Search

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: 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.

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.

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.

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.

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.

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 …

Background— Compelling evidence suggests that inflammation is fundamentally involved in the pathogenesis of atherosclerosis; however, temporal correlation between inflammation and morphological features of atherosclerosis progression has not been demonstrated unequivocally. Methods and Results— We prospectively studied 1268 consecutive patients who were initially asymptomatic with respect to carotid artery disease. Patients underwent serial carotid ultrasound investigations at baseline and after a follow-up interval of a median of 7.5 months (range 6 to 9 months), with measurement of carotid flow velocities and categorization of carotid arteries as 0% to 29%, 30% to 49%, 50% to 69%, 70% to 89%, or 90% to 99% stenosed or occluded. High-sensitivity C-reactive protein (hs-CRP) and serum amyloid A (SAA) were measured at baseline and follow-up. Progression of carotid atherosclerosis was found in 103 (8.1%) of 1268 patients. Hs-CRP and SAA, respectively, at baseline ( P =0.004 and P =0.014) and follow-up ( P P P P Conclusions— These findings supply evidence for a close temporal correlation between inflammation and morphological features of rapidly progressive carotid atherosclerosis, which suggests that elevation or increase of the inflammatory biomarkers hs-CRP and SAA identifies the presence of active atherosclerotic disease.

To report a propensity score-adjusted analysis of the long-term risks for stroke after carotid artery stenting (CAS) compared to medical therapy in patients with asymptomatic high-grade carotid artery stenosis.A total of 946 consecutive patients (605 men; median age 73 years) with asymptomatic high-grade carotid artery stenoses (or =70%) identified in a single center registry were treated either medically (n=525) or with CAS (n=421). A propensity score-adjusted analysis was performed to test the hypothesis that long-term neurological outcome might be better after CAS than after medical treatment, depending on the baseline degree of carotid stenosis and the patient's medical status. Baseline degree of stenosis was classified as 70% to 79% (n=307), 80% to 89% (n=366), and 90% to 99% (n=272) by duplex ultrasound. Surgical risk was estimated by the American Society of Anesthesiologists (ASA) score (I to IV).Stroke-free survival rates at 1, 3, and 5 years were 97%, 93%, and 89% after conservative treatment versus 94%, 93%, and 91% after CAS (p=0.56), respectively. Compared to conservatively treated patients with 70% to 79% stenoses, the adjusted hazard ratios for stroke were 2.36 (p=0.044) for conservatively treated patients with 80% to 89% and 3.17 (p=0.026) for those with 90% to 99% stenoses. For CAS patients with 70% to 79%, 80% to 89%, and 90% to 99% stenoses, the adjusted hazard ratios for stroke were 1.32 (p=0.63), 0.91 (p=0.84), and 0.98 (p=0.98) irrespective of the ASA score, the propensity to undergo CAS, and other potential confounders. Thus, the risk of stroke increased in parallel with the degree of stenosis in conservatively treated patients, but remained unchanged in patients undergoing CAS.Patients with asymptomatic severe carotid narrowing (or =80%) might benefit from CAS with respect to stroke-free survival. Randomized controlled trials are needed to confirm these findings.

Background and Purpose— Headache is a common symptom in acute ischemic and hemorrhagic stroke, but many aspects of its association with other clinical factors are controversial. Methods— We analyzed characteristics of headache symptoms at stroke onset and associations between headache at stroke onset and at several clinical parameters in 2196 patients experiencing ischemic stroke or transient ischemic attack within a multicenter hospital-based stroke registry. Results— Five hundred eighty-eight (27%) patients experienced headache at stroke onset. In a multivariate analysis, headache at stroke onset was positively associated with female sex, history of migraine, younger age, cerebellar stroke (but not with other brain stem locations), and blood pressure values on admission Conclusions— Our results, derived from a large number of systematically documented patients with acute ischemic cerebrovascular events, show no association of headache with stroke etiology or outcome. Our results indicate that the previously described association of headache with vertebrobasilar stroke is mainly because of its association with cerebellar stroke. We could confirm previously described associations of headache at stroke onset with younger age and a history of migraine, implicating a careful evaluation of young patients with a focal neurological deficit and a history of migraine to avoid misclassification as “complicated migraine.”

