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Burnout ist ein prozesshaftes Geschehen, in dessen Entstehung eine dysfunktionale Interaktion zwischen Person und auseren Belastungen (beruflich, auserberuflich) eine zentrale Rolle spielt. Es geht einher mit emotionaler und korperlicher Erschopfung, verminderter Leistungsfahigkeit und einer negativen Einstellung zum Beruf sowie anderen Belastungsfaktoren und den damit verbundenen Menschen. Im Rahmen von Burnout sind haufig depressive Storungen, Angststorungen und andere psychiatrische und psychosomatische Storungen, sowie korperliche und kognitive Storungen feststellbar. Eine Differenzierung zu anderen (v. a. psychiatrischen) Krankheitsbildern ist vor allem anhand der Anamnese eines lang dauernden (Monate, Jahre) Prozesses der Entstehung entlang auserer Belastungsfaktoren moglich. Diese Differenzierung ist essenziell fur ein adaquates, multiprofessionelles Vorgehen, in dem medikamentose Behandlung, Psychotherapie, Coaching, Lebensstilmodifikation und Verfahren der Stressreduktion differenziert und aufeinander abgestimmt einzusetzen sind.

Purpose: To relate the occurrence of incontinence due to acute ischemic stroke (AIS) by demographic factors, concomitant diseases, and severity of stroke and to investigate the associations of incontinence due to stroke with early clinical outcome within the first week after event. Materials and Methods: Of 2 659 consecutive inpatients with AIS who were admitted within 72 h of symptom onset, patients with de novo incontinence after event (n=303, m:f=131:172, age:median=74a, min=25, max=95) were analyzed in comparison to continent patients (n=1 494, m:f=877:617, age:median=67a, min=18, max=93). The occurrence of incontinence due to stroke was measured by history taking and clinical examination. The occurrence of incontinence due to stroke was analyzed in relation to concomitant diseases, medical complications occurring within the 1 st week after admission, the National Institute of Health Stroke Scale 24–36 h after admission (NIHSS), and the modified Rankin Scale at 5–7 days after admission (mRS). Results: In patients admitted due to acute stroke age (p Conclusions: In comparison to continent patients, incontinent patients had a worse functional outcome, more early vascular complications, and infections. Higher age and stroke severity may be predisposing factors for poor functional outcome.

Aim of this study Aim of this explorative study was to compare pulse palpability of lower legs arteries and early outcome within the first week after admission due to acute ischemic stroke (AIS). 2 155 patients (m:f=1 166:989; age: median=69; min=18, max=98 years, Body Mass Index: median=26.0, min=14.9, max=61.9 kg/m 2 ) with ischemic stroke and all 8 pulses checked within the first week were included in this cohort study explorative cohort study . Pulse palpability of left and right lower legs arteries was compared with medical complications within 1 week after admission, the National Institute of Health Stroke Scale 24–36 h after admission (NIHSS), and the modified Rankin Scale at 5–7 days after admission (mRS). Significant associations between increased risk for heart failure (p=0.011), urinary infection (p=0.016), ischemic stroke (p=0.030), fever (p=0.049) and bad pulse palpability were observed. The correlation between mRS and bad pulse palpability was marginally significant (r S =0.041, p=0.056). The correlation between NIHSS and bad pulse palpability was slightly higher and correlation was statistically significant (r S =0.095, p In the present study, significant correlations between bad pulse palpability of lower limb arteries and heart failure, urinary infection, ischemic stroke, fever, NIHSS, and marginally with mRS could be shown, respectively. This seems to indicate a poor early outcome of patients with “bad” pulse palpability after AIS. Pulse palpation as a simple, cost-effective, and time sparing examination, is recommended to help to prevent cardiac events in some cases after AIS.

Background: Gene variants associated with disease could reveal novel mechanisms. We searched for single nucleotide polymorphisms (SNPs) associated with noncardioembolic stroke (nonCES). Methods: We tested 24,926 SNPs in or near genes for association with nonCES in the Vienna Study (551 cases, 815 controls) and then evaluated the associated SNPs in the UCSF-CC Study (570 cases, 1,604 controls) first in pooled DNA samples and then in individual DNA samples. We then asked whether the risk alleles of the SNPs associated with increased risk in both studies were also associated with increased risk of nonCES in the German Study (728 cases, 1,041 controls). Results: Six of the 46 SNPs that were associated with nonCES in both the Vienna and the UCSF-CC Studies were also associated with nonCES in the German Study: rs362277 in HTT (OR 1.39, 90% CI 1.12–1.71), rs2924914 near CSMD1 (OR 1.22, 90% CI 1.04–1.43), rs1264352 near DDR1 (OR 1.20, 90% CI 1.02–1.41), rs544115 in NEU3 (OR 1.63, 90% CI 1.02–2.62), rs12481805 in UMODL1 (OR 1.31, 90% CI 1.01–1.81), and rs2857595 near NCR3 (OR 1.15, 90% CI 1.00–1.32). Accounting for multiple testing of 46 SNPs, these 6 SNPs had a false discovery rate of 0.69. Conclusions: Some of the 6 SNPs may be associated with nonCES but most may be false positives. These 6 SNPs merit investigation in additional nonCES study populations.

Neurohumoral effects have been suggested to affect kidney function. Stroke is a condition where regulation of the renin-angiotensin system and sympathetic nerve activity are altered.Renal function as estimated by serum creatinine was analyzed over 1 week in 220 patients after acute ischemic stroke.In patients with chronic kidney disease defined as those with serum creatinine1.2 mg/dL at admission (n = 62), renal function transiently improved, measured by a mean decrease of creatinine of 0.34 mg/dL during the first days after stroke. A significant and transient decrease of creatinine was also observed in patients with diabetes (n = 69) or patients with heart failure (n = 89). In both subgroups creatinine decreased by a mean of 0.49 and 0.24 mg/dL, respectively (p0.05 for both). In patients with normal renal function at admission, no change in serum creatinine occurred during the first week after stroke. There was no association between stroke severity and creatinine change.An acute ischemic cerebrovascular event intermittently improves impaired kidney function. The underlying mechanism may involve central regulation of renal function.

Data on long-term survival of younger patients with ischemic stroke (IS) are limited. We assessed mortality rates and clinical predictors of survival in patients with IS or transient ischemic attack (TIA)

To elucidate the relationship between excessive daytime sleepiness (EDS) in obstructive sleep apnea (OSA) and carotid atherosclerosis determined by ultrasonography and serum surrogate markers.One hundred and forty-seven patients (102 males) with snoring and sleep-disordered breathing were investigated. Carotid atherosclerosis was evaluated by serum analysis of high-sensitivity C-reactive protein and fibrinogen and four sonographic indices: intima media thickness (IMT) of the common carotid artery (CCA), IMT from the bulb to the internal carotid artery (ICA), combined IMT measurements from all segments and a plaque score. EDS was assessed by the Epworth Sleepiness Scale (ESS). Pearson correlation analysis, intergroup comparison (ANOVA) and two multiple regression models explored associations between confounders, surrogate markers and EDS.Forty-four patients had no OSA (apnea-hypopnea index AHI5h(-1)), 27 mild (5-15), 25 moderate (15-30) and 51 severe OSA (30). The ESS significantly distinguished severe OSA from non-OSA patients (p=0.003). It showed significant correlations with the BMI, HbA1c, systolic RR, the AHI, sleep time spent with an oxygen saturation90%, the respiratory arousal index, IMT of the CCA and combined IMT measurements, but no correlation with serum markers. The ESS was found to be an independent predictor of CCA-IMT in the pre-polysomnographic multiple regression model (p=0.008), but not in the post-polysomnographic model after including respiratory variables.EDS is associated with obesity, diabetes and all respiratory variables in OSA patients and may serve as an independent predictor of carotid atherosclerosis before polysomnography.

