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Biomedical subjects

Christoph Lichy

Publications and source records attributed to Christoph Lichy.

16 recordsLinked to original sources
PubMed2006

Hemorrhagic complications after off-label thrombolysis for ischemic stroke.

BACKGROUND AND PURPOSE: Only 2% to 4% of patients with acute ischemic stroke receive thrombolytic therapy resulting from the current strict inclusion criteria among other issues. Safety of intravenous and intraarterial thrombolysis in off-label situations is controversially discussed. We sought to review the reports on such patients regarding intra- and extracranial hemorrhage. SUMMARY OF REVIEW: A MEDLINE search for off-label uses of thrombolysis revealed reports on 273 patients treated with intraarterial or intravenous thrombolysis for ischemic stroke. Symptomatic intracranial hemorrhage occurred in 19 of 273 patients (6.95%) and extracranial hemorrhage in 17 of 273 (6.22%). CONCLUSIONS: These data suggest that the overall bleeding risk in off-label thrombolysis may not be as high as presumed. However, the small number of patients in each group and the likely underreporting of worse outcomes preclude drawing any conclusion as to specific treatment recommendations. Selected patients might benefit, however, from thrombolysis in situations not currently considered in the inclusion criteria. To obtain a meaningful database, a registry for off-label thrombolysis should be created.

Brain Ischemia↗
PubMed2006

The effect of infections and vaccinations on stroke risk.

There is increasing evidence that, in addition to conventional risk factors, acute and chronic infectious diseases increase the risk of stroke. Acute infection, mainly respiratory, and both bacterial and viral infection, represent temporarily active trigger factors for cerebral ischemia. Chronic infectious diseases that may increase the risk of stroke include periodontitis, chronic bronchitis and infections with microbial antigens, such as Helicobacter pylori and Chlamydia pneumoniae. From observational studies, there is evidence that vaccination against influenza is associated with a reduced risk of stroke, myocardial infarction and all-cause mortality. This report provides an overview on the influence of infection on stroke risk and potential anti-infective strategies that may play a future role in stroke prevention.

Atherosclerosis↗
PubMed2006

Investigating the association between influenza vaccination and reduced stroke risk.

Acute infections, mainly of the respiratory tract, have consistently been demonstrated to considerably increase the risk of stroke. At present, prospective interventional trials are lacking and there is no proof of the effectiveness of any therapeutic anti-infective strategy in stroke prevention. However, some new evidence from observational studies lends support to the idea that influenza vaccination may contribute importantly to fighting stroke. Although final proof of efficacy is still missing, patients with previous cerebral ischemia and subjects of any age at high risk of stroke should be encouraged to receive annual influenza vaccination.

Humans↗
PubMed2005

Risk of cerebral venous thrombosis and novel gene polymorphisms of the coagulation and fibrinolytic systems.

BACKGROUND AND PURPOSE: Genetic thrombophilic conditions such as those associated with Factor V Leiden (FVL) and the prothrombin mutant (PT G20210A) have been identified as risk factors for cerebral venous thrombosis (CVT). Recently, a single nucleotide polymorphism (SNP) of the thrombin activatable fibrinolysis inhibitor (TAFI G-438A) has been shown to be associated with lower TAFI levels and to decrease the risk for peripheral venous thrombosis. Furthermore, a protective role in juvenile stroke was shown for a SNP of the vitamin K dependent protein Z (PZ Intron F G79A) which is linked with low PZ levels. PATIENTS AND METHODS: In 77 consecutive patients with CVT and in 203 randomly selected population controls from the same region of Southern Germany, we investigated the following functional SNPs using PCR and restriction fragment analysis techniques: TAFI G-438A, PZ Intron F G79A, FVL and PT G20210A. RESULTS: The prevalence of FVL tended to be higher (OR 2.08, 95 % CI 0.91-4.75, p = 0.06) and that of PT G20210A (OR 4.57, 95 % CI 1.45-14.44, p = 0.007) was significantly higher in patients with CVT than in controls. The A-allele frequency of the TAFI G-438A polymorphism did not significantly differ between patients (21.3 %) and controls (26.9%; OR 0.71, 95 % CI 0.45-1.12; p = 0.17). For the PZ G79A SNP, the frequency of the A-allele was 19.5% in CVT and 24.6% in controls (OR 0.77, 95 % CI 0.49-1.21; p = 0.31). CONCLUSIONS: In this large series of CVT patients, a positive association with established thrombophilic risk factors FVL and especially the PT G20210A mutation was confirmed. In contrast, our study found no significant association of CVT with SNPs of the TAFI and the PZ genes. Other than testing for FVL and the PT G20210A mutation, exploration of these potential thrombophilic variants seems to be of limited value in the investigation of CVT.

