INTRODUCTION:Thrombosis of cerebral veins or sinuses (CVST) is a rare condition. In a monocentric retrospective cohort study the clinical characteristics, risk factors, radiological findings as well as course and prognosis of patients over the past 15 years were examined. METHODS:Between January 1998 and March 2013 all patients who were treated as inpatients for CVST at the department of neurology of the University of Heidelberg were systematically registered in a database. Along with all relevant clinical data the modified Rankin scale (MRS) was used to measure the clinical severity. A follow-up visit was performed at three time points. The odds ratios (OR) were calculated to establish predictors of good outcome (MRS 0-2), mortality at discharge and at follow-up. Significant variables after univariate analysis were tested for independency in a multivariate logistic regression model. RESULTS:A total of 143 patients were included in the study. The median age was 43 years (range 17-74 years) and 67.4 % of patients were female. The most common symptoms were headache (70.6 %), seizures (50.4 %) and paresis (37.8 %). The most prominent clinical risk factor was oral contraception (40.4 %). The two most common localizations of thrombosis were the transversal sinus with the sigmoid sinus (66.4 %) and the sagittal superior sinus (47.6 %). On admission 42.7 % of patients suffered additionally from intracerebral hemorrhage and 12.6 % from congestive infarction. Of the patients 9.5 % (10 out of 105) showed a pathologically reduced activated protein C (APC) resistance and 8.4 % (6 out of 94) a prothrombin mutation. All patients were initially treated with heparin and 88.7 % were switched to cumarin during the course of the disease. The median duration of anticoagulation was 15.75 months (range 1-121 months). On discharge 77.7 % had a good outcome and the in-hospital mortality was 4.7 %. The median time to follow-up in 108 patients was 36 months (range 3-132 months), 74.1 % of patients had a good outcome (MRS 0-2) and 18.5 % died. Independent predictors of in-hospital mortality were MRS on admission (OR 2.2, 95 % CI 1.03-4.7) and of mortality at follow-up the presence of a malignant disease (OR 50.2, 6-423) and intracerebral hemorrhage on admission (OR 10.3, 1.7-62.6). DISCUSSION:The results of this study are in line with previously published data on CVST. The most prominent clinical risk factors for CVST were female gender and oral contraception. At discharge from hospital and 3 years after CVST approximately 75 % of patients achieved a good clinical outcome. A severe clinical syndrome and the presence of an intracerebral hemorrhage on admission were independent predictors of mortality.

Die zerebrale Sinus-/Venenthrombose (SVT) ist eine seltene Erkrankung, bei der es zu einem thrombotischen Verschluss zerebraler Venen oder Sinus kommt. Wir untersuchten in einer monozentrischen retrospektiven Kohortenstudie klinische Charakteristika, Risikofaktoren, Bildgebungsbefunde und die Prognose unserer Patienten über einen Zeitraum von 15 Jahren.

Background and purposeRisk factors for IS in young adults differ between genders and evolve with age, but data on the age‐ and gender‐specific differences by stroke etiology are scare. These features were compared based on individual patient data from 15 European stroke centers.MethodsStroke etiology was reported in detail for 3331 patients aged 15–49 years with first‐ever IS according to Trial of Org in Acute Stroke Treatment (TOAST) criteria: large‐artery atherosclerosis (LAA), cardioembolism (CE), small‐vessel occlusion (SVO), other determined etiology, or undetermined etiology. CE was categorized into low‐ and high‐risk sources. Other determined group was divided into dissection and other non‐dissection causes. Comparisons were done using logistic regression, adjusting for age, gender, and center heterogeneity.ResultsEtiology remained undetermined in 39.6%. Other determined etiology was found in 21.6%, CE in 17.3%, SVO in 12.2%, and LAA in 9.3%. Other determined etiology was more common in females and younger patients, with cervical artery dissection being the single most common etiology (12.8%). CE was more common in younger patients. Within CE, the most frequent high‐risk sources were atrial fibrillation/flutter (15.1%) and cardiomyopathy (11.5%). LAA, high‐risk sources of CE, and SVO were more common in males. LAA and SVO showed an increasing frequency with age. No significant etiologic distribution differences were found amongst southern, central, or northern Europe.ConclusionsThe etiology of IS in young adults has clear gender‐specific patterns that change with age. A notable portion of these patients remains without an evident stroke mechanism according to TOAST criteria.