It is unclear whether prior therapy with antiplatelet agents (APA) is associated with a better outcome in patients with acute ischemic cerebrovascular events.Within a multi-center cross-sectional study, nested in a cohort we analyzed the relation between prior therapy with APA and stroke severity in 1643 patients with acute ischemic stroke or TIA. Clinical severity of the vascular event was evaluated by the National Institutes of Health Stroke Scale on admission (NIHSS1) and after 1 week (NIHSS2). By means of analysis of variance we analyzed a possible association of APA with stroke severity and interactions regarding stroke severity between APA and other clinical measures.475 patients (29 %) received aspirin prior to the cerebrovascular event, 51 patients (3 %) ticlopidine or clopidogrel and 26 patients (1.6%) aspirin combined with extended release dipyridamole. 66% (1091) of patients did not take any antiplatelet medication. Neither the NIHSS1 nor the NIHSS2 nor the change of stroke severity between these time points (NIHSS1- NIHSS2) was associated with prior APA medication. We did not find significant interactions between APA use and clinical measures regarding stroke severity.Our results do not indicate that prior therapy with APA is associated with a better outcome in acute ischemic cerebrovascular events. There were no interactions found with other features that were associated with stroke severity.

There is increasing evidence of a causal interaction between obstructive sleep apnea (OSA) and cerebrovascular disease. The aim of the study was to elucidate the relationship between the polysomnographically (PSG) measured severity of OSA and carotid atherosclerosis determined by ultrasonography and serum surrogate markers. 147 patients (102 males, 45 females) referred to our sleep laboratory for evaluation of snoring and sleep-disordered breathing were investigated. Carotid atherosclerosis was evaluated by serum analysis of high-sensitivity C-reactive protein (hs-CRP) and fibrinogen and four sonographic indices: intima-media thickness (IMT) of the common carotid artery (CCA), IMT from bulb to internal carotid artery (Bulb-ICA), combined IMT measurements from all segments and a plaque score (PlaS). Pearson correlation analysis, intergroup comparison (ANOVA), covariance analysis and a multiple regression were performed to assess the association between surrogate markers and respiratory variables. 44 patients had no OSA (apnea-hypopnea index AHI5/h), 27 mild (AHI 5-15), 25 moderate (AHI 15-30) and 51 severe OSA (AHI30). After adjusting for potential confounders, significant differences between the controls and all three OSA groups were observed in the CCA-IMT (p = 0.032) and in the PlaS between the controls and the severe group (p = 0.034). Multiple regression revealed the AHI as an independent predictor of CCA-IMT (p = 0.001) and combined IMT (p = 0.001), whereas the percentage of total sleep time with an oxygen saturation below 90 % was associated with Bulb-ICA IMT (p = 0.018) and hs-CRP (p = 0.015). OSA is associated with higher surrogate levels of cerebrovascular disease. Even mild OSA seems to predispose to early atherosclerosis.

Background: Amiloride-sensitive epithelial sodium channels (ENaCs) are important candidates in the development of hypertension, which is a major risk factor for stroke. Two single-nucleotide polymorphisms (SNPs) in the gene that encodes the ENac α-subunit (αENaC) have been identified. We evaluated those SNPs for a possible association with ischemic cerebrovascular events (ICEs). Methods and Results: We genotyped 1399 patients with ICEs [median age, 70 years; interquartile range, 58–78 years; 745 (53%) men] and 1076 control individuals without vascular disease [47 (39–58) years; 557 (52%) men] for the SNPs Trp493Arg and Ala663Thr. The SNP frequencies at nucleotide 3977 (Trp493Arg) in the αENaC gene were significantly different in patients and controls. Carriers of 493Arg had a 1.78-fold increased risk (95% confidence interval, 1.02–3.12) for ICEs compared with Trp/Trp carriers. Interaction analysis revealed that the relative risk was even higher in women in the lowest age tertile [adjusted odds ratio, 3.26 (1.10–9.72)]. Conclusions: Carriers of the 493Arg allele are at increased risk for ICEs compared with Trp/Trp carriers. The effect is independent of traditional vascular risk factors and is particularly evident in younger women. The Trp493Arg variant in αENaC may represent an important candidate genetic susceptibility factor in the development of ICEs.

BACKGROUND: Oral anticoagulation is indicated in secondary prevention of stroke or transient ischemic attack (TIA) in patients with atrial fibrillation, but it is often withheld because of contraindications and/or fear of bleeding complications. METHODS: We analysed recurrent cerebral and non-cerebral ischemic vascular events, major intracerebral and extracerebral bleeding and vascular death in 401 consecutive patients with ischemic stroke or TIA and atrial fibrillation who were discharged with oral anticoagulation (OAC), antiplatelet agents (AA), or heparin only in a clinical routine setting. The median follow-up time was 25 (interquartile range, 15–38) months. RESULTS: Patients on OAC at time of discharge were significantly younger and had suffered a major stroke less often than patients who received AA or heparin at discharge. One year after discharge, adherence to therapy was higher in patients discharged on OAC (72%) than in those on AA (46%; p < 0.001). The majority of patients discharged on heparin were subsequently treated with OAC. Patients on AA at discharge suffered from ischemic complications significantly more often during the follow-up period than patients on OAC or heparin at discharge (30% vs. 16% vs. 23%, p = 0.031). 3% of the patients on AA and 4% of those on OAC suffered from major bleeding complications during follow-up (p = 0.028). CONCLUSION: Our results document the high risk of ischemic vascular complications in patients with ischemic stroke/TIA and atrial fibrillation in a clinical routine setting. The risk was particularly high in patients treated with AA. The risk of major bleeding complications in our population was comparably low.

We performed a multicenter case-control study to evaluate the impact of the glycoprotein 1b alpha (-5)T/C Kozak polymorphism on the risk of ischemic cerebrovascular events. The genetic analysis in 1399 patients (745 men; median age, 70 years; interquartile ratio, 58-78) and 1066 control subjects (549 men; median age, 47 years; interquartile ratio, 39-59) was carried out with mutagenically separated polymerase chain reaction. Homozygous C/C genotype carriers had a 3.5-fold increased risk for ischemic cerebrovascular events (95% confidence interval, 1.5-7.9, P = 0.003) over T/T or T/C genotype carriers together. The effect was independent of well-established atherosclerotic risk factors. Our findings could be explained by the reported gene dose effect of the Kozak polymorphism on the density of the glycoprotein 1b alpha/IX/V receptors on platelets. According to our data, the (-5)C Kozak allele may represent a candidate genetic susceptibility factor for ischemic cerebrovascular events.

