XVII. European Stroke Conference
Nice, France

Oral Session:

Stroke and infections
Date: Wednesday14 May 2008  
Time: 8:30 - 8:40 -  Room: Erato/Uranie
Chair: A. Czlonkowska, Poland and A. Lindgren, Sweden

01
Infectious Burden and Risk of Stroke: The Northern Manhattan Study
M.S.Elkind    Y.P.Moon    K. Liu    H. Wang    I. Singh    T. Rundek    R.L.Sacco    M.C.Paik              
 

Columbia University

USA

Background: Common infections, such as Chlamydia pneumoniae (Cp) and CMV, may be associated with stroke risk. No one infection is likely to be a major independent predictor of stroke (i.e., a “stroke bug”). More likely is that overall burden of prior infections contributes to risk. We assessed the association between serologies to common infections and stroke risk in a prospective cohort study. Methods: Stroke-free participants were identified by random-digit dialing. Antibody titers to Cp, H. pylori, CMV, HSV 1 and HSV 2 were measured in blood samples from study entry. Cox proportional hazards models were used to calculate parameter estimates for association of each infection with stroke. Individual unadjusted parameter estimates were then combined into a weighted index of infectious burden (IB) which was used as the independent variable to calculate hazard ratios and confidence intervals (HR, 95%CI) for association of infectious burden with risk of stroke and other outcomes, adjusted for other risk factors. Results: All five infectious serologies were available in 1625 participants (mean age 68.5+/- 10.1 years; 64.9% women; median follow-up 8 years). Each individual infection was positively, though not significantly, associated with stroke risk after adjusting for risk factors, with HR from 1.13 for H. pylori to 2.19 for CMV. The overall index of IB had a mean of 1.00+/-0.33, median 1.08. IB was associated with an increased risk of all strokes (HR 2.69, 95%CI 1.04-6.92) after adjusting for demographics, blood pressure, coronary disease, waist size, alcohol consumption, physical activity, smoking, glucose, HDL, and LDL. There was an increased risk with IB for a composite outcome of stroke, MI, and death (adjusted HR 1.53, 95%CI 1.09-2.14), but not for MI alone (HR 1.18, 95%CI 0.60-2.33). Conclusion: A quantitative weighted index of infectious burden was associated with risk of first stroke in this cohort. Future studies are needed to confirm these findings and to further define optimal measures of IB as a vascular risk factor.

Stroke and infections
Date: Wednesday14 May 2008  
Time: 8:40 - 8:50 -  Room: Erato/Uranie
Chair: A. Czlonkowska, Poland and A. Lindgren, Sweden

02
Ischemic Stroke Outcome at 90 Days depends on the Extent of Early Inflammation
H. Worthmann    A.B.Tryc    A. Goldbecker    Y. Ma    A. Tountopoulou    R. Dengler    R. Lichtinghagen    K. Weissenborn              
 

Medical School Hanover

GERMANY

BACKGROUND: Early inflammation has been identified as one of the predominant prognostic factors after acute ischemic stroke. A detailed correlation analysis between early inflammatory reaction and clinical outcome, however, is still lacking. Recently, we were able to show an interrelationship between inflammation biomarkers and short term outcome in stroke patients. This paper compares the functional outcome after three months with the time course of selected biomarkers (TIMP-1, MMP-9, IL-6, CRP, MCP-1, S-100) after ischemic stroke. METHODS: After informed consent blood samples and functional scores (mRS, NIHSS) were taken at 3 to 6h, 12h, 24h, 3d, 7d, and 90d after symptom onset in 52 stroke patients. Plasma/ serum concentrations of selected biomarkers were measured by commercially available immuno-assays. RESULTS: TIMP-1, MMP-9, IL-6, CRP, MCP-1, and S-100 showed significantly different time courses depending on stroke severity at day 7 and 90. Plasma levels of TIMP-1, IL-6, CRP, and MCP-1 correlate negatively with clinical outcome at day 90 (TIMP-1: 12h: r=0.401; p<0.023; 24h: r=0.558; p<0.001; 3d: r=0.610; p<0.001). S-100 levels correlate at each time point except for 90d but particularly at 24h strongly with functional scores at day 1, 7, and 90 (day1: r=0.694; p<0.001; day7: r=0.692, p<0.001, day90: r=0.737, p<0.001). MMP-9, TIMP-1, and IL-6 increased as early as 3-6 hours after symptom onset whereas CRP levels showed a delayed maximum at 24 hours and 3 days after symptom onset. While MMP-9 and S-100 had decreased again at day 90, TIMP-1, MCP-1, IL-6, and CRP levels remained elevated at least in patients with severe stroke. DISCUSSION: Our data show a negative correlation between early plasma levels of inflammatory biomarkers - in particular TIMP-1, IL-6, CRP, and S-100 - and stroke outcome at 90d. Patients with full recovery in functional scores show a different time course of biomarkers compared to those with poor clinical outcome. Interestingly 90d after stroke significant differences in levels of TIMP-1, MCP-1, IL-6, and CRP depending on stroke severity are still detected.