Adolescent↗
PubMed2005

Influenza vaccination is associated with a reduced risk of stroke.

BACKGROUND AND PURPOSE: Vascular death rates and hospitalizations for stroke are increased during influenza epidemics. Influenza vaccination may prevent stroke. We investigated whether influenza vaccination is associated independently with reduced odds of stroke and whether effects are confined to stroke subgroups and winter seasons and shared by other vaccinations. METHODS: During 18 months, we performed standardized interviews assessing vaccination status, risk factors, health-related behavior, and socioeconomic factors in 370 consecutive patients with ischemic or hemorrhagic stroke or transient ischemic attack (TIA) and 370 age- and sex-matched control subjects selected randomly from the population. RESULTS: Influenza vaccination during the last vaccination campaign was less common in patients (19.2%) than control subjects (31.4%; P<0.0001). After adjustment for vascular risk factors, education, health-related behavior and other factors, influenza vaccination (odds ratio [OR], 0.46; 95% CI, 0.28 to 0.77) but not other combined recent vaccinations (OR, 0.80; 95% CI, 0.42 to 1.43) were associated with reduced odds of stroke/TIA. Significant effects were found in men, older subjects (>65 years), subjects with previous vascular diseases, and regarding ischemic stroke; nonsignificant trends existed in women, younger subjects, and regarding hemorrhagic stroke. In etiologic subgroups of cerebral ischemia, similar effects were found. No protective effects were found during summer months; however, results also varied considerably between both winter seasons examined. CONCLUSIONS: These results support the hypothesis that influenza vaccination may be associated with reduced stroke risk. However, residual confounding cannot be excluded, and interventional studies are required to evaluate the role of influenza vaccination in stroke prevention.

Age Factors↗
PubMed2005

Postacute C-reactive protein levels are elevated in cervical artery dissection.

BACKGROUND AND PURPOSE: C-reactive protein (CRP) is associated with atherogenesis and stroke in mostly elderly subjects. We tested whether elevated CRP may also be linked to spontaneous cervical artery dissection (CAD) and cryptogenic stroke. METHODS: We investigated high-sensitivity CRP levels in 62 patients <60 years of age experiencing cerebral ischemia resulting from large artery atherosclerosis (LAA; n=21), CAD (n=21), or cryptogenic etiology (n=20) >9 months ago, and in 54 sex- and age-matched population controls. Receiver operating characteristic curve was used to identify the best CRP cutoff level for dichotomization. RESULTS: CRP was elevated above control levels (0.54 [0.33 to 0.84] median, interquartile range mg/L) in patients with LAA (2.59 [0.56 to 3.99] mg/L; P<0.001) and with CAD (2.37 [0.57 to 4.78] mg/L; P=0.0013) but not in patients with cryptogenic etiology (0.74 [0.14 to 7.86] mg/L). CRP levels above the cutoff level of 0.71 mg/L were independently associated with former CAD (P=0.005) but not with former LAA after adjustment for age, gender, and conventional risk factors. CONCLUSIONS: Our results strongly suggest that CRP is associated with CAD, independent from conventional risk factors, and that inflammatory mechanisms may play a role in its pathogenesis. This finding should be confirmed by larger studies.

Adult↗
PubMed2004

Association between cerebral ischemia and cytotoxin-associated gene-A-bearing strains of Helicobacter pylori.