Background and purposeIt has been suggested that inflammation may play a role in the development of cervical artery dissection (CeAD), but evidence remains scarce.MethodsA total of 172 patients were included with acute (< 24 h) CeAD and 348 patients with acute ischaemic stroke (IS) of other (non‐CeAD) causes from the Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) study, and 223 age‐ and sex‐matched healthy control subjects. White blood cell (WBC) counts collected at admission were compared across the three groups.ResultsCompared with healthy control subjects, CeAD patients and non‐CeAD stroke patients had higher WBC counts (P < 0.001). Patients with CeAD had higher WBC counts and were more likely to have WBC > 10 000/μl than non‐CeAD stroke patients (38.4% vs. 23.0%, P < 0.001) and healthy controls (38.4% vs. 8.5%, P < 0.001). WBC counts were higher in CeAD (9.4 ± 3.3) than in IS of other causes (large artery atherosclerosis, 8.7 ± 2.3; cardioembolism, 8.2 ± 2.8; small vessel disease, 8.4 ± 2.4; undetermined cause, 8.8 ± 3.1; P = 0.022). After adjustment for age, sex, stroke severity and vascular risk factors in a multiple regression model, elevated WBC count remained associated with CeAD, as compared with non‐CeAD stroke patients [odds ratio (OR) = 2.56; 95% CI 1.60–4.11; P < 0.001) and healthy controls (OR = 6.27; 95% CI 3.39–11.61; P < 0.001).ConclusionsAcute CeAD was associated with particularly high WBC counts. Leukocytosis may reflect a pre‐existing inflammatory state, supporting the link between inflammation and CeAD.

Background and purpose: To analyze previously established gender differences in cervical artery dissection (CeAD).Methods: This case–control study is based on the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) population comprising 983 consecutive CeAD patients (mean age: 44.1 ± 9.9 years) and 658 control patients with a non‐CeAD ischemic stroke (IS) (44.5 ± 10.5 years).Results: Cervical artery dissection was more common in men (56.7% vs. 43.3%, P < 0.001) and men were older (46.4 vs. 41.0 years, P < 0.001). We assessed putative risk factors for CeAD including vascular risk factors, recent cervical trauma, pregnancies, and infections. All gender differences in the putative risk factors and outcome were similar in the CeAD and the non‐CeAD IS groups.Conclusion: Our analysis of the largest collection of CeAD patients to date confirms male predominance and differences in age at dissection between men and women. Gender differences in putative risk factors may explain the higher frequency of CeAD in men and their older age, but the putative risk factors are probably not specific for CeAD.

Background and Purpose - The vitamin K-dependent protein Z (PZ) has been shown to possess anticoagulant as well as procoagulant properties. Plasma levels of PZ show a broad interindividual variation, but it is unknown to which extent this variation is under genetic control. Recent clinical studies revealed contradictory results on the association of PZ plasma levels and the risk of ischemic stroke. Methods - We performed a case-control study including 200 patients with cerebral ischemia aged less than or equal to50 years and 199 control subjects from the same South German region. We investigated a possible association of 2 common single nucleotide mutations in the PZ gene with the risk of cerebral ischemia. Furthermore, enzyme-linked immunosorbent assay measurements were done in control subjects without vascular disease to detect a potential association of different genotypes with PZ plasma ( antigen) levels. Results - In patients, the frequency of the A allele of the intron F polymorphism G79A was significantly lower than in controls (15.7% versus 24.4%; odds ratio, 0.58; 95% CI, 0.39 to 0.86; P = 0.007; adjusted for age, sex, and conventional risk factors). The G allele of the promoter polymorphism A-13G tended to be less common in patients (4.2% versus 7.0%; adjusted odds ratio, 0.56; 95% CI, 0.28 to 1.13; P = 0.105). In 42 control subjects, the A allele of the intron F polymorphism was associated with lower PZ antigen levels ( P = 0.0032; Spearman correlation coefficient r(s) = -0.48). Conclusions - The A allele of an intron F polymorphism of the PZ gene appears to be a novel protective genetic marker for the risk of cerebral ischemia in young adults. In the context of juvenile stroke, high PZ plasma levels may represent a prothrombotic condition.

