XVII. European Stroke Conference
Nice, France
XVII. European Stroke Conference
Nice, France
Poster Session:
Stroke and infections
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
Asymptomatic T2* cerebral microbleeds in infective endocarditis
E. Auffray-Calvier
L Le Hénaff
B Daumas-Duport
P Derkinderen
A Bammert
D Crochet
A de Kersaint-Gilly
H Desal
CHU-Nantes
FRANCE
Background and Purpose. Cerebral microbleeds on T2-gradient recall echo imaging (T2*GR) have numerous origins. Our purpose was to evaluate the usefulness of T2*GR for cerebral imaging in infectious endocarditis population without neurological symptom. Methods. Two groups were studied. Nineteen patients with infective endocarditis (mean age (+/-SD), 55 years+/- 20) and 19 healthy control subjects underwent T2* GR. The incidence of "black holes", topography and number was evaluated by 2 neuroradiologists. Presence of prosthetic heart valves, in two groups, was noted. Results. Asymptomatic T2* cerebral microbleeds were significantly (p<.001) more common in patients (19/19) when compared with controls (5/19). In patients, microbleeds were significantly higher in sub-cortical white matter (100%) than in basal ganglia (42%) and brain stem (5%). There were more microbleeds in patients with prosthetic heart valves. In the patient group, 10/19 had prosthetic heart valves, while in controls with cerebral "black holes" 4/5 had prosthetic heart valves. Conclusion. Asymptomatic T2* cerebral microbleeds are new and common findings in infective endocarditis. We should be aware of these common findings and not mistake them for more commonly recognized causes of microbleeds (amyloid angiopathy, chronic hypertension and multiple cavernoma syndromes)
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
Human stroke promotes an anti-inflammatory phenotype on monocytes with expansion of CD14++CD16+ monocytes
X. Urra
A. Cervera
N. Villamor
A.M.Planas
A. Chamorro
Hospital Clínic Barcelona
SPAIN
Background. Stroke may increase the number of circulating monocytes but their phenotype and function is unknown. We sought to study monocyte subpopulations and their phenotype after human stroke. Methods. Flow cytometry was serially used in 12 healthy controls and in 42 stroke patients to assess monocyte subpopulations including classical CD14++CD16-, resident CD14dimCD16+ (strong producers of TNF-a) and mixed CD14++CD16+. Surface expression of HLA-DR, co-stimulatory CD86, scavenger receptor CD163, proangiogenic angiopoietin 2 receptor Tie-2, and intracellular production of TNF-a and IL-10 after lypopolisacharide stimulation (LPSE) were correlated with clinical course (NIHSS score), incidence of infections, and modified Rankin Scale (mRS) at 3 months. Results. Overall, stroke resulted in increased count of monocytes (p=0.03) characterized by a reduction of CD14dimCD16+ (p<0.001) and an increase of CD14++CD16+ (p<0.001) which expressed the highest levels of CD163 and Tie-2. Stroke was followed by a decrease of HLA-DR (P<0.001) and a reduced production of TNF-alpha (p=0.001) but not IL-10. These findings predominated in the 14 patients who developed infections, who also had lower levels of CD86 (p=0.04). Decreased production of IL-10 after LPSE was associated with poorer mRS (p=0.04). Discussion. Ischemic stroke drives a monocytic response characterized by an anti-inflammatory phenotype and promotion of tissue repair and angiogenesis. Whereas this response may favour the appearance of infection it is associated with increased neurological recovery.
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
RECENT INFECTIVE OR INFLAMMATORY EVENT MIGHT AFFECT OUTCOME IN PATIENTS WITH ACUTE ISCHEMIC STROKE TREATED WITH INTRAVENOUS THROMBOLYSIS.