Heme oxygenase-1 (HO-1) has been demonstrated to exert potent anti-oxidant and anti-inflammatory effects in the context of atherosclerotic vascular disease, and therefore was referred to as a potential vascular protective factor. A (GT)n dinucleotide repeat polymorphism in the HO-1 promoter has been shown to modulate HO-1 gene expression. Short ( or =25) repeat (class L) alleles after adjustment for potentially confounding factors. Genotype distributions of S/S, S/L and L/L in patients were 9.8% (n=39), 45.1% (n=180) and 45.1% (n=180), which was similar to the distribution in controls with 11.5% (n=46), 44.5% (n=177) and 44.0% (n=175). In the presence of vascular risk factors, the HO-1 genotype became functionally relevant: in patients without hyperlipidemia the S/S genotype exerted a protective effect on the development of ischaemic cerebrovascular events (OR 0.2; 95% CI 0.1-0.6), while this effect was no longer present in hyperlipidemic patients. Short (

Background and Purpose— Magnesium (Mg) deficiency is thought to be a risk factor for cerebrovascular atherosclerosis and complications. We investigated the prognostic impact of Mg serum levels with respect to the occurrence of neurological events in patients with advanced atherosclerosis. Methods— We prospectively studied 323 patients with symptomatic peripheral artery disease and intermittent claudication (197 men; median age, 68 years). Serum Mg was determined, and patients were followed for a median of 20 months (interquartile range, 12 to 25 months) for the occurrence of neurological events, defined as ischemic stroke and/or carotid revascularization (carotid endarterectomy or carotid stenting). Multivariate Cox proportional hazards analysis was applied to assess the association of serum Mg (in tertiles) and neurological events. Results— Neurological events occurred in 35 patients (11%) (15 patients with stroke, 13 with carotid revascularization, and 7 with stroke and subsequent revascularization). Compared with patients in the highest tertile of Mg serum levels (>0.84 mmol/L), patients with Mg serum values Conclusions— Low Mg serum levels indicate an increased risk for neurological events in patients with symptomatic peripheral artery disease, favoring Mg substitution therapy in those patients with advanced atherosclerosis.

Background and Purpose— Data regarding hereditary influences on stroke remain controversial. We investigated possible associations of a family history of stroke with clinical parameters in a large cohort of well-documented patients with ischemic cerebrovascular events, with special reference to sex-specific differences. Methods— We analyzed the association between a maternal and/or paternal history of stroke and clinical parameters in 1564 patients with known maternal and paternal history of stroke and suffering from ischemic stroke or transient ischemic attack within the Vienna Stroke Registry. Results— Patients with a maternal history of stroke were significantly more often female (54%) than those without (44%; P =0.003). Hypertension was more prevalent in female patients with than in those without a maternal history of stroke (87% versus 74%; P =0.001). These associations remained significant after multivariate adjustment (adjusted odds ratio, 1.9; 95% CI, 1.1 to 3.5; P =0.024). Of those female patients with an echocardiogram (n=225), those with a maternal history of stroke more often had left ventricular hypertrophy (48%) than those without (20%) (adjusted odds ratio, 3.6; 95% CI, 1.5 to 8.2; P =0.003). In contrast, hypertension was equally prevalent in male patients with or without a maternal history of stroke (75% versus 74%; P =0.754). We found no significant associations of clinical parameters with a paternal history of stroke. Conclusions— Our results indicate a sex-specific relationship between a maternal history of stroke and the prevalence of hypertension and left ventricular hypertrophy in female patients with ischemic cerebrovascular events.

Background and purpose: Elevated plasma levels of interleukin-6 (IL-6) are associated with an increased risk and worse outcome of acute vascular events. A common G/C promoter polymorphism at nt (−174) of the IL-6 gene has been shown to affect basal IL-6 levels. Consequently, the IL-6 genotype may be associated with risk and outcome of ischemic stroke (IS). We investigated the statistical association between this polymorphism and cerebrovascular events, as well as the clinical outcome in patients with symptoms before the age of 60. Methods: We examined 214 patients of 60 years or less with acute ischemic stroke or transient ischemic attack (TIA) and 214 age- and sex-matched healthy control subjects for the (−174) IL-6 G/C polymorphism by mutagenic separated polymerase chain reaction (MS PCR). Clinical severity of the vascular event was evaluated by validated scales at predefined points of time. Results: In the total group of patients, the genotype and allele frequencies in the patient group (38% GG, 45% GC, 17% CC; allelic frequency: 60% G, 40% C) did not differ significantly from the control group. However, individuals homozygous for the (−174)G variant had significantly worse scores on the NIH Stroke Scale (NIHSS) already on admission and 1 week after the event. Also, patients with severe disability 1 week and 3 months after the event (Rankin Scale (RS) 4 or 5; NIH Stroke Scale≥6) were significantly more often carriers of the GG genotype. In a multivariate analysis, the IL-6 (−174)GG genotype was significantly associated with severe disability after 1 week (RS 4–5; odds ratio (OR)=3.2, 95% CI: 1.5–6.6; p=0.002; NIHSS≥6; OR=4.2, 95% CI: 1.6–11.1). Conclusions: The (−174)GG-genotype of the IL-6 gene is associated with severe stroke in young patients with acute cerebrovascular events. Further studies with larger patient groups are warranted to confirm these findings.

Background and Purpose— Statins reduce the risk of myocardial infarction and stroke in patients with vascular disease. Inappropriate serum lipid determination and underuse of statins have been documented in patients with coronary artery disease. Evaluation of hyperlipidemia and treatment with statins in patients with recent ischemic cerebrovascular events have not yet been investigated. Methods— We determined the frequency of total cholesterol (TC) and low-density lipoprotein cholesterol measurements and the use of statins in a multicenter prospective cohort study of 1743 patients with acute ischemic stroke or transient ischemic attack (TIA). Using multivariate logistic regression analysis, we determined the influence of several clinical variables on lipid measurements and the prescription of statins at hospital discharge. Results— TC was measured in 90% and low-density lipoprotein cholesterol was measured in 48% of the patients. Differences between the centers accounted for most of the observed variability in a multivariate model. Statin prescription also varied widely between the centers. The prescription of a statin at discharge was most strongly associated with statin intake before the event and with increasing TC levels; elderly patients received statins less often. Coronary artery disease, peripheral artery disease, and other manifestations of atherosclerosis were not independently associated with the use of statins; 68% of the patients with manifest atherosclerosis and TC levels >200 mg/dL were discharged without a statin. Conclusions— The determination of serum lipid profiles varies widely between different centers. Statins are highly underused in patients with recent ischemic stroke or TIA, particularly in those in whom statins are indicated according to existing recommendations (eg, patients with additional coronary artery disease and hypercholesterolemia). Currently, international guidelines concerning the use of statins are not adequately implemented in clinical practice in patients with stroke or TIA.

