XVII. European Stroke Conference
Nice, France

Oral Session:

Intracerebral and subarachnoid bleedings/ Cerebral haemorrhage and SAH
Date: Friday 16 May 2008  
Time: 8:00 - 8:10 -  Room: Clio/Thalie
Chair: A. Demchuk, Canada and C. Stapf, France

01
Risk of subarachnoid haemorrhage according to number of affected first degree relatives: a population-based study in Sweden.
S. Bor    G.J.E.Rinkel    J. Adami    H. Koffijberg    A. Ekbom    E. Buskens    P. Blomqvist    F. Granath              
 

Institute: Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht

THE NETHERLANDS

Background: Relatives of patients with aneurysmal subarachnoid haemorrhage (SAH) have an increased risk of SAH. In a population-based study we analysed individualised risks of SAH according to the number of affected first degree relatives. Methods: From the Swedish Inpatient Register we retrieved all patients diagnosed with SAH in 2001-2005. For each of the 5282 patients we identified 5 controls (total 26402) through the nationwide Register of Total Population. Through the Multi-generation Register we retrieved all first degree relatives for patients and controls, and checked whether these 130373 relatives had been diagnosed with SAH. By means of conditional logistic regression, we calculated odds ratio’s (OR’s) with corresponding 95% confidence intervals (CI’s) for the risk of SAH according to the number of affected relatives, and to the gender, age and type of kinship of the patient and affected relative. Results: The OR of SAH for individuals with one affected first-degree relative was 2.15 (95%CI 1.77-2.59). For individuals with two affected first-degree relatives OR was 51.0 (95%CI 6.53-399) and the absolute life-time risk of SAH 26%. Gender, age, and type of kinship did not influence the risk of SAH for individuals with one or more affected relatives. Discussion: The risk of SAH is slightly increased in case of one, but strongly increased in case of two or more affected first-degree relatives. The strongly increased risk in case of two affected relatives corresponds to a considerable absolute life-time risk of SAH, and underscores the need to consider screening for aneurysms in these individuals.

Intracerebral and subarachnoid bleedings/ Cerebral haemorrhage and SAH
Date: Friday 16 May 2008  
Time: 8:10 - 8:20 -  Room: Clio/Thalie
Chair: A. Demchuk, Canada and C. Stapf, France

02
Hemorrhagic forms of reversible cerebral vasoconstriction syndrome
A. Ducros    U.  Fiedler    M. Boukobza    D. Valade    M.G.Bousser                                   
 

Lariboisiere Hospital, APHP

FRANCE

Objective: To describe the patterns of intracerebral hemorrhage in reversible cerebral vasoconstriction syndrome (RCVS). Background: RCVS is characterized by severe headaches and a string and beads appearance on cerebral arteries, which resolves spontaneously in 1-3 months. We recently showed (Brain 2007;130:3091-101) that the most frequent complication is cortical subarachnoid hemorrhage (cSAH). Design/Methods: From January 2004 to January 2008, we prospectively recruited 89 consecutive patients with angiographically proven RCVS of whom 30 (27 females, 3 males, mean age: 46.5 years) had at least one variety of intracranial hemorrhage. Results: RCVS was spontaneous in 13 of the 30 patients (43%), and secondary to postpartum in 5 (18% of women) and to exposure to vasoactive substances in 12 (48% of the sample excluding postpartum cases), mainly selective serotonin-recapture inhibitors (9), nasal decongestants (3) and cannabis (2). Three types of hemorrhages were found: cSAH (27 patients), intracerebral hemorrhage (ICH) (11) and subdural hemorrhage (SDH) (2). Various combinations were observed: cSAH with ICH (7 patients), cSAH with SDH (1), and cSAH with SDH and ICH (1). Four patients also developed an ischemic stroke. The main pattern of presentation was recurrent thunderclap headaches over one week (83%), however 5 patients had only a single thunderclap. Nine patients had an acute focal neurological deficit. Other complications were seizures (3 patients), reversible posterior leukoencephalopathy (5) and TIAs (6). Initial angiogram (by MR, CT or conventional) was normal in 23% of patients in which vasoconstriction was visible only on a second angiogram performed a few days later. All patients received nimodipine. Five patients (17%) could not resume work due to permanent neurological impairement. Conclusions/Relevance: RCVS should be considered in all patients with cryptogenic non aneurismal, non traumatic cSAH, ICH or SDH. Diagnosis may be difficult during the first week and requires the repetition of cerebral angiogram.