BACKGROUND:Spinocerebellar ataxia type 17 (SCA17) is caused by abnormal expansions of CAG/CAA trinucleotides within the TATA-box binding protein gene (TBP). The currently accepted critical threshold of abnormal expansions is ≥43.OBJECTIVE:To investigate the minimal CAG/CAA expansion within the TBP in SCA17.RESULTS:285 patients with autosomal-dominant ataxia were examined, and abnormal or borderline expansions of CAG/CAA within TBP in eight cases were found. Of those, four patients from three families had exactly 42 CAG/CAA trinucleotides, that is, one codon less than the currently accepted critical threshold of 43. The four patients presented with a relatively benign phenotype. All had dysdiadochokinesia and dysarthria. Mild gait ataxia was observed in three of the four patients.CONCLUSION:The reference definition of at least 43 CAG/CAA codons for pathological SCA17 alleles should be lowered to 42.

Acute stroke must be considered as an emergency with highest priority. The same is true for patients with transient ischemic attacks, given their high risk for following stroke events within the first 48 hours. Early brain imaging is essential for discrimination of either ischemic or hemorrhagic stroke. In acute ischemic stroke, rapid establishment of reperfusion is the major therapeutic goal. This is achieved by intravenous thrombolysis, in selected cases by an intraarterial approach with pharmaceutical and/or mechanical recanalization. The effect of successful reperfusion is highly dependent on time: the earlier, the better the odds for substantial clinical improvement. The recent extension of the time window for systemic thrombolysis to 4.5 hours must not result in any delays of diagnosis and treatment initiation! Stroke units with facilities for early etiological workup with according secondary prevention measures, for prevention and treatment of complications, and for early rehabilitation have been shown to yield the best outcome for all stroke victims.

Die 2007 aus der European Stroke Initiative und dem European Stroke Council hervorgegangene Europäische Stroke Organisation (ESO) hatte zuletzt 2008 umfassende deutschsprachige Leitlinien zum Management von Patienten mit akutem Hirninfarkt und TIA veröffentlicht. Im Jahr 2009 wurden diese Leitlinien nach den Ergebnissen der ECASS-III-Studie aktualisiert, indem die Thrombolysetherapie mit Alteplase nun bis zu 4,5 h nach Symptombeginn empfohlen wird (Klasse I, Grad-A-Empfehlung). Die vorliegende Kurzfassung der aktuellen englischsprachigen Leitlinien wendet sich an die ärztlichen und nichtärztlichen Schlaganfall-Primärversorger. Für eine detaillierte Darstellung, insbesondere auch der Empfehlungen zur Primär- und Sekundärprophylaxe sowie zur Komplikationsvermeidung, wird auf die ausführliche Version der Leitlinien, online verfügbar unter http://www.eso-stroke.org, verwiesen.