Summary. A frequent polymorphism in the factor XIII (FXIII) A-subunit gene, leading to a Val to Leu amino acid exchange at position 34, suggested to affect clot stability, has been associated with a decreased risk for venous thromboembolism and myocardial infarction. Its role in the development of stroke is still under investigation. Ninety-four patients with primary arterial intracerebral haemorrhage (mean age ± standard deviation: 69 ± 14 years; 48 men, 46 women), 718 patients with ischaemic stroke (63 ± 14 years; 395 men, 323 women) and 369 healthy control subjects (59 ± 14 years; 299 men, 170 women) were analysed for FXIII Val34Leu. No differences in genotype distribution between all three groups were observed. Also, no significant differences in the genotype distribution were found between subgroups of patients stratified according to age, sex, aetiology, history of hypertension, antiplatelet or anticoagulant medication and other vascular risk factors. In contrast to previously reported findings in smaller collectives, our data suggest that an association of the FXIII Val34Leu polymorphism with a decreased risk of ischaemic stroke or an increased risk of intracerebral haemorrhage is highly unlikely. Thus, screening for the FXIII Val34Leu polymorphism will not contribute significantly to the risk prediction of cerebrovascular disease.

Die thrombolytlsche Therapie des ischamischen Schlaganfalls wurde an den neurologischen Abteilungen in Wien im Mittel bei 3,7% der Patientinnen und Patienten eingesetzt. Die hochdosierte Gabe von Heparin ist ein unabhangiger Risikofaktor fur eine symptomatische Einblutung (OR 10,3; 95% CI 2,4–43,2) und sollte daher nur in begrundeten Einzelfallen eingesetzt werden. Patientinnen und Patienten nach TLA oder einem ischamischen Schlaganfall mit geringer Ausfallssymptomatik haben aber kein Einblutungsrisiko unter hochdosierter Gabe von Heparin. Ein Absinken des diastolischen Blutdrucks um mehr als 20 mmHg in der Akutsituation geht mit einem 3fach erhohten Risiko fur ein ungunstiges funktionelles Ergebnis einher. Komplikationen nach Schlaganfall sind haufig und treten zu 55 % innerhalb der ersten 5 Tage nach dem Ereignis auf. Die (Aspirations-Pneumonie ist ein unabhangiger Risikofaktor fur ein ungunstiges funktionelles Ergebnis nach 3 Monaten. Eine wesentliche Aufgabe der akuten Stroke Unit liegt in der Verhinderung bzw. im fruhzeitigen Erkennen und Behandeln von Komplikationen.

Objective: Recent evidence suggests that cortical activity associated with voluntary movement is relatively shifted from medial to lateral premotor areas in Parkinson's disease. This shift occurs bilaterally even for unilateral responses. It is not clear whether the shift in processing reflects an overall change in movement strategy, thereby involving alternate cortical areas, or reflects a compensatory change whereby, given the appropriate conditions, less impaired cortical areas are able to provide a similar function in compensation for those areas which are more impaired. This issue was examined in patients with hemi-Parkinson's disease, in whom basal ganglia impairment is most pronounced in one hemisphere. Methods: Fourteen patients with hemi-Parkinson's disease and 15 age-matched control subjects performed a Go/NoGo finger movement task and the contingent negative variation (CNV) was recorded from 21 scalp positions. Results and conclusions: Maximal CNV amplitudes were found over central medial regions for control subjects, but were shifted more frontally for Parkinson's disease patients, reduced in amplitude over the midline and lateralized towards the side ipsilateral to the greatest basal ganglia impairment. This shift in cortical activity from medial to lateral areas in Parkinson's disease patients appears to reflect a compensatory mechanism operating predominantly on the side of greatest basal ganglia impairment. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Contingent negative variation (CNV) was recorded from electrodes F7, F3, Fz, F4, F8, T7, C3, Cz, C4, T8, P7, P3, Pz, P4 and P8 in 19 young (mean age: 23 years) and 15 elderly (mean age: 66 years) healthy right-handed subjects, using a S2-choice paradigm. Young subjects showed early peak negativity shortly after the warning stimulus over mid-frontal areas, whereas for the remaining electrodes the negativity increased continuously. The amplitude of the early CNV was selectively reduced in elderly subjects over midline but not lateral frontal areas. We conclude that the activation of frontal midline areas as pre-supplementary motor area or anterior cingulate might be impaired in higher age.

Objective : We investigated early brain activity (under 200 ms after the stimulus onset) related to the encoding and the retrieval of verbal information. Methods : First, we compared ERPs produced by words which were encoded to ERPs produced by words from following test phases (correctly identified repetitions and correctly classified new words) in two different experiments. Experiment 1 consisted of an intentional learning paradigm and experiment 2 consisted of an incidental learning paradigm. In addition, we conducted a control experiment (experiment 3), which was a continuous recognition task with two different repetition intervals. Secondly, we conducted a magnetoencephalographic (MEG) study to further investigate early brain activity (experiment 4). The same intentional learning paradigm as in experiment 1 was used. Results : We found that ERPs elicited by correctly classified test words (repeated words and new words) of both experiment 1 and experiment 2 were significantly more negative going than the ERPs elicited by the study words. This effect was apparent between 100 ms and 200 ms after the stimulus onset and was distributed over occipital and parietal scalp locations. In the control task (experiment 3), these early potential differences were missing (for both repetition intervals). Early event-related fields (ERFs) were also found to depend on the situation of the study phase and the test phase. This activity difference peaked at 120 ms after the stimulus onset. The distributions of the difference magnetic fields were occipito-parietal and thus consistent with the findings of experiment 1 (EEG-experiment). Conclusion : Whether the effect we defined in the present study is due to an increase of activity during the test situation or due to a decrease of activity during the study situation remains unclear. However, it might reflect attentional processes within a word recognition task depending on whether a word is encoded or an effort of word retrieval has to be made.

Moderately elevated plasma homocysteine levels have been established as an independent risk factor for atherosclerosis and its complications, including cerebrovascular disease. A common mutation (C677T) in the gene encoding for the enzyme methylenetetrahydrofolate reductase (MTHFR) has been linked to increased plasma homocysteine levels in homozygous carriers, particularly in the presence of low folate levels. However, the results of most of the previous studies suggest that the C677T MTHFR mutation is not a significant risk factor for arterial disease. This discrepancy might, at least partly, be due to the fact that plasma homocysteine levels are influenced by several other factors, including age, gender, renal function, and vitamin status. We investigated the relation between plasma homocysteine levels, the C677T MTHFR mutation, and these other factors in a population of 96 patients with transient ischemic attacks or minor strokes and in 96 age- and sex-matched healthy control subjects. We further tested the value of a multivariate model for the prediction of plasma homocysteine levels under particular consideration of the MTHFR mutation status. In the patients, plasma homocysteine levels were significantly higher than in the healthy control subjects. With regard to the MTHFR mutation, the distribution of the C/C, C/T, and T/T genotypes was not significantly different between patients and healthy control subjects. Univariate (linear regression) analysis revealed significant (positive) correlations between plasma homocysteine levels on the one hand and age and creatinine on the other, the latter particularly in subjects with creatinine levels in the upper quartile. Significant (negative) correlations were found between plasma homocysteine levels, vitamin B12 , and folate levels. However, these relations could much better be expressed by means of a multiplicative regression model. T/T subjects exhibited slightly higher homocysteine levels than C/C and C/T subjects; however, the differences between the 3 genotypes were not significant. Multivariate (stepwise regression) analysis revealed age, vitamin B12 levels, folate levels, and creatinine levels as significant independent variables influencing plasma homocysteine levels, whereas the MTHFR mutation status and gender were removed from the model. Considering all 192 subjects, only 28.8% of the variance of plasma homocysteine levels could be accounted for by the model. However, in homozygous carriers of the MTHFR mutation, the predictive power of the model is very high, explaining 76.1% of the variance of plasma homocysteine levels. According to our results, the C677T mutation does not constitute a major risk factor for transient ischemic attack or minor stroke, even under consideration of other possibly confounding factors that are known to affect plasma homocysteine levels. However, it is possible to predict plasma homocysteine levels in homozygous carriers of the mutation with high accuracy. The knowledge of the MTHFR mutation status may therefore help to identify subjects at high risk for hyperhomocysteinemia. (J Lab Clin Med 1999;133:575-82)