M. Nesi
P. Nencini
G. Pracucci
D. Inzitari
D. Consoli
on behalf of the INDUE collaboration
University of Florence, Jazzolino Hospital, Vibo Valentia
ITALY
Background: Inflammation plays a key role in relation to acute stroke pathology, and infective or inflammatory events may act as precipitators of ischemic stroke. Biological factors linked with inflammation (for example, metalloproteinases) seem to be implicated with hemorrhagic transformation after intravenous rtPA treatment. Whether infections or inflammatory events occurring before stroke may influence the outcome after rtPA treatment is unknown. Methods: from March 2003 to June 2007, 709 patients with acute stroke ischemic stroke were enrolled in the INDUE study, an Italian prospective study designed to evaluate the role of infective or inflammatory events, occurred within 30 days prior to stroke, as potential determinants of stroke outcome. Results: of the whole INDUE series 64 patients (male 54.7%, mean age 67 years, mean NIHSS 11) were treated with rtPa administered in 3 hours from symptoms onset. Out of these 64 patients, 10 (15.6%) turned out to have had an infective or an inflammatory event prior to stroke. A recent infection, particularly with fever, significantly and independently (65% versus 6.7%, p 0.002 adjusted for major determinants) increased the risk of neurological worsening during hospitalization (NIHSS ≥1) and the risk of death (50% vs 5%, p= 0.001). No effect of infection was observed related to hemorrhagic complication after thrombolysis (7.5% versus 18.2%, p=0.271) Conclusion: we suggest that in patients with acute stroke undergoing rtPA treatment, a recent infection occurring prior to stroke, may influence early clinical outcome. Our observation merits corroboration by larger studies.
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
Single nucleotide polymorphisms in the toll-like receptor 4 gene are not associated to infection risk or prognosis after stroke
M. Vargas
A. Cervera
X. Urra
S. Amaro
M. Gomez-Choco
V. Obach
A.M.Planas
F. Lozano
A. Chamorro
Stroke Unit, Hospital Clinic, IDIBAPS
SPAIN
Background and Purpose: Toll-like receptor 4 (TLR-4) is a crucial component of the innate immune response and its deficiency has been related to better outcome in animal models of focal cerebral ischemia-reperfusion. In this study we investigated whether single nucleotide polymorphisms (SNP) in the TLR4 gene were associated with the functional outcome, risk of infection and humoral innate system response that followed acute stroke. Methods: SNP of the TLR4 gene were assessed in 135 acute stroke patients included in the ESPIAS trial that evaluated the efficacy of antibiotic prophylaxis (levofloxacin vs. placebo) in the prevention of early infection after stroke. The number of neutrophils, monocytes, and lymphocytes, and serum levels of C-reactive protein, TNF-alpha, IL-6, IL-10, C3, and C4 were monitored in blood samples collected at several points after stroke, and their values correlated with the genotype and main clinical findings. Multivariate analyses were used to adjust the effects of confounders. Results: Twelve (8.9%) patients had a SNP in the TLR4 gene. Serum concentration of C3 and C4, and the cytokine response were unrelated to the TLR4 genotype. The risk of stroke-associated infection (OR= 1.14, 95% CI 0.20-6.63) and poor outcome (OR= 0.87, 95% CI 0.22-3.46) was similar in patients with and without the SNP. Conclusion: Genetic variations in the TLR4 gene do not modify the functional outcome, risk of infection and humoral innate system response that followed acute stroke.
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
Genotypic variations in the lectin pathway of complement activation contribute to the prognosis of human stroke
A. Cervera
X. Urra
C. Justicia
S. Amaro
V. Obach
B. Suarez
A.M.Planas
F. Lozano
A. Chamorro
Hospital Clinic of Barcelona, IDIBAPS
SPAIN
Background and Purpose: Mannose-binding lectin (MBL) is a key component of the lectin pathway of complement activation. In this study we sought to investigate whether genetic variations within the lectin pathway were associated with the functional outcome, risk of infection and humoral innate system response that followed acute stroke. Methods: Gene polymorphisms of the MBL2 gene were assessed in 135 acute stroke patients included in the ESPIAS trial that evaluated the efficacy of antibiotic prophylaxis (levofloxacin vs. placebo) in the prevention of early infection after stroke. The number of neutrophils, monocytes, and lymphocytes, and serum levels of C-reactive protein (CRP), TNF-alpha, IL-6, IL-10, C3, and C4 were monitored in blood samples collected at several points after stroke, and their values correlated with the genotype and main clinical findings. Multivariate analyses were used to adjust the effects of confounders. Results: Twenty-four (17.8%) patients had a genetic MBL2 variant associated with low levels of MBL. Significantly lower concentrations of CRP, and C3 and C4 proteins of the complement system were observed in patients with MBL-low variants. The cytokine response was unrelated to MBL2 genotype. Logistic regression adjusted for age and baseline stroke severity identified MBL-low variants associated with a modified Rankin Scale score 0 to 2 (OR=3.46, 95% CI 1.08-11.10), but not with an increased risk of infection (OR=1.27, 95% CI 0.42-3.84). Conclusion: Gene polymorphisms associated with MBL deficiency facilitate recovery after stroke without increasing the risk of infection. These results underscore the central role of the lectin pathway of complement activation for post-stroke injury.