Genome‐wide association studies consistently found an association between loci on the genetic region 9p21 and coronary artery disease [1Schunkert H. Götz A. Braund P. McGinnis R. Tregouet D.A. Mangino M. Linsel‐Nitschke P. Cambien F. Hengstenberg C. Stark K. Blankenberg S. Tiret L. Ducimetiere P. Keniry A. Ghori M.J. Schreiber S. El Mokhtari N.E. Hall A.S. Dixon R.J. Goodall A.H. et al.Repeated replication and a prospective meta‐analysis of the association between chromosome 9p21.3 and coronary artery disease.Circulation. 2008; 117: 1675-84Crossref PubMed Scopus (0) Google Scholar]. The two single nucleotide polymorphisms (SNPs) rs10757274 and rs10757278, located in the same linkage disequilibrium (LD) block on Chromosome 9, were among the strongest correlates for the association. Recently, four studies investigated the association of these SNPs with ischemic stroke [2Zee R.Y. Ridker P.M. Two common gene variants on chromosome 9 and risk of atherothrombosis.Stroke. 2007; 38: e111Crossref PubMed Scopus (0) Google Scholar, 3Helgadottir A. Thorleifsson G. Magnusson K.P. Grétarsdottir S. Steinthorsdottir V. Manolescu A. Jones G.T. Rinkel G.J. Blankensteijn J.D. Ronkainen A. Jääskeläinen J.E. Kyo Y. Lenk G.M. Sakalihasan N. Kostulas K. Gottsäter A. Flex A. Stefansson H. Hansen T. Andersen G. et al.The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm.Nat Genet. 2008; 40: 217-24Crossref PubMed Scopus (599) Google Scholar, 4Matarin M. Brown W.M. Singleton A. Hardy J.A. Meschia J.F. ISGS investigators. Whole genome analyses suggest ischemic stroke and heart disease share an association with polymorphisms on chromosome 9p21.Stroke. 2008; 39: 1586-9Crossref PubMed Scopus (0) Google Scholar, 5Lemmens R. Abboud S. Robberecht W. Vanhees L. Pandolfo M. Thijs V. Goris A. Is the recently identified snp on chromosome 9p a cardiospecific genetic risk factor? results from three case‐control studies.Cerebrovasc Dis. 2008; 25: 1-192PubMed Google Scholar]. Arterial stroke at a young age is a heterogeneous condition, whose etiology remains largely unknown. Thus, efforts to identify novel risk factors for premature cerebral ischemia have relevant public health implications. We investigate the association between ischemic stroke at a young age and rs10757274 and rs10757278 SNPs in two case‐control studies and perform a meta‐analysis on the association between SNPs on genetic region 9p21 and ischemic stroke. Patients with first‐ever ischemic stroke (n = 252) occurring before the age of 45 years, consecutively admitted to the Department of Neurology, University of Brescia, and control subjects (n = 189) recruited from the general population, with no known history of vascular disease, frequency‐matched to the cases by sex and age, were included in the Italian study [6Iacoviello L. Di Castelnuovo A. Gattone M. Pezzini A. Assanelli D. Lorenzet R. Del Zotto E. Colombo M. Napoleone E. Amore C. D’Orazio A. Padovani A. De Gaetano G. Giannuzzi P. Donati M.B. IGIGI Investigators. Polymorphisms of the interleukin‐1beta gene affect the risk of myocardial infarction and ischemic stroke at young age and the response of mononuclear cells to stimulation in vitro.Arterioscler Thromb Vasc Biol. 2005; 25: 222-7Crossref PubMed Scopus (150) Google Scholar]. Consecutive patients (n = 151) aged less than 50 years, who were admitted to the Department of Neurology, University of Heidelberg, for ischemic stroke, and control subjects (n = 198) without a history of vascular disease randomly selected from the population registries of the same region in southwest Germany were included in the German study [7Lichy C. Kropp S. Dong‐Si T. Genius J. Dolan T. Hampe T. Stoll F. Reuner K. Grond‐Ginsbach C. Grau A. A common polymorphism of the protein Z gene is associated with protein Z plasma levels and with risk of cerebral ischemia in the young.Stroke. 2004; 35: 40-5Crossref PubMed Scopus (0) Google Scholar]. The rs10757274 and rs10757278 SNP were genotyped by TaqMan SNP Genotyping Assays (Assays‐on‐Demand; Applied Biosystems, Foster City, CA, USA), containing probes for both alleles labelled with either FAM or VIC dyes. A search of the MEDLINE, PubMed, and EMBASE databases was performed to find papers that investigated the association of SNPs in the region 9p21 with ischemic stroke, written in English, and published until September 2008. Multivariable logistic‐regression analysis was adjusted for age, sex, smoking status, hyperlipidemia and hypertension. Haplotypes were inferred and analyzed using the package Haplo.Stats (http://mayoresearch.mayo.edu/mayo/research/schaid:lab/software.cfm; accessed 10 December). Data from different studies were combined by using the fixed model general variance‐based method. Chi‐square with degrees of freedom one less than the number of studies was used to assess heterogeneity. All computations were performed with the SAS statistical package (Version 9.1.3 for Windows; SAS Institute). Genotypes distributions were in Hardy‐Weinberg equilibrium, both in cases and in controls, and the two SNPs were in strong LD. Italian patients with stroke smoked more and had a higher incidence of hypertension, diabetes and hypercholesterolemia than controls. For the rs10757274 SNP, the AA/AG/GG genotypes distribution was 50/96/43 in controls and 79/132/41 in cases (P = 0.093 for alleles difference, and P = 0.19 for genotypes difference). For the rs10757278 SNP, the AA/AG/GG genotypes distribution was 50/91/48 in controls and 81/117/54 in cases (P = 0.16 for alleles difference, and P = 0.37 for genotypes difference). German patients with stroke had a higher incidence of hypertension and diabetes than controls. For the rs10757274 SNP, the AA/AG/GG genotypes distribution was 49/99/50 in controls and 35/72/44 in cases (P = 0.47 for alleles difference, and P = 0.72 for genotypes difference). For the rs10757278 SNP, the AA/AG/GG genotypes distribution was 45/103/50 in controls and 37/70/44 in cases (P = 0.78 for alleles difference, and P = 0.56 for genotypes difference). Any statistically significant association of SNPs or haplotypes with stroke in all multivariable models of inheritance analyses was observed, both in Italian and in German studies (Fig. 1). Three articles and one abstract were found on the association between chromosome 9p21 polymorphisms and ischemic stroke, including a total of six populations. In the study by Zee and Ridker [2Zee R.Y. Ridker P.M. Two common gene variants on chromosome 9 and risk of atherothrombosis.Stroke. 2007; 38: e111Crossref PubMed Scopus (0) Google Scholar] the authors measured the SNP rs10757274, whereas Helgadottir et al. [3Helgadottir A. Thorleifsson G. Magnusson K.P. Grétarsdottir S. Steinthorsdottir V. Manolescu A. Jones G.T. Rinkel G.J. Blankensteijn J.D. Ronkainen A. Jääskeläinen J.E. Kyo Y. Lenk G.M. Sakalihasan N. Kostulas K. Gottsäter A. Flex A. Stefansson H. Hansen T. Andersen G. et al.The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm.Nat Genet. 