Stroke and infections
Date: Wednesday14 May 2008  
Time: 8:50 - 9:00 -  Room: Erato/Uranie
Chair: A. Czlonkowska, Poland and A. Lindgren, Sweden

03
Symptomatic carotid plaque inflammation is more intense following TIA than completed stroke - evidence from FDG PET
R.R.Moustafa    D. Izquierdo-Garcia    T.D.Fryer    M.J.Graves    J.H.Gillard    P.L.Weissberg    J.C.Baron    E.A.Warburton              
 

University of Cambridge

UNITED KINGDOM

BACKGROUND: Histologic studies suggest that symptomatic carotid artery plaques associated with TIA undergo surface erosion yet remain structurally intact, whereas plaques associated with completed stroke are likely to have acutely ruptured. This difference may be reflected in residual plaque inflammation detected by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). METHODS: 16 patients presenting with recent (46.6 +/-31 days) anterior circulation TIA or minor stroke and stenosis of the ipsilateral carotid (40-99%) underwent FDG PET and high-resolution black-blood MRI of the neck and chest,. ROIs drawn on the co-registered MRI were used to calculate plaque volume and transferred onto PET images to measure maximum Standard Uptake Values (SUVmax) for the ipsilateral and contralateral carotid plaques, and venous blood pool. Partial volume correction (Rousset method) was applied to improve quantification. RESULTS: MRI identified atheromatous plaques in both carotid arteries in all patients (ipsilateral vs. contralateral carotid plaque volume: 1686+/-625 µL vs. 1118+/-563 µL, respectively; p<0.001), with weak correlation to the degree of stenosis on ultrasonography (r=0.12, p=0.6). There was no difference in ipsilateral carotid plaque volume whether patients presented with TIA (n=10; 63%) or stroke (p=0.8). No overall difference was found between FDG uptake in ipsilateral and contralateral carotid plaques (SUVmax 3.71+/-0.97 vs. 3.68+/-0.84, respectively; p=0.8), yet patients presenting with TIA were significantly more likely than those presenting with stroke to have higher FDG uptake in the ipsilateral carotid plaque than in the contralateral carotid plaque (ipsilateral>contralateral, 70% vs. 16% for TIA and stroke respectively; p=0.039). CONCLUSION: Recently symptomatic carotid atheroma associated with ipsilateral TIA continues to show relatively more intense inflammatory activity than contralateral carotid atheroma, yet this relationship appears reverted in completed stroke, suggesting varying dynamics of plaque pathophysiology.

Stroke and infections
Date: Wednesday14 May 2008  
Time: 9:00 - 9:10 -  Room: Erato/Uranie
Chair: A. Czlonkowska, Poland and A. Lindgren, Sweden

04
Infection after stroke does not increase platelet activation nor platelet-leukocyte interaction
M.J.Gómez-Choco    X. Urra    A. Cervera    J.C.Reverter    N. Villamor    A.M.Planas    A.  Chamorro                     
 

Hospital Clinic Barcelona

SPAIN

Background. Infections preceding stroke are associated to greater platelet activation and poor outcome. In this study we assessed whether platelet activation and platelet-leukocyte interactions differ in patients with infection after stroke. Methods. In 32 patients with no precedent infection admitted in 4 hours (range 2-12) after ischemic stroke we assessed clinical severity (NIHSS), lesion volume (DWI at day 1), incidence of infections and modified Rankin Scale (mRS) at 3 months. We measured P-selectin and CD40 ligand (CD40L) surface expression in platelets and the proportion of platelet-neutrophil (PNC) and platelet-monocyte (PMC) complexes at day 0, 2, 7 and 90 using flow cytometry. Ten age-matched healthy subjects served as controls. Results. P-selectin, PNC, and PMC, but not CD40L were significantly increased in patients. DWI volume was directly correlated with P-selectin (r=0.66, p=0.001), and worse mRS at 3 months was also associated to greater P-selectin (p=0.01). Eleven (34%) patients developed infection and those had higher NIHSS score at baseline and greater mRS at 3 months. Platelet surface expression and platelet-leukocytes complexes were not associated to the risk of infection nor changed once infection supervened. Discussion. Platelet surface expression and interaction with leukocytes is increased after acute ischemic stroke and correlated with the extent of damage. However, these markers of platelet signalling capacity are unrelated to the risk of post stroke infection and do not change significantly if infection supervenes. Overall, these findings confirm the relevance of platelets after stroke but suggest a different role of hemostasis in the infections that follow or precede acute ischemic stroke.