Background and Purpose— Low socioeconomic status is associated with increased morbidity and mortality from stroke. The purpose of this study was to investigate the association between 4 independent measures of socioeconomic status and mortality of patients with acute ischemic stroke and transient ischemic attack. Methods— Socioeconomic status was assessed by taking into account levels of education, occupation, occupational status, and income. The end point was overall mortality. We used Cox proportional hazard models to adjust for age, sex, and severity of stroke on admission. Results— A total of 2606 stroke patients were followed up for a median of 2.5 years. Unskilled workers had a hazard ratio of 1.87 for death after stroke (95% CI, 1.37 to 2.55) and skilled workers had a hazard ratio of 1.61 (95% CI, 1.23 to 2.11) compared with white-collar workers. Of 4 income groups, patients with the second lowest level of income had a hazard ratio of 1.60 (95% CI, 1.10 to 2.33) and patients with the third lowest level of income had a hazard ratio of 1.71 (95% CI, 1.25 to 2.32) compared with patients with the highest income. The hazard ratio for death after stroke for early retired patients was 1.75 (95% CI, 1.01 to 3.04) compared with stroke patients in the active workforce at the time of the event. Conclusions— Socioeconomic status is associated with survival of patients with acute stroke after adjustment for age, sex, and severity of stroke. The influence of socioeconomic status seems to continue to affect the outcome largely independent of stroke severity.

Background and Purpose— Increased mean platelet volume (MPV), indicating higher platelet reactivity, is associated with an increased risk of myocardial infarction. Higher levels of MPV have been found in patients with acute ischemic stroke than in control subjects. Data from smaller studies regarding an association between MPV and stroke severity and outcome have been controversial. If such an association exists, MPV might help to identify patients at increased risk of a severe course of acute cerebrovascular disease. Methods— Within a multicenter, cross-sectional study nested in a cohort, we analyzed the relation between MPV and stroke severity as determined by the modified Rankin Scale after 1 week in 776 patients with acute ischemic stroke or transient ischemic attack. By multivariate logistic regression modeling, we determined the influence of MPV on stroke severity, adjusting for potential confounding factors. Results— Patients within the highest quintile of MPV had a significantly higher risk of suffering a severe stroke, defined as modified Rankin Scale score of 3 to 6, compared with patients within the lowest quintile (odds ratio=2.6; 95% confidence interval, 1.6 to 4.1; P P =0.013). Conclusions— Our results indicate that an elevated MPV is associated with a worse outcome for acute ischemic cerebrovascular events independent of other clinical parameters.

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 (25) GT repeats were associated with HO-1 up-regulation, and therefore may influence susceptibility to ischaemic vascular events. We investigated the association of HO-1 repeat length with the risk of cerebrovascular events in a case control study and assessed possible interrelations with vascular risk factors. We determined the number of GT repeats in the HO-1 promoter in 399 patients with ischaemic cerebrovascular events and 398 healthy controls and compared the frequencies of short (25) repeat (class S) and long (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 (25 GT) repeats in the HO-1 gene promoter confer a reduced risk for cerebrovascular events in individuals with normal plasma lipid levels. This may explain controversial findings in different populations.