2008; 40: 217-24Crossref PubMed Scopus (599) Google Scholar] and Lemmens et al. [5Lemmens R. Abboud S. Robberecht W. Vanhees L. Pandolfo M. Thijs V. Goris A. Is the recently identified snp on chromosome 9p a cardiospecific genetic risk factor? results from three case‐control studies.Cerebrovasc Dis. 2008; 25: 1-192PubMed Google Scholar] measured the SNP rs10757278. Matarin et al. [4Matarin M. Brown W.M. Singleton A. Hardy J.A. Meschia J.F. ISGS investigators. Whole genome analyses suggest ischemic stroke and heart disease share an association with polymorphisms on chromosome 9p21.Stroke. 2008; 39: 1586-9Crossref PubMed Scopus (0) Google Scholar] evaluated five SNPs, all existing within the same LD block. In particular, the rs2383207 measured by Matarin et al. is in absolute LD with rs10757278, according to the HapMap database (http://www.hapmap.org). The SNP rs10757274 exists within the same LD block as rs2383207 and rs10757278. Moreover, Zee and Ridker reported genotypic specific odds ratios instead of odds ratio for additive model. Consequently, we decided to conduct two separate meta‐analyses: the first pooled the findings from Zee and Ridker with that from our Italian and German populations, using genotype specific odds ratios for the SNP rs10757274; and the second pooled the findings from Helgadottir et al. (after exclusion of patients with concomitant coronary artery disease), Matarin et al. and Lemmens et al. with that from our Italian and German populations, using odds ratios for the additive model for the SNP rs10757278 (rs2383207 for the study of Matarin et al.). Results are depicted in the figure. None of the individual studies showed significant associations with stroke. The overall odds ratios were 0.98 (95% CI, 0.73 to 1.31) and 1.04 (95% CI, 0.74 to 1.47) in the firs meta‐analysis, and 1.02 (95% CI, 0.94 to 1.11) in the second, without evidence of heterogeneity (Fig. 1). Our findings demonstrate absence of association between ischemic stroke at a young age and two polymorphisms in genetic region 9p21, in two populations of white Europeans from Italy and Germany. Our data are in agreement with those published by Zee and Ridker [2Zee R.Y. Ridker P.M. Two common gene variants on chromosome 9 and risk of atherothrombosis.Stroke. 2007; 38: e111Crossref PubMed Scopus (0) Google Scholar], which found no association between rs10757274 SNP and the risk of ischemic stroke in 254 US white case‐control pairs from the Physicians’ Health Study. Similar results were shown by Lemmens et al. [5Lemmens R. Abboud S. Robberecht W. Vanhees L. Pandolfo M. Thijs V. Goris A. Is the recently identified snp on chromosome 9p a cardiospecific genetic risk factor? results from three case‐control studies.Cerebrovasc Dis. 2008; 25: 1-192PubMed Google Scholar] and Helgadottir et al. [3Helgadottir A. Thorleifsson G. Magnusson K.P. Grétarsdottir S. Steinthorsdottir V. Manolescu A. Jones G.T. Rinkel G.J. Blankensteijn J.D. Ronkainen A. Jääskeläinen J.E. Kyo Y. Lenk G.M. Sakalihasan N. Kostulas K. Gottsäter A. Flex A. Stefansson H. Hansen T. Andersen G. et al.The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm.Nat Genet. 2008; 40: 217-24Crossref PubMed Scopus (599) Google Scholar], who studied the SNP rs10757278. In the large study by Helgadottir et al. [3Helgadottir A. Thorleifsson G. Magnusson K.P. Grétarsdottir S. Steinthorsdottir V. Manolescu A. Jones G.T. Rinkel G.J. Blankensteijn J.D. Ronkainen A. Jääskeläinen J.E. Kyo Y. Lenk G.M. Sakalihasan N. Kostulas K. Gottsäter A. Flex A. Stefansson H. Hansen T. Andersen G. et al.The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm.Nat Genet. 2008; 40: 217-24Crossref PubMed Scopus (599) Google Scholar] this variant showed a consistent strong association with coronary heart disease, while it had a marginal effect on LAA/cardiogenic stroke. However, after excluding patients with known CAD from the analysis, the effect of the variant was no more significant. In the study by Matarin et al. [4Matarin M. Brown W.M. Singleton A. Hardy J.A. Meschia J.F. ISGS investigators. Whole genome analyses suggest ischemic stroke and heart disease share an association with polymorphisms on chromosome 9p21.Stroke. 2008; 39: 1586-9Crossref PubMed Scopus (0) Google Scholar] a significant association was seen between ischemic stroke and SNPs located within the same LD block as rs10757274 and rs10757278, but that association was marked at the haplotype level, whereas single SNPs were not statistically associated in multivariable analyses. The findings from Matarin et al. [4Matarin M. Brown W.M. Singleton A. Hardy J.A. Meschia J.F. ISGS investigators. Whole genome analyses suggest ischemic stroke and heart disease share an association with polymorphisms on chromosome 9p21.Stroke. 2008; 39: 1586-9Crossref PubMed Scopus (0) Google Scholar] are of interest, because we can argue that genetic variants play their role within the context of the haplotype. We analyzed haplotypes from the two SNPs rs10757274 and rs10757278, but failed to find an association with stroke. Additional studies aimed at confirming the association between haplotypes in 9p21 and stroke are needed. Two meta‐analyses confirmed a lack of association of these polymorphisms with ischemic stroke. A potentially major concern of our meta‐analysis is the appropriateness of combining results of studies with very different age ranges for the cases. It seems possible that the etiology of early‐onset stroke may differ from the later‐onset cases that were the focus of the prior literature. Although additional studies with larger sample size of more homogenous stroke patients and able to investigate haplotype effects are needed to draw clear conclusions, our data support the idea that the variants rs10757274, rs10757278 and rs2383207, located in a LD block in the region 9p21, and strongly associated with a 24% to 31% higher risk of cardiovascular disease [1Schunkert H. Götz A. Braund P. McGinnis R. Tregouet D.A. Mangino M. Linsel‐Nitschke P. Cambien F. Hengstenberg C. Stark K. Blankenberg S. Tiret L. Ducimetiere P. Keniry A. Ghori M.J. Schreiber S. El Mokhtari N.E. Hall A.S. Dixon R.J. Goodall A.H. et al.Repeated replication and a prospective meta‐analysis of the association between chromosome 9p21.3 and coronary artery disease.Circulation. 2008; 117: 1675-84Crossref PubMed Scopus (0) Google Scholar], did not show a similar involvement in ischemic stroke. LI and her associates were supported by MIUR (Ministero dell’Università e Ricerca, Italia), Programma Triennale di Ricerca, grant D. 1588. The authors state that they have no conflict of interest.