Patients with polycythaemia vera (PV) or essential thrombocythaemia (ET) have an increased risk of arterial and venous thromboembolic complications. Since hyperhomocysteinaemia (HHC) is a risk factor for vascular disease, we investigated the frequency of HHC in these disorders and analysed a possible association of elevated plasma homocysteine levels with vascular complications. In the cohort of 134 patients from Vienna (69 female, 65 male, median age 65.5 years, range 21-91 years) with PV (n = 74) or ET (n = 60), plasma homocysteine levels were significantly higher compared to 134 healthy controls. Median homocysteine level was 12.3 micromol/l (range 3.5-48.4 micromol/l) in patients with PV or ET and 8.9 micromol/l (range 4.8-30.5 micromol/l) in normal controls (P < 0. 0001). In addition to the 134 patients from Vienna, 48 patients (28 female, 20 male; median age 66.5 years, range 24-82) from Vicenza with PV (n = 25) or ET (n = 23) were included to evaluate the impact of HHC on the risk of thrombosis. Of 59 patients with HHC (44 from Vienna and 15 from Vicenza) 18 (31%) had a history of arterial and 10 (17%) of venous thrombosis. Of 123 patients with normal homocysteine levels, 30 (24%) had arterial and 16 (13%) had venous thromboses. The difference between the two groups was statistically not significant. Even though mild to moderate HHC occurred in a larger number of patients with PV or ET and thrombosis, it can presently not be regarded as an additional risk factor for thrombosis.

A common C677T mutation in the gene for the enzyme 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR) has been linked to elevated levels of homocysteine and was therefore suspected to be a candidate genetic risk factor for arterial occlusive disease. Another mutation, factor V Leiden, has been established as a common hereditary risk factor for venous thrombosis, but its role in arterial disease remains controversial. We investigated the prevalence of both the C677T MTHFR mutation and the factor V Leiden mutation in 81 patients with transient ischemic attack (TIA) or minor stroke (MS) and in 81 age- and sex-matched control subjects free from clinically manifest vascular disease. We further compared clinical and laboratory data as well as clinical course of patients carrying the factor V Leiden mutation alone or in combination with the C677T MTHFR mutation and mutation-free patients. The prevalence of the MTHFR mutation did not differ between patients and control subjects with 11.1% homozygous carriers in both groups (OR for homozygous carriers 1.0; 95% CI 0.38-2.66). However, there was a trend towards a higher prevalence of carriers of factor V Leiden in patients (12.3%) than in control subjects (4.9%) (OR 2.75; 95% CI 0.83-9.17;p=0.09). Furthermore, we found some evidence that the combined occurrence of the C677T MTHFR mutation and factor V Leiden might unfavorably affect the clinical course of the disease, but the number of respective patients was small. Larger studies with a greater number of carriers of both the C677T MTHFR mutation and factor V Leiden seem therefore warranted.

Event-related potentials (ERPs) were recorded during a continuous recognition memory paradigm in patients with left-sided (LTLE; n = 8) or right-sided temporal lobe epilepsy (RTLE; n = 6), and in healthy control subjects (n = 24). Control subjects and both patient groups exhibited consistent OLD/NEW ERP-differences from 200-600 ms after stimulus onset. ERPs did not differ significantly between LTLE and RTLE patients, with respect to OLD/NEW distinction or the type of presented material (verbal vs. non-verbal). However, ERP topography showed significant differences between LTLE and RTLE patients: in lateral fronto-temporal recordings, patients showed larger negativities contralateral to the seizure focus, whereas we found larger negativities ipsilateral to the seizure focus in parietal recordings. Differences between the groups were significant from 300 to 600 ms post-stimulus. As a consequence, the amplitude gradient from fronto-temporal to parietal recordings was higher on the right side in LTLE patients and on the left side in RTLE patients. Again, differences between LTLE and RTLE patients were highly significant. We assume that ERPs reflect disturbances of a cortico-cortical network dependent on the side of the seizure focus in temporal lobe epilepsy. Furthermore, scalp-recorded ERPs might be a useful tool in the prediction of the side of the seizure focus in patients with temporal lobe epilepsy.

There are current attempts to replace the WADA test for pre-surgical evaluation of hemispheric language capabilities by one of the methods of functional brain imaging. Recent PET and fMRI studies using verbal cognitive tasks like verb generation, semantic monitoring or semantic ('deep') encoding of words showed asymmetries of activation in the fronto-lateral cortex. In a previous ERP study subjects were required to indicate whether pronounceable non-words and abstract geometric figures were presented for the first time ('new item') or whether they had been shown before ('old item'). Group analyses of this study showed significant material-specific hemispheric asymmetries with ERPs being more negative-going in recordings of the posterior part of the left hemisphere with verbal material (CP5/6) but more negative-going in recordings of the right hemisphere with the spatial material (P7/8). The aim of the present study was to test statistically ERP lateralization effects in individual healthy subjects as well as WADA-tested patients suffering from seizures of the mesio-temporal lobe (MTL). In all subjects ERP lateralization with verbal material was tested in the electrode pair CP5/6, and ERP lateralization with figures in the electrode pair P7/8. Statistical analyses of single trials showed that in 20 out of 24 subjects ERPs with verbal material started to be more negative-going in CP5 as compared to CP6 in the period between 100 and 200 ms after stimulus onset or the subsequent time epoch (200-300 ms). In one subject not CP5/6 but the closely adjacent electrode pair P7/P8 showed this verbal material-related hemispheric effect. In patients language dominance as indicated by ERPs was not always consistent with the data of the WADA test. In one patient with left MTL seizures ERPs with verbal material and figures were found to be significantly lateralized to the right hemisphere although the WADA test assigned this patient to have a language-dominant left hemisphere.

purpose Only few data are available concerning variations of lipids and lipoproteins in the acute stage after ischemic cerebrovascular events. It was the aim of this study to investigate whether the lipid and lipoprotein levels obtained in the first few days after a transient ischemic attack (TIA) or a minor stroke (MS) actually reflect ‘correct' values or ‘changed' (ie, false low) values, as in patients after acute myocardial infarction. patients and methods Total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and triglyceride (TG) levels of 37 unselected patients with TIA or MS were determined within 12–48 hours (Group A) or within 49–168 hours (Group B) after the acute event. After a mean observation period of 15.3 months, all patients were re-examined; the results were compared with those of the baseline evaluation. results At the time of the baseline evaluation, TC and LDL-C levels of Group B patients were significantly lower than Group A levels. At the end of the observation period, however, Group A and Group B patients did not differ with regard to all four parameters. In comparison with the baseline examination, the values of Group A patients had not changed. In Group B patients, however, TC, HDL-C, LDL-C, and TG levels had significantly increased. conclusion Our results strongly suggest that lipid and lipoprotein levels of patients with TIA or MS should be assessed within a maximum of 48 hours after the acute event. If the examination cannot be performed within that period, the determination of reliable values is possible only after several weeks or months.