Study objective The relation between course of blood pressure within the first 24 hours after acute stroke and early neurologic outcome remains a matter of dispute. We investigate this relation with adjustment for other influencing variables. Methods Three hundred seventy-two patients with the diagnosis of ischemic stroke were included to evaluate the relation between blood pressure course and early neurologic outcome. The following data were collected: age; sex; history of hypertension, diabetes mellitus, hyperlipidemia, coronary heart disease, peripheral vascular disease, and stroke; smoking habits; preadmission blood pressure, blood pressure on admission, and blood pressure 24 hours later; antihypertensive treatment; and stroke localization. We assessed outcome at day 5 after admission as dependent or independent (Rankin Scale score ≤2) and applied multivariate logistic regression analysis to investigate the effect of blood pressure changes on outcome, with adjustment for other baseline variables. Results Relative changes of systolic and diastolic blood pressure within hospital admission to 24 hours after admission revealed significant differences of patients' neurologic outcome only for diastolic blood pressure changes from admission to 24 hours. A diastolic blood pressure decrease more than 25% from admission until 24 hours after admission was associated with a 3.8-fold increased adjusted odds (95% confidence interval 1.2 to 12.1) for poor neurologic outcome on day 5 (Rankin Scale score 3 to 5). Conclusion Excessive diastolic blood pressure reduction was associated with an increased risk for an impaired neurologic outcome in patients with ischemic stroke. The association between both characteristics was independent from concomitant risk factors, stroke localization, and possible antihypertensive treatment.

Although transcatheter closure of patent foramen ovale (PFO) and atrial septal defect (ASD) has become a commonly performed intervention, the incidence of cerebral embolism with or without neurological deficits during such procedures has not been studied.We monitored the middle cerebral artery in two different depths (48 mm and 53 mm) by continuous transcranial Doppler ultrasound during transcatheter PFO closure in 35 consecutive patients (F/M 20/15, mean age 47 +/- 11 years) and during ASD closure in 8 patients (F/M 7/1, mean age 45 +/- 5 years). All automatically detected high intensity transient signals (HITS) were manually reviewed to eliminate artifacts.HITS were detected in 33 of 35 patients (96%) with a median rate of 8 (interquartile range 4-19, range 2-29) HITS. The highest rates were observed when the septum was crossed with the guide wire (median 2; IQR 0-12; range 0-25) and when the left atrial disc was deployed (median 2; IQR 1-4; range 0-13). Despite this high rate of cerebral microembolism no clinically apparent neurological or neuropsychological deficit was observed.Silent cerebral embolism frequently occurs during transcatheter PFO and ASD closure. The peak of HITS at the time of crossing the septum with the guide wire may support the hypothesis that cerebral emboli in patients with PFO may originate from the septum itself. This may represent an alternative mechanism to the generally assumed paradoxical embolism.

Objective : Treatment with statins reduces the risk of ischemic stroke among patients at increased risk for vascular disease. Recent experimental data suggest neuroprotective properties of statins in acute cerebral ischemia. We investigated whether a premedication with statins is associated with a better outcome in patients with acute ischemic cerebrovascular events. Methods : Within a cross-sectional study, nested in a cohort we identified 1691 patients with a recent ischemic stroke or transient ischemic attack. Clinical severity of the vascular event was evaluated by the modified Rankin Scale (mRS) after 1 week. By means of multivariate logistic regression modeling, we determined the influence of prior statin use on stroke severity with adjustment for potential confounding factors. Results : Severe stroke, defined as a modified Rankin Scale of 5 or 6 ( n =231; 14%), was less frequent in patients receiving statin treatment before the event (6% vs. 14%, OR=0.37; 95% CI 0.19 to 0.74; p =0.004). This association remained significant after adjustment for confounding factors. We found a significant interaction between the presence of diabetes and the effect of pretreatment with statins on stroke outcome. Of the patients with diabetes, none of those on statin treatment but 16% of those without a statin had a bad outcome. After exclusion of the group of diabetic patients with prior statin medication, the protective effect was reduced and not statistically significant anymore. Conclusions : Pretreatment with statins seems to be associated with reduced clinical severity in patients with acute ischemic cerebrovascular events, particularly in patients with diabetes.

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.