P>Objective: The exposure of tissue factor (TF) to blood flow is the initial step in the coagulation process and plays an important role in thrombogenesis. We investigated the role of genetic polymorphisms and haplotypes of the TF gene in the risk of ischemic vascular disease. Methods: Four hundred and twenty-two Italian patients with juvenile myocardial infarction (MI) and 434 controls, 808 US cases with MI and 1005 controls, 267 Italian cases with juvenile ischemic stroke and 209 controls and 148 German cases with juvenile ischemic stroke and 191 controls were studied. rs1361600, rs3917629 (rs3354 in the US population), rs1324214 and rs3917639 Tag single nucleotide polymorphisms were genotyped. Additionally, a meta-analysis of all previous studies on TF loci and the risk of ischemic coronary disease (ICD) was performed. Results: After multivariable analysis none of the SNPs, major SNP haplotypes or haplotype-pairs showed any consistent association with MI. Pooled meta-analysis of six studies also suggested that TF polymorphisms are not associated with CHD. A significant, independent association between SNP rs1324214 (C/T) and juvenile stroke was found in Italian and German populations (OR for TT homozygotes = 0.47, 95% CI 0.24-0.92, in combined analysis). Pooled analysis also showed a significant association for haplotype H3 (OR = 0.76, 95% CI 0.57-1.00) and haplotype-pair H3-H3 (OR = 0.43, 95% CI 0.20-0.92). Conclusions: TF genetic variations were associated with the risk of ischemic stroke at young age, but did not affect ischemic coronary disease.