Intracerebral and subarachnoid bleedings/ Cerebral haemorrhage and SAH
Date: Friday 16 May 2008  
Time: 8:20 - 8:30 -  Room: Clio/Thalie
Chair: A. Demchuk, Canada and C. Stapf, France

03
Rapid reversal of anticoagulation using Prothrombin Complex Concentrate reduces hemorrhage volume and improves outcome in a mouse model of Warfarin-associated intracerebral hemorrhage
C. Foerch    K. Arai    K. van Leyen    E.H.Lo                                          
 

Neuroprotection Research Lab Massachusetts General Hospital Harvard Medical School Charlestown, MA USA

USA

Background: Warfarin-associated intracerebral hemorrhage (W-ICH) is a severe type of stroke with a short-term mortality rate of up to 50%. There is no widely accepted consensus on the optimal treatment for W-ICH, and there are no randomized clinical trials to provide guidance. We recently developed a mouse model of W-ICH. Using this model, the present study was performed to test whether treatment with human Prothrombin Complex Concentrate (PCC) can reduce hemorrhage volume and improve outcome in W-ICH. Methods: Male CD-1 mice were treated with Warfarin (2mg/kg body weight) via drinking water, resulting in mean INR values of 3.5+/-0.9 after 24 h. In a first set of animals, i.v. administration of PCC (Beriplex, CSL Behring; 100 U/kg body weight) was shown to rapidly reverse anticoagulation. A second set of animals was used to test the efficacy of PCC in W-ICH. After surgically preparing the right jugular vein without opening the vessel (day 1) and Warfarin treatment (day 2), W-ICH was induced via stereotactic injection of collagenase Type VII (0.075 U) into the right striatum (day 3). 45 min later, the jugular vein was re-exposed, and PCC or saline was injected (n=12 per group, blinded). Hematoma volume was quantified by means of photometric hemoglobin assay after 24h, and neurologic outcome was assessed on a 5-point scale. Results: All animals survived the first 24 h after hemorrhage induction. Hemorrhage volume was 4.2+/-2.4 mm3 in PCC-treated animals and 7.5+/-3.4 mm3 in placebo animals (p=0.011, t-test). The maximum hemorrhage volume was 7.0 mm3 in PCC-treated animals, whereas 7 of 12 placebo animals had even higher values. 5 of 12 PCC treated animals showed a favourable outcome after 24 h (i.e. slight deficits, no circling) compared to 0 of 12 placebo animals (p=0.012, chi-square test). Discussion: This study provides the first in vivo data identifying PCC to be an effective acute treatment for W-ICH by means of reducing hemorrhage volume and improving neurologic outcome. PCC treatment seems to be particularly capable to reduce the number of large and very large hematomas. The temporal profiles here suggest that PCC might work by ameliorating the acute expansion of hemorrhage. This model should also be useful for deeper dissection of the molecular mechanisms of W-ICH brain injury and the further testing of potential therapies for this serious stroke subtype.

Intracerebral and subarachnoid bleedings/ Cerebral haemorrhage and SAH
Date: Friday 16 May 2008  
Time: 8:30 - 8:40 -  Room: Clio/Thalie
Chair: A. Demchuk, Canada and C. Stapf, France

04
Biological effects of simvastatin in patients with aneurysmal subarachnoid hemorrhage
M.D.Vergouwen    M. Vermeulen    J.C.Meijers    B.A.Coert    J. Horn    T. van der Poll    E.S.Stroes    Y.B.Roos              
 