BACKGROUND AND PURPOSE: Studies on Helicobacter pylori infection and risk of ischemic stroke yielded variable results. Infection with more virulent H. pylori strains, such as cytotoxin-associated gene-A (CagA)-bearing strains, may be of particular relevance for ischemic diseases. We investigated whether H. pylori and CagA seropositivity are independent risk factors for cerebral ischemia or its etiologic subtypes. METHODS: We determined IgG antibodies against H. pylori and CagA protein (enzyme immunoassays) in 190 patients with acute cerebral ischemia and in 229 age- and sex-matched control subjects selected randomly from the general population. RESULTS: CagA seropositivity was more common in patients (114/190; 60.0%) than in control subjects (99/229; 43.2%; odds ratio, 1.97; 95% CI, 1.33 to 2.91; P<0.001). This result remained significant after adjustment for age, sex, vascular risk factors and diseases, and childhood and adult social status (odds ratio, 1.84; 95% CI, 1.13 to 3.00; P=0.015). Subgroup analyses yielded similar results in all etiologic stroke subtypes. In contrast, H. pylori seropositivity in general was not associated with increased risk of stroke or its etiologic subtypes. CONCLUSIONS: Our results support the hypothesis of an association between infection with CagA-positive H. pylori strains and acute cerebral ischemia.

Adult↗
PubMed2004

Leukocyte count as an independent predictor of recurrent ischemic events.

BACKGROUND AND PURPOSE: Inflammatory markers predict first-time ischemic events. We investigated whether leukocyte and differential counts predict recurrent events and ischemic events in high-risk populations, and whether such events are preceded by acutely exacerbated inflammation. METHODS: We studied 18 558 patients with ischemic stroke, myocardial infarction, or peripheral arterial disease who participated in the trial of Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE), a study that compared the occurrence of ischemic stroke, myocardial infarction, or vascular death under randomized treatment with aspirin or clopidogrel. Leukocyte counts were frequently assessed during followup. RESULTS: Compared with the quartile with lowest leukocyte counts at baseline (<5.9x10(9)/L), patients in the top quartile (>8.2x10(9)/L) had higher risks for ischemic stroke (relative risk 1.30; P=0.007), myocardial infarction (relative risk 1.56, P<0.001), and vascular death (relative risk 1.51; P<0.001) after adjustment for other risk factors. Neutrophil counts contributed most to increased risk. Assessments of regression dilution effects based on replicate measurements show that these risk associations may underestimate the real associations by 30 to 50%. Treatment with aspirin or clopidogrel did not influence predictive effects by leukocytes. In the week before a recurrent event, but not at earlier time points, the leukocyte count was significantly increased over baseline levels (n=211; mean difference +0.46x10(9)/L; P=0.005). CONCLUSIONS: Leukocyte counts and mainly neutrophil counts are independently associated with ischemic events in these high-risk populations. An increase of leukocyte counts over baseline levels heralds a period of increased risk lasting about one week.

Aspirin↗
PubMed2004

Periodontal disease as a risk factor for ischemic stroke.

BACKGROUND AND PURPOSE: Chronic infectious diseases may increase the risk of stroke. We investigated whether periodontal disease, including periodontitis and gingivitis, is a risk factor for cerebral ischemia. METHODS: We performed a case-control study with 303 patients examined within 7 days after acute ischemic stroke or transient ischemic attack, 300 population controls, and 168 hospital controls with nonvascular and noninflammatory neurological diseases. All subjects received a complete clinical and radiographic dental examination. The individual mean clinical attachment loss measured at 4 sites per tooth served as the main indicator for periodontitis. RESULTS: Patients had higher clinical attachment loss than population (P<0.001) and hospital (P=0.010) controls. After adjustment for age, sex, number of teeth, vascular risk factors and diseases, childhood and adult socioeconomic conditions, and lifestyle factors, the risk of cerebral ischemia increased with more severe periodontitis. Subjects with severe periodontitis (mean clinical attachment loss >6 mm) had a 4.3-times-higher (95% confidence interval, 1.85 to 10.2) risk of cerebral ischemia than subjects with mild or without periodontitis (<or=3 mm). Severe periodontitis was a risk factor in men but not women and in younger (<60 years) but not older subjects. Periodontitis increased the risk of cerebral ischemia caused by large-artery atherosclerosis, cardioembolism, and cryptogenic etiology. Gingivitis and severe radiologic bone loss were also independently associated with the risk of cerebral ischemia, whereas caries was not. CONCLUSIONS: Our study indicates that periodontal disease, a treatable condition, is an independent risk factor for cerebral ischemia in men and younger subjects.