Telemedicine is increasingly being utilised for the remote evaluation of stroke patients, particularly in neurologically underserved areas. It is usually based on video examination and teleradiological evaluations of brain scans. Scientific analyses have demonstrated the reliability of neurological scores assessed via videoconference. Teleradiology using electronically transmitted original imaging data is potentially equivalent to onsite assessment. Intravenous thrombolysis can be indicated with similar results as in experienced stroke centres if both technological and professional quality standards are applied. However, improved clinical outcomes of stroke patients have only been shown when telemedicine was combined with the Stroke Unit concept based on specialised stroke wards and organised stroke care. More scientific evaluation is needed in the fields of cost effectiveness, quality management and implementation of further technological innovations. There are still insufficient data about the use of telemedicine in prevention, rehabilitation and post-stroke care and a comprehensive scientific evaluation is still needed.

Telemedizinische Anwendungen mit klinischer Untersuchung des Patienten über Videokonferenz und Fernbefundung der zerebralen Schnittbildgebung haben verbreitete Nutzung in der akuten Schlaganfallversorgung insbesondere in Regionen mit unzureichenden neurologischen Behandlungseinrichtungen gefunden. Wissenschaftliche Untersuchungen haben die Zuverlässigkeit der neurologischen Fernuntersuchung bestätigt und die Indikation für die systemische Lysetherapie kann über Telekonsile mit entsprechenden technischen Qualitätsstandards sicher gestellt werden. Eine Verbesserung klinischer Behandlungsergebnisse konnte bisher aber nur gezeigt werden, wenn die Telemedizin in das Konzept der Stroke Unit mit spezialisierten Schlaganfalleinheiten und entsprechenden Qualitätsstandards eingebettet wurde. Außerhalb eines derartigen integrierten Konzeptes ist ein klinisches Benefit nicht nachgewiesen. Forschungsbedarf besteht im Bereich der Kosteneffizienz, des Qualitätsmanagements und der Implementierung weiterer technologischer Innovationen. Der Einsatz der Telemedizin in der Prävention, prähospitalen Schlaganfallversorgung, Rehabilitation und ambulanten Nachsorge ist nicht ausreichend untersucht und bedarf einer konsequenten wissenschaftlichen Evaluation.