Academic Medical Center, University of Amsterdam

THE NETHERLANDS

Background Recently, several studies showed that statins decrease the incidence of vasospasm after subarachnoid hemorrhage (SAH) in patients already protected by nimodipine. Although the trials were not powered to detect differences in clinical outcome, the results were impressive since it was observed that patients treated with statins have a decreased incidence of delayed cerebral ischemia (DCI) after SAH and lower overall mortality rates. It is unknown how statins decrease the incidence of vasospasm and DCI after SAH. Methods We performed an exploratory, single center, prospective, randomized, double-blind, placebo-controlled trial. Patients were randomized for simvastatin 80 mg a day or placebo, and were treated until day 14 after SAH. Blood withdrawal and transcranial Doppler examination were performed before initiation of the study drug, and at days 4, 7, 10, 14 and 17 after SAH. Patient inclusion was finished in August 2007. Unblinding of the treatment code will be in February 2008. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN45662651. Results 32 patients were included. Mean age was 54 years, 63% of patients were women. Median Glasgow Coma Score at admission was 14 (range 5-15). In total, 3 patients (9%) had rebleeding, 11 patients (34%) DCI, and 10 patients hydrocephalus (31%). 8 patients (25%) had poor outcome 3 months after SAH. Primary outcome will be the effect of simvastatin on laboratory parameters of endothelial function, fibrinolysis, coagulation, and inflammation after aneurysmal subarachnoid hemorrhage. The analysis involves all randomized patients irrespective of duration of treatment, timing of coiling or surgery etc. (intention to treat principle). Secondary outcomes will be the occurrence of vasospasm after SAH as observed on transcranial Doppler examination, clinical signs of DCI, and outcome on the Glasgow Outcome Scale and AMC Linear Disability Scale (ALDS) 3 and 6 months after SAH. Conclusion Preliminary results will be presented at the conference.

Intracerebral and subarachnoid bleedings/ Cerebral haemorrhage and SAH
Date: Friday 16 May 2008  
Time: 8:40 - 8:50 -  Room: Clio/Thalie
Chair: A. Demchuk, Canada and C. Stapf, France

05
Clinical Equipoise in the Management of Unruptured Intracranial Aneurysms: Data from the International Study of Unruptured Intracranial Aneurysms
R.D.Brown, Jr.    J.C. Torner    I. Meissner    D.G. Piepgras    J.  Huston, III                                   
for the International Study of Unruptured Intracranial Aneurysms Investigators

Mayo Clinic, Rochester, MN

USA

Background and Purpose: The International Study of Unruptured Intracranial Aneurysms (ISUIA) is a large observational cohort study of patients with unruptured intracranial aneurysms (UIA). The natural history and management risk data from this study may be used to define a group of patients with UIA in whom clinical equipoise exists. These patients should be considered for a randomized clinical trial of treatment compared to conservative management. Methods: The NIH-sponsored ISUIA is a 61 center study of 5500 patients with UIA. The third phase of ISUIA has extended the follow-up for 4060 prospectively entered patients. Outcomes following endovascular or surgical treatment and with conservative management have been determined including neurological status and endpoints including intracranial hemorrhage, cerebral infarction, and death. All outcomes have been centrally adjudicated. Categorical analysis and logistic regression will be performed. Outcomes will be compared between conservative management and surgery or endovascular management intervention, and the categories of UIA for which clinical equipoise exists will be delineated. Results: The 4060 prospectively entered patients in ISUIA were followed during a mean of 7.2 years. The cohort includes 1692 patients managed conservatively, 1971 patients treated with surgical clipping, and 451 treated with endovascular management. The risk of aneurysmal hemorrhage and other adverse neurological outcomes or death was determined for anterior and posterior circulation site categories, and subdivided into several aneurysm diameter groupings. An analysis of the comparative risks of natural history and interventional management is being performed using the final follow-up data from the third phase of ISUIA. A summary of UIA for which treatment equipoise exists will be reported. Conclusions: ISUIA data may be used to clarify UIAs for which clinical management equipoise exists. These aneurysms should be included in a randomized clinical trial of UIAs.

Intracerebral and subarachnoid bleedings/ Cerebral haemorrhage and SAH
Date: Friday 16 May 2008  
Time: 8:50 - 9:00 -  Room: Clio/Thalie
Chair: A. Demchuk, Canada and C. Stapf, France

06
HMG-CoA Reductase Inhibitors are associated with an increased intracerebral hemorrhage volume and may contribute to hemorrhage’s progression.
G. Ricard    M.P.Garant    J.M.Boulanger                                                 
 