Stroke and infections
Date: Wednesday14 May 2008  
Time: 9:10 - 9:20 -  Room: Erato/Uranie
Chair: A. Czlonkowska, Poland and A. Lindgren, Sweden

05
Low oxygen saturation is a risk factor for poor outcome in patients with stroke associated infection.
F.H.Vermeij    W.J.Scholte op Reimer    P. de Man    P.J.Koudstaal    D.W.Dippel                                   
The Netherlands Stroke Survey Investigators

Erasmus Medical Center

THE NETHERLANDS

Objectives: Infections that occur within 7 days after acute ischemic stroke have been found to be independently associated with poor outcome. It is unknown whether this association is causal, and which aspects of infectious disease play a role. We aimed to assess which aspects of infection are associated with poor outcome. Methods: In a consecutive multicenter cohort of 521 patients 78 (15%) developed a stroke associated infection (SAI), defined according to the CDC criteria, occurring within 7 days after stroke onset. We collected data on the characteristics of SAI, including low oxygen saturation (LOS) defined as oxygen saturation lower than 95%, or a persistent requirement for oxygen treatment, and stroke related prognostic factors. Poor outcome at discharge and at 1 year was defined as a modified Rankin scale score>3. Relative risk estimates were adjusted for potential confounders by means of multiple logistic regression. Results: Forty-seven patients with SAI (60%) had a poor outcome at discharge, and 16 (21%) had died. Pneumonia occurred in 39 (50%), urinary tract infection in 23 (29%). Thirty-nine patients (50%) had an episode of LOS, of whom 32 (82%) had poor outcome at discharge. Pneumonia and LOS occurred in 27 patients. In patients with LOS the relative risk of poor outcome was 2.1 (95% CI 1.4-3.3) at discharge, and 1.4 (95% CI:1.0-1.8) at 1 year. Adjustment for age and stroke severity did not affect these estimates. Discussion and conclusion: Low oxygen saturation in patients with stroke associated infection is a risk factor for poor outcome after acute ischemic stroke. Treatment and prevention of conditions causing low oxygen saturation are a potential target for improvement of outcome after stroke.

Stroke and infections
Date: Wednesday14 May 2008  
Time: 9:20 - 9:30 -  Room: Erato/Uranie
Chair: A. Czlonkowska, Poland and A. Lindgren, Sweden

06
Infectious Burden and Carotid Plaque Thickness: The Northern Manhattan Study
M.S.Elkind    Y.P. Moon    K. Liu    H. Wang    I. Singh    B. Boden-Albala    R.L.Sacco    M.C.Paik    T. Rundek       
 

Columbia University

USA

Background: Common infections, such as Chlamydia pneumoniae (Cp) and CMV, may be associated with atherosclerosis. No one infection, however, is likely to be a major independent cause of stroke (i.e., “stroke bug”). More likely is that overall burden of prior infections contributes to vascular disease. We assessed the association between serologies to common infections and carotid plaque thickness in a multi-ethnic cohort. Methods: A cross-sectional study was performed among stroke-free community participants. Antibody titers against Cp, H. pylori, CMV, HSV 1, and HSV 2 were measured, and a weighted index of infectious burden (IB) was calculated based on the individual parameter estimates derived from Cox models for the association of each infection with stroke risk. High-resolution duplex Doppler was used to assess maximum carotid plaque thickness (MCPT). Multivariable linear regression was used to calculate magnitude of association between IB and MCPT after adjusting for risk factors. Results: All five infectious serologies were available in 861 participants with MCPT measurements available (mean age 67.2+/-9.6 yrs). Each individual infection was positively, but not significantly, associated with stroke risk after adjusting for other risk factors. The IB index (n=861) had a mean of 0.99 + 0.35, median 1.08. Plaque was present in 52% of participants (mean 1.7+/-0.8 mm). Each unit increase of IB was associated with an MCPT increase of 0.27, 95%CI 0.08-0.44 mm (p=0.0056), after adjusting for demographics, smoking, diabetes, coronary disease, blood pressure, and lipids. Conclusion: In this multi-ethnic cohort, a quantitative weighted index of infectious burden, derived from the magnitude of association of individual infections with stroke, was associated with MCPT. These results support the notion that past exposure to common infections, perhaps by exacerbating inflammation, contributes to atherosclerosis. Future studies are needed to confirm these findings and to define optimal measures of infectious burden as a vascular risk factor.