Acute Disease↗
PubMed2004

Lack of association between polymorphisms of the toll-like receptor 4 gene and cerebral ischemia.

Toll-like receptor-4 (TLR4), an important mediator of the innate immune response, is expressed in atherosclerotic lesions. The common single nucleotide exchange (Asp299Gly) of the TLR4 gene has been previously reported to impair TLR4 function and to be associated with a decreased risk of carotid atherosclerosis. Therefore, we aimed to detect the potential impact of TLR4 genotypes on the risk of cerebral ischemia. We studied the prevalence of two common polymorphisms of the TLR4 gene (Asp299Gly and Thr399Ile) in 3 independent study populations: (1.) in a cross-sectional study including 769 patients either with type 1 or type 2 diabetes mellitus, of whom 56 (7.2%) had a history of cerebral ischemia (study 1), (2.) a case-control study (study 2) including 128 consecutive patients with cerebral ischemia, mean age 60 +/- 10.9 years and 139 control subjects, and (3.) a case-control study (study 3) including 171 young adults aged < 50 years with cerebral ischemia and 204 control individuals. In all subjects, Asp299Gly and Thr399Ile were detected by restriction length analysis. The prevalence of the TLR4 genotypes was essentially the same between patients with cerebral ischemia and control subjects in all 3 study populations. Furthermore, there was also no association with the subgroup of atherosclerotic stroke in both case-control studies populations. Although TLR4 polymorphisms are associated with a decreased risk of carotid atherosclerotic lesions, our findings indicate that they do not influence the prevalence of cerebral ischemia. This implies that the Asp299Gly TLR4-allele might have a protective role in carotid atherosclerosis, but not in cerebral ischemia.

Adult↗
PubMed2004

The association of gingivitis and periodontitis with ischemic stroke.

OBJECTIVES: The aim of this study was to assess the associations of different periodontal parameters with cerebral ischemia. METHODS: In a case-control study, 303 consecutive patients with ischemic stroke or transient ischemic attack, and 300 representative population controls received a complete clinical and radiographic dental examination. Patients were examined on average 3 days after ischemia. The individual mean clinical attachment loss measured at four sites per tooth was used as indicator variable for periodontitis. RESULTS: Patients had higher clinical attachment loss than population (p<0.001). After adjustment for age, gender, number of teeth, vascular risk factors and diseases, childhood and adult socioeconomic conditions and lifestyle factors, a mean clinical attachment loss >6 mm had a 7.4 times (95% confidence interval 1.55-15.3) a gingival index >1.2 a 18.3 times (5.84-57.26) and a radiographic bone loss a 3.6 times (1.58-8.28) higher risk of cerebral ischemia than subjects without periodontitis or gingivitis, respectively. CONCLUSION: Periodontitis is an independent risk factor for cerebral ischemia and acute exacerbation of inflammatory processes in the periodontium might be a trigger for the event of cerebral ischemia.

Adolescent↗
PubMed2003

Platelet function under aspirin, clopidogrel, and both after ischemic stroke: a case-crossover study.