The total of free and protein-bound homocysteine including its derivatives is usually summarised as "homocyst(e)ine [H(e)]". Several congenital enzyme deficiencies may cause markedly elevated H(e) plasma levels, leading to the well-known clinical syndromes of homocystinuria. Recently, mild hyperhomocyst(e)inemia has been recognised as an independent risk factor for ischaemic cerebrovascular disease, coronary heart disease, and peripheral artery disease. H(e) levels are also related to the extent of atherosclerotic vessel wall alterations. The role of mild hyperhomocyst(e)inemia in venous thromboembolic disease, however, is not yet clear. A considerable proportion of patients with mild hyperhomocyst(e)inemia suffers from a deficiency of folate, vitamin B12, and/or vitamin B6. Supplementation of these agents--alone or combined with betain--leads to a decrease or even to a normalisation of elevated H(e) levels in the majority of such patients. Hitherto, no prospective randomised studies dealing with the clinical efficacy of such a--probably innocuous--supplementation have been performed. In the meantime, adequate alimentary intake of folate should be ensured.

Recently, a C--T polymorphism at nucleotide 46 in the 5'-untranslated region of the factor XII (FXII) gene was shown to be associated with lower levels of FXII. To study the impact of this polymorphism on the development of an acute coronary syndrome (ACS), we compared 303 patients with ACS and 227 patients with stable coronary artery disease (CAD). In the latter group, 54.2% of individuals carried wild-type FXII:46C, 37.9% were heterozygous FXII:C46T and 7.9% were homozygous for FXII:46T. In contrast, in the ACS group (n = 303), 54.1% were wild-type FXII:46C, 42.6% were heterozygous FXII:C46T and only 3.3% carried the homozygous FXII:46T genotype. The 2.5-fold lower prevalence of the FXII:46T genotype in patients with ACS could indicate a protective effect on the development of ACS (odds ratio = 0.4, 95% CI 0.1-0.9) in patients with pre-existing CAD.

Frage: Ziel der vorliegenden Studie war die Untersuchung von Zusammenhangen zwischen einer relativ rezenten, „starken“ Gewichtsabnahme (mehr als 4kg) innerhalb des letzten halben Jahres vor einem ischamischen Schlaganfall und dem „Outcome“ innerhalb der ersten Woche nach dem Insult. Methode: Diese Untersuchung wurde im Rahmen der Wiener Schlaganfalldatenbank durchgefuhrt. Insgesamt konnten hierbei 2659 Patienten (m:f=1421:1238; Alter: median=70, min=18, max=98 a; BMI: median=26, min=14, max=62kg/m2) mit ischamischem Schlaganfall identifiziert werden. Zu den relevanten Begleiterkrankungen zahlten in der Wiener Schlaganfalldatenbank-Studienpopulation die Hypertonie (n=1691, 64%), Schlaganfall in der Anamnese (n=483, 19%), Koronare Herzerkrankung (n=609, 24%), Diabetes mellitus (n=646, 25%), Periphere Arterielle Verschluss-Krankheit (n=275, 12%), Herzinsuffizienz (n=717, 28%), davon gravierende Herzinsuffizienz (n=208, 8%), Malignome (n=131, 5%), Lungenerkrankungen (n=284, 11%), davon gravierende Lungenerkrankungen (n=106, 4%) und Demenz (n=43, 2%). In der vorliegenden Untersuchung wurden alle in die Wiener Schlaganfalldatenbank eingeschlossenen Patienten mit ischamischem Insult sowie suffizienter Dokumentation der fur die Fragestellung erforderlichen Parameter analysiert. Die definitionsgemas (mehr als 4kg) starke Gewichtsabnahme wurde mit den innerhalb der ersten Woche nach Schlaganfall auftretenden Komplikationen sowie der „National Institute of Health Stroke Scale“ 24 bis 36 Stunden nach dem Ereignis (NIHSS 24–36h) bzw. der modifizierten „Rankin Scale“ 5–7 Tage nach Ereignis (RS 5–7D) statistisch (Chi2-Test bzw. Wilcoxon Rangsummentest) miteinander verglichen. Ergebnis: Von den eingeschlossenen 2334 Patienten (m:f=1247:1087) verloren 175 Patienten (BMI: median=29, IQ=26, UQ=32kg/m2) absichtlich und 195 Patienten (BMI: median: 26kg/m2, IQ=24, UQ=29kg/m2) unabsichtlich innerhalb des definierten Zeitraumes mehr als 4kg Korpergewicht. Von einer nicht beabsichtigten starken Gewichtsabnahme waren erwartungsgemas Patienten mit bestimmten Vorerkrankungen (Malignome, Herzinsuffizienz und Demenz) signifikant haufiger betroffen (p=0,0427, p=0,0062 bzw. p

SummaryOverexpression of plasma cell membrane glycoprotein-1 (PC-1) inhibits insulin receptor tyrosine kinase activity and thus favours insulin resistance and atherosclerotic vascular disease. Recent findings indicate that the minor variant K121Q in the PC-1 gene confers an increased risk for early myocardial infarction independent of other established risk factors. We hypothesized that genetic variants in PC-1 may also influence the risk for cerebrovascular disease.Therefore, we assessed the association of the PC-1 K121Q variant in the coding region and a polymorphism (G2906C) in the 3’ untranslated region of the PC-1 gene with the risk of stroke.We analyzed 1014 patients with a history of ischaemic stroke from the Vienna stroke registry and 1001 control individuals without vascular disease.Genotype frequencies of both genetic variants were similar in patients and controls in the total study population. By multivariate analysis, no interactions were observed between the PC-1 genotype and established vascular risk factors. However, the PC-1 2906C allele was significantly more frequent in patients who suffered from stroke before the age of 40 years. In these patients the risk for ischaemic stroke was increased fourfold.

Noncardioembolic stroke and coronary heart disease (CHD) may share genetic predispositions. We tested the hypothesis that genetic variants which are associated with risk of CHD would also be associated with risk of noncardioembolic stroke in 562 cases from the Vienna Stroke Registry and 815 controls. We selected 6 gene variants that had been consistently associated with risk of CHD in 3 studies, including the Atherosclerosis Risk in Communities study, and found that 4 of these gene variants were also associated with risk of noncardioembolic stroke. The odds ratios for noncardioembolic stroke were 1.31 (90% CI 1.07–1.60) for rs3900940 in MYH15, 1.24 (90% CI 1.01–1.5) for rs20455 in KIF6, 1.21 (90% CI 0.99–1.49) for rs1010 in VAMP8, and 1.20 (90% CI 0.95–1.50) for rs10757274 on chromosome 9p21.

