methods : We conducted a prospective case study of 27 patients that were admitted with acute ischemic stroke during the years 2005 - 2007. All were examined clinically using the National Institute of Health Stroke Scale [NIHSS] and a brain computed tomography (CT) scan was done in the first 24 hours. Blood was drawn for levels of E-selectin, intracellular adhesion molecule 1 (ICAM-1), and vascular cellular adhesion molecule 1 (VCAM-1) on admission and 48 hours later by ELISA methods. The blood was separated and the serum was frozen at -80 ° C until analyzed as one batch. Results : Mean blood concentrations of soluble E-selectin, intracellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured on admission and 48 hours later. Clinically there were 3 groups: 6 patients with transient ischemic attack [TIA] (58 ± 12 years old, 3 women and 3 men), 8 patients with cerebrovascular accident [CVA] without recovery (75 ± 18 years old, 4 women and 4 men), and 13 patients with CVA who recovered clinically (70 ± 13 years old, 6 women and 7 men). There was a significant increase in E-selectin levels in the second measurement (from 27.5 ± 21.6 ng/ml to 38.7 ± 19.6 ng/ml; Z = -1.997, P = 0.046) in the TIA group. An inverse correlation was found between E-selectin level and age among TIA patients on admission (r = -0.913, P = 0.011) and 48 hours later (r = -0.850, P = 0.032). A positive correlation between ICAM-1 and VCAM-1 levels was found 48 hours post admission (r = 0.436, P = 0.026). Conclusions : We have demonstrated a significant increase in E-selectin level within 48 hours among patients with TIA. In the TIA group there was an inverse correlation between age and E-selectin level. This may suggest that younger patients can protect their ischemic brain more efficiently due to a more competent immune system, and that the immune system may have an important role in ischemic brain injury. doi:10.4021/jnr101e

Elevated Cholinesterase Activity in Patients with TIA and Other Thrombotic Disorders.

Abstract 2991Poster Board II-967 Background.The natural function of ACTH in blood is not well defined. However elevated plasma level was reported in patients with chronic inflammation, suggesting as one of inflammatory markers. Erythrocytes possess membrane-bound acetylcholinesterase (AChE) while plasma contains a less specific cholinesterase (ChE). We reported at a previous meeting [Blood 2008, 112(11) Abst #3849] that AChE activity of RBC-derived microparticles (RMP) is 6 times higher than those in PMP. In this study we measured plasma ACTH levels in several groups and encountered unexpectedly high plasma ChE activities in patients with TIA and other thrombosis.Methods. (i) Patient population.A series of n=108 consenting patients were recruited sequentially having various disorders For purpose of analysis, they were divided in 2 main groups: n=53 with thrombosis (TBS), F/M 27/26; and n=55 non-TBS, F/M 24/31. Thrombosis group consists of venous and arterial thrombosis including those with TIA. Non TBS group consists of anemias, thrombocytopenias including ITP, MDS. (ii) Assaywas essentially by Ellman's method. In our system, milli-absorbance units/min (mA/min) x 0.065 = umols substrate cleaved/min. Values reported here are in unitsof mA/min per mL plasma. Normal controls (NC, n=14) had a cutoff of 3000 mA/min per mL plasma, = mean +2SD. (iii) Sample handling.Platelet-poor plasma (PPP) was prepared by centrifuging 10 min at 1800 xg, then frozen in aliquots. For assay, it was diluted 1:20 with saline, then 5 uL and 10 uL were used in 96-well microtiter plate. Results:(i) Significantly higher ChE activity was observed in thrombosis (TBS) patients compared to non-TBS. Mean value ±SD in TBS was 2928 ±773, and in Non-TBS was 1897 ±713 (units as above). This difference was significant, p<0.001. (ii) When analyzed elevated levels of ACTH above 2SD of normal controls (n=26) between 2 groups, the TBS group had elevated ChE (>3000) in 30% of patients, while the Non-TBS had elevated ChE in 7.8%. (iii) Further analysis among thrombosis group revealed that the subgroup with neurological TBS (TIA, minor strokes) had the most consistent elevations of ACTH; 10 of15 with TIA group (66%) had ChE activities >3000. Summary/ Discussion.Although ChE and AChE in blood has long been studied, to our knowledge, this is the first report to show a relation between plasma ChE and thrombosis. Its elevation is very pronounce in thrombosis of the CNS, manifesting as TIA. Further study is warranted to elucidate how ChE is related to AChE of the CNS and on red cells. Disclosures:No relevant conflicts of interest to declare.