BACKGROUND AND PURPOSE: Combined antiplatelet agents may offer additive protection over single drugs after stroke. We investigated whether platelet activation is reduced under combined aspirin and clopidogrel compared with each drug alone. METHODS: In a case-crossover study, 31 patients with previous atherothrombotic or lacunar stroke who were treated with aspirin (100 to 300 mg/d) received clopidogrel (75 mg/d) and both aspirin and clopidogrel for 4 weeks. Platelet function in whole blood was studied after each treatment period and in healthy control subjects to assess activation-dependent antigens CD62p and CD63 by flow cytometry and collagen/epinephrine (CEPI-CT) and collagen/ADP (CADP-CT) closure times with the platelet function analyzer PFA-100, which investigates platelet-related function under shear stress. RESULTS: CD62p expression and CD63 expression were not different under the 3 treatment regimens. CD63 but not CD62p expression was lower in control subjects than in stroke patients regardless of the antiplatelet treatment (P<0.05). CEPI-CT was prolonged under aspirin and aspirin plus clopidogrel compared with clopidogrel monotherapy (P<0.0001). CADP-CT was longer under combination therapy than under aspirin (P=0.0009) or clopidogrel (P=0.0074) or in control subjects (P=0.0010), mainly because of strong prolongation in a patient subgroup (28%). CONCLUSIONS: CD63 expression reflecting the release of platelet lysosomes is consistently increased after stroke and incompletely suppressed by treatment with aspirin, clopidogrel, or both. The strong prolongation of CADP-CT under combined aspirin and clopidogrel in a patient subgroup may indicate a lower risk of thrombosis but also a higher risk of hemorrhage. The predictive value of platelet activation parameters requires investigation in prospective studies.

Antigens, CD↗
PubMed2002

Lack of evidence for pulmonary venous thrombosis in cryptogenic stroke: a magnetic resonance angiography study.

BACKGROUND: Even after extensive evaluation, the etiology of ischemic stroke remains undefined in a considerable proportion of cases, suggesting that causes of stroke may exist that have not yet been established. We tested the hypothesis that pulmonary venous thrombosis (PVT) is a potential source of brain embolism in patients with cryptogenic stroke. SUMMARY OF REPORT: Within 7 days after mild to moderately severe ischemic stroke or transient ischemic attack, 18 patients (9 women, 9 men; mean age, 48 years) were studied in whom the etiology remained undefined despite complete workup. All patients received high-resolution pulmonary venography with the use of multiple-bolus, multiphase, 3-dimensional, gadolinium-enhanced MR angiography (MRA). Overall quality of the MRA was good in 14 and insufficient in 4 patients, mainly as a result of breathing artifacts. Visualization of the main and segmental veins and evaluability of their patency were good for most right pulmonary veins but often inadequate for left pulmonary veins, particularly for those in the left lower lobe. There was no evidence for PVT in any of the sufficiently visualized pulmonary veins. CONCLUSIONS: The results do not support the hypothesis of PVT as a contributor to the etiology of ischemic stroke. However, the study was limited regarding scan volume, spatial discrimination, patient selection, and delay between ischemia and MRA. Therefore, further investigations, including postmortem studies, are needed to resolve the question of whether PVT may contribute to ischemic stroke.

Adult↗
PubMed2002

New method of embolus preparation for standardized embolic stroke in rabbits.

BACKGROUND AND PURPOSE: Although thromboembolic stroke is caused by red, white, or mixed clots, the emboli previously used in animal studies on thrombolysis were more often red than white. Because this might be one of the reasons why thrombolysis is less effective in patients than in experimental stroke, we developed a new method of preparing highly standardized red and fibrin-rich white emboli. METHODS: The middle cerebral artery of 20 rabbits was embolized with either red or fibrin-rich white autologous emboli. Cerebral perfusion was monitored by MRI. RESULTS: Red emboli consisted of closely packed erythrocytes within a sparse fibrin net and white emboli of a dense mass of fibrin with only few other blood cells. Infarct volumes were 26+/-4% (mean+/-SD) of the ischemic hemisphere with red and 27+/-6% with white emboli. The relative regional cerebral blood volume dropped below 50% 90 minutes after vascular occlusion with either type of embolus. Late spontaneous lysis and hemorrhagic complications occurred in 37.5% of red but not in white embolus cases. CONCLUSIONS: Emboli prepared by our technique result in standardized cerebral infarctions. Size and composition of the emboli continuously can be adjusted according to the experimental requirements.

Angiography, Digital Subtraction↗