Background: Single-nucleotide polymorphisms (SNPs) in inflammation-related genes have been linked to an increased risk of ischemic stroke. Most of these SNP results have not been replicated, however, and metaanalyses of the effects of inflammation-related genes are rare. We investigated 49 SNPs in 34 genes previously reported to be related to inflammation in our study. We tested 459 patients with acute ischemic stroke or transient ischemic attack and 459 controls individually matched by sex and age. Methods: We studied genetic variation by PCR analysis and subsequent hybridization to linear arrays of sequence-specific oligonucleotides. We used univariate conditional logistic regression analysis to test for associations of conventional vascular risk factors and the SNPs with stroke. Variables showing significant differences (P < 0.05) between cases and controls were included in a multivariate model. ROC curves were plotted to assess the contribution of genetic variation to stroke risk in addition to that of conventional risk factors. Results: Univariate regression analysis revealed 3 SNPs with significant allelic differences between patients and controls, which fulfilled the criteria for further analysis. Only one of these SNPs, the C5 (complement component 5) 2416A>G variant (rs17611), remained significant after the multivariate analysis (odds ratio, 0.585; P = 0.0037). ROC curve analysis revealed no contribution of this genetic variation to stroke risk. Conclusions: We found evidence for an association of the 2416A>G polymorphism in the C5 gene with the risk for ischemic stroke. Our data suggest that the C5 gene particularly influences the risk for patients with microangiopathy.

Aim: The aim of the present study was the evaluation of actigraphy as a tool to objectify the recovery process after motor paresis due to stroke. Methods: The motor activity of both arms of patients suffering from stroke was actigraphically recorded at four different time points during the course of rehabilitation: 24–36 h, 5–7 days, 3 months, and 6 months after stroke. Results: Motor activity monitored by wrist-worn actigraphs located at the impaired side revealed an increase in activity between the first two time points and the subsequent ones. Additionally, actigraphic recordings showed lower total motor activity at the impaired side as compared to the nonimpaired side. A significant positive correlation was found between the actigraphically recorded motor activity and the results of the Scandinavian Stroke scale, the Barthel Index, the Rankin Scale Score and with the Motoricity Index during the 1st week, which corresponds to the time when neurological deficits were most pronounced. Conclusion: Our results suggest that actigraphy is a useful tool in the objective evaluation of motor activity after stroke. Moreover, actigraphy covers additional aspects that are not reflected by the usual stroke scales in a clinical situation.

Data concerning genetic factors that may influence the risk of primary intracerebral hemorrhage (PICH) are scarce. One previous study, indicated that the carriers of the (-323)Ins allele of the coagulation factor VII (FVII) have an increased risk of PICH. Another recent study, tested the effect of apolipoprotein E. We analyzed, whether the (-401)G --> T polymorphism, which is in linkage disequilibrium (LD) with the 10-bp Ins/Del polymorphism at position (-323), or the (-402)G --> A polymorphisms of the FVII gene are associated with an increased risk for PICH. We performed a small case-control study in 85 patients with PICH and in 85 healthy control subjects. To each patient a control was individually matched for age, gender, and hypertension. We did not find any significant differences in allele frequencies for the A allele of the FVII (-402)G --> A polymorphism (0.25 vs. 0.25; P = 0.900, OR = 1, ns.) nor for the T Allele of the FVII (-401)G --> T polymorphism (0.09 vs. 0.12; P = 0.480, OR = 1.38, ns.). The analysis of haplotype distributions did not reveal significant differences. Our results do not support the hypothesis that the investigated polymorphisms in the FVII gene are significantly associated with the risk for PICH.

Background and Purpose— Knowledge about hypertension and its control influences blood pressure control in patients with hypertension. We assessed these parameters in a large cohort of patients with ischemic stroke or transient ischemic attack and analyzed their association with educational attainment. Methods— Five hundred ninety-one consecutive patients with stroke with a medical history of hypertension were interviewed about knowledge concerning hypertension within a multicenter hospital-based stroke registry. We analyzed answers in relation to educational level with multivariate logistic regression adjusted for age and sex. Results— Seventy-seven percent of the patients stated to have known about hypertension being a risk factor for stroke, but only 30% felt at increased risk of stroke. Less than half (47%) could identify 140 mm Hg or less as the maximum tolerated systolic blood pressure, and 53% had their blood pressure only controlled monthly or less often. Knowledge of possible consequences of myocardial infarction, nephropathy, peripheral vascular disease, and retinopathy was 64%, 20%, 11%, and 16%, respectively. Approximately half of patients were acquainted with the nonpharmacologic treatment options of physical activity (49%), reduction of salt intake (54%), and reduction of caloric intake (48%), whereas relaxation techniques were only known to 17%. Adherence to those treatment options ranged from 42% to 67%. Educational level was significantly associated with knowledge of increased risk, possible consequences of hypertension, and knowledge about nonmedication treatment options. Conclusion— Knowledge in our population was insufficient and partly associated with educational level, leaving much room for improvement by educational campaigns. Furthermore, we found a gap between knowledge of the increased risk for stroke in patients with hypertension and awareness of their own risk.

Background: Epidemiological studies indicate that genetic factors play a role in the risk of stroke, particularly in younger individuals, but the role of single-nucleotide polymorphisms (SNPs) is controversial. We tested the possible association of a number of previously described SNPs with stroke risk. Methods: We investigated the prevalence of 60 polymorphisms located in 35 genes in 450 white patients who suffered an acute stroke or transient ischemic attack before the age of 60 years and in 817 healthy control individuals by a multilocus PCR-based assay. The controls were randomly selected from attendees of a health service program. Genetic variations were detected by hybridization to nylon strips (Roche Molecular Systems) containing detection oligonucleotides for the SNPs. We used P values of Results: Frequencies of all 60 tested SNPs among patients and controls were very similar. No SNP reached an odds ratio of 2, and no association with stroke risk was statistically significant. Conclusions: Our results do not indicate a clinically relevant role of any of the investigated SNPs for stroke risk in individuals hospitalized for ischemic stroke/transient ischemic attack before or at 60 years of age. These results are in accordance with previous metaanalyses showing at most a very modest or no significant effect of these SNPs on stroke risk.

Background and Purpose— A Thr>Pro polymorphism at codon 715 in the coding region of the P-selectin gene has recently been described. Individuals carrying the Pro715 allele were reported to have a reduced risk of myocardial infarction. A possible association of this polymorphism with the risk of ischemic stroke is currently under discussion. Methods— We investigated the prevalence of the 715 Thr>Pro polymorphism in 450 patients aged younger than 60 years with ischemic stroke or transient ischemic attack and in 450 controls without vascular disease matched for age and gender. We also investigated possible interactions of the polymorphism with other vascular risk factors, stroke severity and stroke etiology. Results— The distribution of the two allelic variants of the 715Thr>Pro polymorphism did not differ significantly between patients and control subjects (78% versus 81% for Thr/Thr, 21% versus 18% for Thr/Pro and 1% versus 1% for Pro/Pro in patients and controls, respectively; adjusted odds ratio for carriers of the C allele: 1.0 [0.8 to 1.2; P =0.695]). We found no significant interaction of this polymorphism with vascular risk factors, stroke severity, or stroke etiology. Conclusions— Our study supports results from previous investigation showing that the 715Thr>Pro polymorphism of the P-selectin gene was not associated with a risk or clinical characteristics of ischemic stroke.