Background and Purpose — Oral anticoagulation (OAC) and antiplatelet drugs are effective in the secondary prevention of ischemic cerebrovascular events. Only few data exist about the factors influencing the choice of a specific therapy for secondary prevention in patients with a recent stroke or transient ischemic attack (TIA). Methods — Within a cross-sectional study, nested in a cohort we identified 931 patients with a recent ischemic stroke or TIA who were discharged with OAC or with one of the antiplatelet medications aspirin, clopidogrel, or the combination of aspirin and extended-release dipyridamole. By means of multivariate logistic regression analysis, we determined the influence of several clinical variables on the decision between OAC and overall antiplatelet therapy as well as on the decision between different antiplatelet therapies. Results — A cardioembolic etiology of the index event and atrial fibrillation were independently associated with the use of OAC. Age was inversely associated with the use of OAC. Different estimations of contraindications to OAC were the main reason for the considerable variability among the participating centers. The most important factor promoting the use of clopidogrel was therapy with aspirin before the index event. Patients with large- or small-vessel disease received clopidogrel more often than those with an event of undetermined etiology. We found an extremely high interhospital variability for the use of the combination of aspirin with extended-release dipyridamole. Conclusions — Current recommendations are applied in clinical practice, but great variability between different centers remains. More clearly defined guidelines for indications for, as well as contraindications against, a specific therapy are necessary.

Genetic risk factors play an important role in the aetiology of vascular diseases. The insertion/deletion polymorphism (4G/5G) in the promotor region of the plasminogen activator inhibitor 1 (PAI-1) gene has been associated with an increased risk of myocardial infarction. We investigated 136 patients with minor stroke (MS) and transient ischaemic attack (TIA) and found a prevalence of 0.32 for the 4G/4G genotype in patients compared with 0.42 in 115 age-matched healthy controls. The 4G/4G genotype was significantly less frequent among 61 patients symptomatic before the age of 60 years (prevalence 0.20) than in 75 patients symptomatic after 60 years of age (prevalence 0.42; odds ratio). Our results indicate that the 4G/4G genotype is not a risk factor for MS or TIA and may even be protective in young patients.

It was the aim of this study to determine the associations of clinical and laboratory data with plasma homocyst(e)ine levels in patients with transient ischemic attack (TIA) or minor stroke (MS), with special reference to their 677C to T mutation status in the 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR) gene. Seventy-six patients with TIA or MS were investigated at least 3 months after their (last) clinical event. By means of univariate analysis, significant correlations of homocyst(e)ine levels with male gender (P0.02), age (P0.0005), creatinine levels (P0.0002), folate levels (inversely, P0.05), and alcohol use (P0.02) were found, but not with vitamin B12 levels. Multivariate regression analysis, including age, creatinine levels, and folate levels as independent variables, revealed age (P0.01) and creatinine levels (P0.02) to be significantly correlated with homocyst(e)ine levels. After adjustment for age, creatinine levels and homocyst(e)ine levels remained significantly correlated to each other (P0.005), whereas the relation between folate levels and homocyst(e)ine levels was no longer significant (P=0.10). Mutation-positive patients exhibited moderately and statistically non-significantly higher homocyst(e)ine levels than mutation-negative patients, particularly those who were homozygous positive. Homocyst(e)ine levels were closely correlated with creatinine levels (P0.0002) and with folate levels (inversely, P0.05), but only in mutation-positive and not in mutation-negative patients. Homozygous positive, heterozygous positive, and mutation-negative patients did not differ with respect to clinical and laboratory data concerning 'risk factors for stroke' or co-existing vascular disease. In conclusion, the associations of creatinine levels and, inversely, of folate levels with plasma homocyst(e)ine levels in patients with TIA or MS are dependent on the 5,10-MTHFR mutation status. Significant correlations between these variables were found only in mutation-positive but not in mutation-negative patients.

Event-related brain potentials (ERPs) were used to investigate the time course of memory processes following the presentation of faces. Following a phase in which subjects were asked to memorise faces presented on a computer screen (study phase) they had to distinguish the previously presented faces from others new to the experiment (test phase). We found that in a time period from 250 to 350 ms after onset of stimulus presentation ERPs show higher negativity for both repeated and novel faces in the test phase compared to the study phase. This situation dependent effect is most pronounced in occipito-temporal regions. We conclude that memory retrieval for faces is a sequential process. The early part of this process constitutes preparation for the retrieval of stored information, and a later part of the process comprises the discrimination between repeated and novel faces.