P01-22 Lorazepam, tiapride and pregabalin in alcohol withdrawal: A multicenter, randomised, comparison trial

Introduction:In this multicenter, randomised, single-blind, parellel group, comparison trial we aimed to investigate the efficacy of lorazepam, tiapride and pregabalin in alcohol withdrawal. Craving and psychiatric symptoms improvements were the secondary endpoints.Methods:One-hundred-nine alcohol dependent subjects (DSM-IV) were detoxified and subsequently randomised into three groups, respectively receiving 200-400 mg of tiapride (TIA; mean dosage 300 mg), 2-5 mg of lorazepam (LOR; mean dosage 3 mg) and 150-450 mg of pregabalin (PRE; mean dosage 280 mg). Withdrawal symptomatology was determined by the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), whereas the level of craving for alcohol was evaluated by a 10-cm Visual Analogue Scale (VAS) and the Italian -version of the Obsessive and Compulsive Drinking Scale (OCDS). Psychiatric symptomatology was evaluated by the Symptom Check List 90 Revised (SCL-90 R).Results:All the three medications have shown efficacy on reducing alcohol drinking indices, craving scores and withdrawal symptomatology. The reduction observed in the PRE group was significantly higher than those in the LOR and TIA groups. In terms of safety and tolerability, all the compounds were generally well-tolerated. Only one patient has reported an epileptic episode during the treatment with tiapride.Discussion:Results from this study globally place the three medications at the same range of efficacy, with the PRE group reporting an higher reduction of withdrawal symptoms. Another point in favour of the employment of pregabalin was represented by a better outcome in those patients reporting a comorbid psychiatric disorder.

Can Comprehensive Stroke Centers Erase the ‘Weekend Effect’?

Background: Prior epidemiological work has shown higher mortality in ischemic stroke patients admitted on weekends, which has been termed the ‘weekend effect’. Our aim was to assess stroke patient outcomes in order to determine the significance of the ‘weekend effect’ at 2 comprehensive stroke centers. Methods: Consecutive stroke patients were identified using prospective databases. Patients were categorized into 4 groups: intracerebral hemorrhage (ICH group), ischemic strokes not treated with IV t-PA (intravenous tissue plasminogen activator; IS group), acute ischemic strokes treated with IV t-PA (AIS-TPA group), and transient ischemic attack (TIA group). Weekend admission was defined as the period from Friday, 17:01, to Monday, 08:59. Patients treated beyond the 3-hour window, receiving intra-arterial therapy, or enrolled in nonobservational clinical trials were excluded. Patient demographics, NIHSS scores, and admission glucose levels were examined. Adverse events, poor functional outcome (modified Rankin scale, mRS, 3–6), and mortality were compared. Results: A total of 2,211 patients were included (1,407 site 1, 804 site 2). Thirty-six percent (800/2,211) arrived on a weekend. No significant differences were found in the ICH, IS, AIS-TPA, or TIA groups with respect to the rate of symptomatic ICH, mRS on discharge, discharge disposition, 90-day mRS, or 90-day mortality when comparing weekend and weekday groups. Using multivariate logistic regression to adjust for site, age, admission NIHSS, and blood glucose, weekend admission was not a significant independent predictive factor for in-hospital mortality in all strokes (OR = 1.10, 95% CI 0.74–1.63, p = 0.631). Conclusions: Our results suggest that comprehensive stroke centers (CSC) may ameliorate the ‘weekend effect’ in stroke patients. These results may be due to 24/7 availability of stroke specialists, advanced neuroimaging, or ongoing training and surveillance of specialized nursing care available at CSC. While encouraging, these results require confirmation in prospective studies.

Maximal Potential Patent Foramen Diameter Does Not Correlate with the Type or Frequency of the Neurologic Event prior to Closure

Background: We analyzed our data on patients undergoing transcatheter patent foramen ovale (PFO) closure to determine if the maximal potential PFO diameter (MPPD) by balloon sizing correlates with important clinical characteristics in this population. Methods: We defined stroke as a focal neurologic deficit lasting >24 h, or focal deficit of shorter duration associated with permanent MRI/CT changes consistent with a focal infarction. Parameters analyzed included age, gender, anticoagulation, hypertension, smoking, MRI/CT findings and MPPD at catheterization. We specifically analyzed the type of neurologic event (stroke/transient ischemic attack, TIA), and number of recorded preceding clinical neurologic events. Results: In 216 consecutive patients, 167 suffered a stroke. MRI/CT changes consistent with one or more embolic events were seen in 156 patients; 49 had a clinical TIA. There was no significant difference in MPPD between stroke (11.0 ± 3.6 mm) and TIA groups (10.9 ± 3.9 mm; 95% confidence interval for difference: –1.33 to 1.00). MPPD did not differ between MRI/CT-positive vs. -negative strokes, and had no correlation with the number of identified pre-closure clinical neurologic events. Conclusions: Continued investigation is needed to determine whether other PFO characteristics, or other anatomic/physiologic parameters, may be useful to identify patients at high risk for cryptogenic stroke/TIA, even before they have their first neurologic event.