Background: Coagulation factor VII (FVII) plays an important role in the activation of blood coagulation and clot formation. Recent studies have provided evidence for an association between common polymorphic markers in the FVII gene and plasma FVII concentrations. The 353R>Q sequence variation, and 3 common sequence variations in the promoter of the FVII gene—the 10-bp insertion/deletion at position −323 and the −401G>T and −402G>A sequence variations—are well-known determinants of circulating FVII concentrations. Methods: To clarify the role of these sequence variations in the pathogenesis of ischemic stroke, we performed a case–control study with 242 patients with ischemic stroke before the age of 60 years and 239 healthy controls. Results: The −323 insertion/deletion and the 353R>Q and −401G>T sequence variations were in strong linkage disequilibrium, and the resulting haplotypes occurred with equal frequencies in patients and controls. The variant form of FVII (−402G>A) occurred only in combination with the common (wild-type) sequences at all other loci. This haplotype was more frequent in patients than in healthy controls (28% vs 22%). The difference in the prevalence of carriers of this haplotype among patients and controls was statistically significant (P = 0.03; odds ratio = 1.6; 95% confidence interval, 1.1–2.6). Conclusion: According to our results, the FVII −402A allele seems to increase the risk of early ischemic cerebrovascular events, whereas the 353R>Q, G−401T, and −323ins/del sequence variations, which are in close linkage disequilibrium, apparently do not influence the risk of stroke.

BACKGROUND Chronic and acute infections are associated with an increased risk of stroke. The inflammatory response can be influenced by functional polymorphisms in components of the immune system. We hypothesized that these polymorphisms may also modulate the risk of ischemic cerebrovascular events. METHODS We determined the frequency of polymorphisms in tumor necrosis factor-alpha[(TNF-alpha) G(-376)A, G(-244)A, G(-238)A, G(-308)A], Toll-like receptor 4 [(TLR4) Gly299Asp and Thr399Ile], interleukin-1-receptor antagonist [(IL-1-RA) intron 2 variable-number tandem repeat], monocyte differentiation antigen CD14 receptor C(-260)T, and interleukin-6 [(IL-6) G(-174)C] genes in 404 patients with acute stroke or transient ischemic attack before the age of 60 years and in 415 healthy individuals. We also tested for interactions between genotypes, recent febrile episodes and stroke risk. RESULTS None of the polymorphisms was associated with an increased risk of stroke after adjustment for age and gender. Following multivariate adjustment, carriers of the TNF-alpha (-308)A allele, the IL-1-RA 2* allele or the IL-6 (-174)C allele appeared to have an increased risk of stroke in association with a febrile episode prior to strokes. CONCLUSION In our study none of the investigated polymorphisms of the inflammatory system was associated with the risk of acute cerebrovascular events before the age of 60 years. However, post-hoc analyses indicate that some polymorphisms seem to contribute to the risk of stroke in combination with fever.

ObjectivesWe investigated the effect of myeloperoxidase (MPO) on progression of carotid stenosis in states of high and low high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) levels.BackgroundMyeloperoxidase is pivotally involved in the pathogenesis of atherosclerosis. In vitro data suggest that MPO exerts deleterious effects via oxidative modulation of lipoproteins.MethodsWe prospectively studied 1,019 of 1,268 consecutive patients who were asymptomatic with respect to carotid artery disease. Patients underwent serial carotid ultrasound investigations at baseline and after a follow-up interval of median 7.5 months (range 6 to 9 months), categorizing carotid arteries as 0% to 29%, 30% to 49%, 50% to 69%, 70% to 89%, or 90% to 99% stenosed or occluded. The MPO, HDL-C, and LDL-C levels were measured at baseline, grouped by medians, and correlated with progression of carotid atherosclerosis.ResultsProgression of carotid atherosclerosis was found in 100 of 1,019 patients (9.8%). Myeloperoxidase (p = 0.014) but not HDL-C (p = 0.95) or LDL-C (p = 0.30) were associated with progressive disease. However, MPO ≥310 ng/ml was significantly associated with progressive disease (adjusted odds ratio [OR] 2.57, 95% confidence interval [CI] 1.39 to 4.75) only in patients with HDL-C levels

Percutaneous transluminal angioplasty with stenting (PTAS) has become a treatment option for severe carotid stenosis. The goal of our study was to determine prospectively neurocognitive outcome 6 months after unilateral stent-protected carotid angioplasty. Twenty consecutive patients who underwent stent-protected angioplasty for symptomatic (n=9) or asymptomatic (n=11) high-grade carotid stenosis were investigated and compared to an age and disease matched control group. Patients were administered preprocedurally and 6 months postprocedurally a battery of neuropsychological tests. We used reliable change indices methodology in order to control for practice and statistical effects unrelated to intervention. We found no cognitive change in approximately 90% of patients and cognitive improvement in approximately 10% of patients for concentration and attention variables. We further found no cognitive change in 61% of patients, cognitive improvement in 11% of patients and cognitive deterioration in 28% of patients for psychomotor speed. No cognitive change in 94% of patients and cognitive deterioration in 6% of patients was found for sustained attention; no cognitive change in 80% of patients, cognitive improvement in 15% of patients and cognitive deterioration in 5% of patients was found for verbal fluency; no cognitive change in 100% of patients was found for interference (Stroop test): no cognitive change in 95% of patients, cognitive improvement in 5% of patients was found for interference (c.I. test), respectively. Our study showed that 6 months after PTAS cognitive functioning did not change in most patients significantly. For some patients, however, significant improvement or deterioration in single neurocognitive domains can be expected. The reasons for these changes are unclear but may depend on variable type; magnitude of microemboli production; right vs. left cerebral vasculature, respectively.

Ischemic stroke is a multifactorial disease and a major cause of death and disability throughout the world. Acquired risk factors (e.g., hypertension, cigarette smoking, and diabetes mellitus) account only for ∼69% of the population-attributable risk. Thus, it is likely that other, as yet unidentified, factors contribute to the development of stroke (1). Both epidemiologic and animal-based studies suggest that alterations in a variety of candidate genes, including hemostatic genes, genes controlling homocysteine metabolism, the gene that encodes angiotensin-converting enzyme, and the gene that encodes endothelial nitric oxide synthase, are important in the pathogenesis of ischemic stroke (2)(3). Apparently the genetic influences are polygenic. In addition, ischemic stroke comprises many different phenotypes. According to previous studies, genetic factors seem to have different effects depending on stroke etiology [e.g., lacunar stroke and polymorphisms in the gene encoding interleukin-6 (4)]. In combination with acquired risk factors such as smoking, the presence of one or a combination of several predisposing genes may favor the occurrence of stroke. Cytochrome P-450 (CYP) 2C9 belongs to a large family of heme-containing enzymes that catalyze the oxidation of various drugs and endogenous substrates. CYP2C9 is produced in the liver, is responsible for 50% of the epoxygenase activity in the human liver, and metabolizes a wide variety of clinically important drugs (5). Interestingly, CYP2C isoforms also seem to play a role in the regulation of vascular tone. CYP2C9 is expressed in the endothelium and, via production of endothelium-derived hyperpolarizing factor (EDHF), may cause vasorelaxation as a result of hyperpolarization of vascular smooth muscle cells by activation of Ca2+-activated K+ channels (6). EDHF production seems to be inhibited by NO and/or prostacyclin and has been described as an important regulator of vascular tone under certain pathologic conditions and in certain vascular beds, such as …