In Deutschland hat sich in den letzten Jahren er− freulicherweise eine veränderte Wahrnehmung des Schlaganfalls als zum guten Teil vermeidbare und vor allem effektiv behandelbare Erkrankung durchgesetzt. Der Schlaganfall ist bereits heute die häufigste Ursache für eine erworbene Behin− derung und gehört zu den führenden Todesursa− chen. Bedingt durch den demografischen Wandel wird eine weitere Zunahme der Schlaganfallinzi− denz für die nächsten 2 Jahrzehnte erwartet: im 5−Jahres−Zeitraum von 2021±2025 voraussicht− lich um ein Drittel höher als von 2005±2010 [1]. Dies geht einher mit einer dramatischen Belas− tung der Sozialsysteme [1]. Die 4 evidenzbasier− ten Therapieformen des akuten Schlaganfalls umfassen die frühe Aspiringabe bei Hirninfark− Zusammenfassung !

Background Cervical artery dissection (CAD) is a frequent cause of ischemic stroke, and occasionally death, in young adults. Several lines of evidence suggest a genetic predisposition to CAD. However, previous genetic studies have been inconclusive mainly due to insufficient numbers of patients. Our hypothesis is that CAD is a multifactorial disease caused by yet largely unidentified genetic variants and environmental factors, which may interact. Our aim is to identify genetic variants associated with an increased risk of CAD and possibly gene-environment interactions. Methods We organized a multinational European network, Cervical Artery Dissection and Ischemic Stroke Patients (CADISP), which aims at increasing our knowledge of the pathophysiological mechanisms of this disease in a large group of patients. Within this network, we are aiming to perform a de novo genetic association analysis using both a genome-wide and a candidate gene approach. For this purpose, DNA from approximately 1100 patients with CAD, and 2000 healthy controls is being collected. In addition, detailed clinical, laboratory, diagnostic, therapeutic, and outcome data are being collected from all participants applying predefined criteria and definitions in a standardized way. We are expecting to reach the above numbers of subjects by early 2009. Conclusions We present the strategy of a collaborative project searching for the genetic risk factors of CAD. The CADISP network will provide detailed and novel data on environmental risk factors and genetic susceptibility to CAD.

Background: The TT genotype of a functional factor XII (FXII) C46T gene polymorphism was shown to be a risk factor for peripheral venous thrombosis. We tested whether this genetic variant also increases the risk for cerebral venous thrombosis (CVT). Methods: We performed a case-control study including 78 consecutive patients with proven CVT and 201 healthy population controls from South Germany. The FXII C46T genotype was assessed using a PCR technique. Results: The TT genotype of the FXII C46T polymorphism was more common in patients (16.7%) than in controls (5.5%). A strong association of the TT genotype with CVT was found, which was independent of covariables (adjusted odds ratio 4.57; 95% CI 1.55 to 13.41; p = 0.006). Conclusion: The TT genotype of the functional factor XII C46T gene polymorphism may be a new independent risk factor for cerebral venous thrombosis (CVT). Our finding warrants confirmation in an independent study before this genetic variant should be added to the panel of established risk factors for CVT.

Eines der entscheidenden Hindernisse für eine flächendeckende Schlaganfallversorgung nach dem „state of the art“, insbesondere in ländlichen Regionen, ist der Mangel an rasch verfügbarer neurologischer Expertise. Telemedizinische Anwendungen mit klinisch-neurologischer Untersuchung via Videokonferenz zwischen der Aufnahmeklinik und einem spezialisierten Schlaganfallzentrum sowie teleradiologischer Bewertung der zerebralen Bildgebung können diesen Versorgungsengpass überbrücken. Tatsächlich lassen sich Schlaganfallsyndrome gut durch eine Videountersuchung erfassen. Die Indikation für die systemische Lysetherapie kann telemedizinisch ohne zeitliche Verzögerung gestellt werden. Die Versorgung auf einer Stroke Unit als insgesamt wirksamste Behandlungsstrategie kann dadurch aber nicht ersetzt werden. Wird allerdings die telemedizinische Vernetzung mit dem Stroke-Unit-Konzept und einem konsequenten Qualitätsmanagement kombiniert, können auch kleinere Krankenhäuser eine Schlaganfallversorgung auf hohem Niveau anbieten. Durch eine telemedizinisch unterstützte Optimierung von Notfalltransporten und die rasch verfügbare „second opinion“ erfahrener Schlaganfallzentren entstehen zusätzliche Perspektiven.