Department of Neurology, University of Sherbrooke, Canada

CANADA

BACKGROUND: Some studies have suggested an association between hypocholesterolemia and the incidence of intracerebral hemorrhage (ICH). In a post hoc analysis of the SPARCL trial HMG-CoA reductase inhibitors use increased ICH risk. Accordingly, we tested the hypothesis that use of statin agents affects the volume of spontaneous ICH and contributes to the progression of ICH volume between baseline and follow up CT scans. METHODS: Consecutive cases of spontaneous ICH were reviewed. Secondary causes were excluded. We measured ICH volume on the baseline and follow up CT scans using the AxBxC/2 method. Multivariate analysis and logistic regression modeling were used. The primary outcome was the ICH volume on the baseline CT scan and the secondary outcome was the volume variation between the baseline and second CT scans. RESULTS: Of 303 subjects, 71 were taking a statin at the time of the ICH (23%). Compared with non-statin users, statin users were more likely to be younger (p=0.01), to have a history of coronary heart disease (p<0.001), hypertension (p=0.02), dyslipidemia (p<0.001), diabetes (p=0.02), and to take anticoagulant (p=0.001), anti-platelet (p<0.001), and anti-hypertensive medication (p<0.001). Compared to non-statin users, statin users had a higher ICH volume (mean 51.5 vs 35.2 ml; p=0.027). In the multivariate analysis, adjusting for anticoagulant, anti-platelet medication and others risk factors, statin remained associated with an increased ICH volume (p=0.007). There was a trend in ICH volume progression between the first and second CT scans (+10.3 vs -1.2 ml; p=0.064). Interval between CT scans was lesser than 72 hours in 65% of cases. History of hypertension (+3.9 vs -5.6 ml; p=0.033) and prior ICH (+23.5 vs -1.1 ml; p=0.004) were associated with a statistically different mean variation of volume. CONCLUSION: Treatment with HMG-CoA reductase inhibitors seems to be a risk factor for increased ICH volume in spontaneous brain hemorrhages and may contribute to hemorrhage’s volume progression. Prior ICH and hypertension also contribute to hemorrhage’s volume progression.

Intracerebral and subarachnoid bleedings/ Cerebral haemorrhage and SAH
Date: Friday 16 May 2008  
Time: 9:00 - 9:10 -  Room: Clio/Thalie
Chair: A. Demchuk, Canada and C. Stapf, France

07
Influence of Blood transfusion On Outcomes of Surviving Patients with Intracerebral Hemorrhage
K. Illoh    J. Lucke    O.C.Illoh                                                 
 

University of Texas Medical School, Houston, TX

USA

Background: Intracerebral hemorrhage (ICH) patients often receive blood products to treat coexisting anemia or bleeding disorders. Though blood products are thought to improve clinical outcomes, such transfusion has been associated with increased mortality. Among surviving patients, it is unclear how transfusion affects outcome. We sought to determine whether blood transfusion adversely affected outcomes of ICH patients who survived their inhospital stay. Methods: We analyzed the Nationwide Inpatient Sample (NIS) that comprised 20% of all admissions in the United States for patients hospitalized in the year 2003. We evaluated adult ICH patients who had mortality data available, and included those who survived their hospital stay (survivors). The differences in outcome between the transfused and nontransfused were determined. Our outcome measures were length of stay (LOS) and hospital charges. In a log-normal regression model, we determined if transfusion of red blood cells (RBCs) or nonRBC blood products (platelets, fresh frozen plasma, and coagulation factors) was an independent predictor of the outcomes while controlling for age, gender, race, and number of co-morbidities. Results: Of the 13,673 ICH patients, 9240 (68 %) were survivors with an average LOS of 10 days; 8% of the survivors (701/9240) received blood transfusion. Among these patients, the transfused group stayed in hospital longer (LOS, 15 +/- 17 days) compared to the nontransfused (LOS, 9 +/- 11 days). Likewise, transfusion was associated with 85% increase in hospital charges. Transfusion with RBCs significantly predicted LOS (p <0.0001) while nonRBCs did not (p = 0.97). Also, both RBCs (p <0.0001) and nonRBCs (p =0.0003) were independent predictors of hospital charges. Conclusion: Surviving ICH patients who received blood transfusion had longer hospital stay and remarkably higher cost of care. Further studies are warranted to determine if their functional outcome is similarly influenced as our findings maybe a reflection of their disease severity.

Intracerebral and subarachnoid bleedings/ Cerebral haemorrhage and SAH
Date: Friday 16 May 2008  
Time: 9:10 - 9:20 -  Room: Clio/Thalie
Chair: A. Demchuk, Canada and C. Stapf, France

08
Comparison of primary and arteriovenous malformation-related intracerebral haemorrhages in population-based studies
J. van Beijnum    C.E.Lovelock    C. Cordonnier    P.M. Rothwell    C.J.M.Klijn    R. Al-Shahi Salman                            
 