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
Genomic response profile in cardiomyopathy and stroke associated with Chagas disease: A microarray analysis study
J. Oliveira-Filho
E.C.S.Camargo
L.M.B.Oliveira
I.S.N.Ribeiro
C.C.S.Santos
D.M.Fonseca
F.J.F.B.Reis
W.J.Koroshetz
B.M.Coull
K.L.Furie
Federal University of Bahia and Massachusetts General Hospital
BRAZIL
Background: Chagas disease (CD) is a chronic tropical disease that leads to cardiomyopathy (CM) and ischemic stroke. CD carries an independent odds-ratio for stroke, which may be due to atherothrombosis secondary to chronic inflammation. We aimed to assess if CD infection causes an increase in white blood cell (WBC) genomic response and if it alters the WBC genomic profile in stroke and CM. Methods: Whole blood was examined using oligonucleotide microarrays in 12 CD patients (4 with stroke, 8 with CM) and 21 CD- controls (15 with stroke, 6 with CM), at least 6 months after any thromboembolic event, in the absence of active inflammation. Results: Genes induced in WBC were: a) for patients with CD: metastasis-associated lung adenocarcinoma transcript 1 was over-expressed (fold-change= 2.8). b) For patients with stroke and CD, over-expressed genes (fold change, 2.06 to 6.82) were: matrix metalloproteinase 9; membrane metallo-endopeptidase; arginase I; carbonic anhydrase IV; orosomucoid 1; cathelicidin antimicrobial peptide; contactin associated protein-like 3; napsin B aspartic peptidase pseudogene; hypothetical protein FLJ10357, and similar to HIV TAT specific factor 1. c) For patients with CM and CD, a differentially expressed gene was amiloride binding protein 1 (under-expressed, fold-change=2.4). Discussion: A variety of genes involved in angiogenesis, apoptosis and inflammation are differentially expressed in CD subgroups. These data provide insights into genomic responses in CD, and those specific to CD subjects that suffer a stroke or that have CM. Our results should help in understanding the pathophysiology of CD complications, and the development of diagnostic strategies and new treatments for cardiovascular complications of CD.
Session:
Poster Session I
Date:
Wednesday 14 May 2008
Time:
12:30 - 14:00
Room:
Agora 3
Chagas Disease Scan Study: Brain atrophy is not associated with brain infarcts
D.F.Menezes
C. Abbehusen
I.N.S.Ribeiro
C.C.S.Santos
P.A.P.Jesus
D.F.Pereira
A.M.Lacerda
L.C.Viana
F.J.F.B.Reis
J. Oliveira-Filho
Federal University of Bahia
BRAZIL
Background: Chagas disease affects 18 million people in South America. Brain involvement is attributed to heart disease with secondary cardioembolic stroke. However, we have previously demonstrated that brain atrophy on head CT and cognitive impairment is more frequent in CD patients independently of cardiac disease severity. Our objective was to investigate the mechanisms of brain involvement using magnetic resonance imaging. Methods: Consecutive patients from a specialty Cardiomyopathy Clinic were enrolled. Echocardiographic inclusion criteria were an ejection fraction (EF) < 40%, or an EF=41-49% with a dilated left ventricle. Patients with a history of stroke were excluded. Axial T1, T2 and FLAIR sequences were evaluated by a radiologist blinded to clinical data, scoring degree of brain atrophy (0-9 in three brain regions on a visual analog scale), white matter disease (0-3) and number of brain infarcts. Results: Twenty-six patients were enrolled from March to December, 2007. Ten (38%) patients had CD cardiomyopathy and the remaining had other cardiomyopathy (OC) etiologies, mainly hypertensive, ischemic or dilated idiopathic. Age was well balanced between groups (55 for CD and 53 for OC patients, p=0.577). Degree of cardiac involvement was also similar (EF=34.2% in CD, 31.8% in OC, p=0.537). Brain atrophy was more pronounced in CD patients (2.7 +/- 1.8) when compared with OC patients (1.5 +/- 1.6), with borderline statistical significance (p=0.064). The mean number of brain infarcts was similar in both groups (0.8 in CD vs. 0.5 in OC, p=0.969). Discussion: Chagas disease seems to be associated with brain atrophy that is independent of cardiac disease severity or the presence of cardioembolism. Active brain or systemic inflammation should be investigated as possible mechanisms of brain involvement in patients with CD.