Division of Clinical Neurosciences, University of Edinburgh

THE NETHERLANDS

Background – Non-traumatic intracerebral haemorrhage (ICH) has a high case fatality and leaves many survivors disabled. Clinical characteristics and outcome seem to vary according to the cause of ICH, but rigorous population-based comparisons are scarce. Methods – We studied two prospective, population-based cohorts to determine differences in presenting features and outcome (case-fatality and modified Rankin Score [mRS]) after incident ICH due to brain arteriovenous malformations (AVM) (Scottish Intravascular Vascular Malformation Study [SIVMS], n=90) and primary ICH (Oxford Vascular Study [OXVASC], n=60). Results – Patients with AVM-ICH were younger, had lower pre-stroke and admission blood pressures (BP), higher Glasgow Coma Scores (GCS), and were more likely to have an ICH in a lobar location than patients with PICH. Case fatality throughout two-year follow-up was greater following PICH than AVM-ICH (34/48 [71%] versus 13/90 [13%] at 2 years, odds ratio [OR] 14 [95% Confidence Interval (CI) 6 to 34]), as was death or dependence (mRS  3) (38/42 [90%] versus 31/81 [38%], OR 15 [95% CI 5 to 47]). Differences in 2-year outcomes persisted following stratification by age (<60 versus ≥60). In multivariable analyses, independent predictors of death at 12 months were PICH (OR 16, 95%CI 3.1 to 80) and ICH volume (OR 1.03, 95% CI 1.01 to 1.05), and independent predictors of death or dependence at 12 months were PICH (OR 10, 95%CI 1.9 to 51), ICH volume (OR 1.03, 95% CI 1.00 to 1.05), non-lobar location (OR 3.0, 95%CI 1.5 to 6.3), and low GCS on admission (OR 0.79, 95% CI 0.63 to 0.88). Discussion – Outcome after AVM-ICH is better than after PICH, independent of patient age, and other known predictors of ICH outcome. Although better outcome after AVM-ICH may partially be due to under-diagnosis of AVM in patients with fatal ICH, it is unlikely to account fully for the observed differences in outcome.

Intracerebral and subarachnoid bleedings/ Cerebral haemorrhage and SAH
Date: Friday 16 May 2008  
Time: 9:20 - 9:30 -  Room: Clio/Thalie
Chair: A. Demchuk, Canada and C. Stapf, France

09
What Amount of Hematoma Enlargement is Clinically Relevant for Patients with Acute Intracerebral Hemorrhage?
J. Martí-Fàbregas    S. Martínez-Ramírez    E. Martínez-Hernández    M. Marquié    D. Alcolea    A. Vidal    M. Sáinz    I. Barroeta    R. Marín    J.-L.Martí-Vilalta
 

Hospital de la Santa Creu i Sant Pau

SPAIN

BACKGROUND Hematoma enlargement (HE) is the most frequent cause of neurological worsening (NW) during the acute stage of intracerebral hemorrhage (ICH). The usual definition is an increase ≥33% of ICH volume in the follow-up CT when compared to baseline CT. We determined the amount of HE that is best for predicting the extent of NW. METHODS We prospectively studied consecutive patients with single, spontaneous, supratentorial ICH, within the first 6 hours after the onset of symptoms. Using the formula AxBxC/2, we measured the hematoma volume on the admission CT (AVol) and on the follow-up CT (FVol). The percentage HE (HE%) was calculated according to the formula [(FVol-AVol):AV]x100). NW was defined as a decrease >1 point on the Glasgow Coma Score and/or an increase ≥4 on the NIHSS Score within the 24 hours after onset. Sensitivity, specificity, negative (NPV) and positive (PPV) predictive values. RESULTS We evaluated 60 patients (mean age 72.4 +/- 11 years, 58% were men ). Admission CT was obtained 143 +/- 73 minutes after the onset of symptoms; follow-up CT was obtained 29.3 +/- 9.9 hours after onset. Mean AVol was 20.3 +/- 24.3 ml, mean FVol was 32.3 +/- 43.7 ml, mean HE% was 95.2 +/- 234%. HE ≥ 33% was observed in 29 patients, and NW was observed in 21 patients (35%). HE% was greater in patients with NW than in patients without NW (23 +/- 93% vs 235 +/- 344%, p=0.001). A cut-off of HE%>46% had sensitivity of 85%, specificity of 82%, NPV of 91% and PPV of 71% to predict NW. A cut-off of HE% ≥33% had sensitivity of 85%, specifity of 72%, NPV of 90% and PPV of 62% in predicting NW. DISCUSSION Neurologic worsening is associated with a higher percentage of HE in the follow-up CT. A HE of 46% had the best predictive value.

Intracerebral and subarachnoid bleedings/ Cerebral haemorrhage and SAH
Date: Friday 16 May 2008  
Time: 9:30 - 9:40 -  Room: Clio/Thalie
Chair: A. Demchuk, Canada and C. Stapf, France

10
Multicentre Prospective Study Demonstrates Validity Of CTA “Spot Sign” For Hematoma Expansion Prediction in Noncoagulopathic Primary ICH Patients
A.M.Demchuk    M. Alzawahmah    J. Kosior    S. Tymchuk    C. Molina    I. Dzialowski    J.M.Boulanger    J. Roy    D. Gladstone    R. Aviv
PREDICT/Sunnybrook ICH CTA Study Group

University of Calgary

CANADA

Background: Better selection of ICH patients at risk for hematoma expansion is needed. Single centre ICH CT angiography (CTA) studies have detected small, enhancing foci (‘spot sign’) within acute hematomas which appear to predict ICH expansion. The PREDICT/Sunnybrook study is an ongoing prospective observational study that aims to determine the validity and feasibility of CTA based contrast extravasation to predict ICH expansion in a multicentre cohort. We present preliminary findings. Methods: ICH patients enrolled in study at 6 centres received acute CTA. Scans reviewed for “spot sign” by 3 blinded readers. ICH/IVH volumes quantified using computer assisted segmentation algorithm. Significant hematoma expansion defined as >5 ml increase in total hematoma volume (ICH+IVH). Results: 64 patients enrolled in study and all received baseline CTA. 21 patients (32%) demonstrated enhancing foci consistent with “spot sign”. Hematoma expansion analysis limited to 44 patients with normal INR and follow-up CT before rFVIIa or surgical intervention. Median onset-CTA time 201.5 minutes. Median baseline ICH volume was 23.7 ml for “spot sign” positive group and 9.2 ml for "spot sign" negative group (p=0.028). Significant hematoma expansion occurred in 8/44 patients (16%), all but one had a "spot sign" on CTA (p=0.0001). For significant hematoma expansion the positive predictive value for "spot sign" was 63% (7/11) and negative predictive value was 97% (32/33). Mean ICH volume expansion was 13.8 +/- 21.4 ml for "spot sign positive" cases and 0.0 +/- 5.1 ml for "spot sign" negative cases (p=0.0011). Mean IVH volume expansion was 13.4 +/- 27.0 ml for "spot sign" positive cases and 0.3 +/- 1.9 ml for "spot sign" negative cases (p=0.0069). Conclusions: The data validates the CTA “spot sign” as a strong predictor of intraparenchymal and intraventricular hematoma expansion. "Spot sign" negative patients are at very low risk for significant hematoma expansion. A clinical trial selecting ICH patients for hemostatic therapy using CTA "spot sign" appears warranted.

Intracerebral and subarachnoid bleedings/ Cerebral haemorrhage and SAH
Date: Friday 16 May 2008  
Time: 9:40 - 9:50 -  Room: Clio/Thalie
Chair: A. Demchuk, Canada and C. Stapf, France

11
An experimental model of Warfarin-associated intracerebral hemorrhage
C. Foerch    K. Arai    K. van Leyen    E.H.Lo                                          
 

Neuroprotection Research Lab Massachusetts General Hospital Harvard Medical School Charlestown, MA USA

USA

Background: Future demographic changes will increase the number of patients with atrial fibrillation. In parallel, long term anticoagulation for the prevention of ischemic strokes will gain in importance, and the burden of Warfarin-associated intracerebral hemorrhage (W-ICH) is likely to grow. Little is known about the clinical and pathophysiological aspects of W-ICH. The goal of this study is to develop a reliable mouse model of W-ICH, and use it to investigate the relationship between the level of anticoagulation, hematoma volume and neurologic outcome. Methods: CD-1 mice were treated with Warfarin (2mg/kg body weight per 24h) via drinking water. Intracerebral hemorrhage was induced via stereotactic injection of collagenase Type VII (0.075 U) into the right striatum. Hematoma volume was quantified with a calibrated hemoglobin assay at 2 and 24 h after hemorrhage induction. Outcome was assessed using a 5-point neurologic scale. Results: The international normalized ratio (INR) in non-anticoagulated mice (P) was 0.8+/-0.1. After 24 h (W-24) and 30 h (W-30) of Warfarin treatment, INR values increased to 3.5+/-0.9 and 7.2+/-3.4 respectively. Regardless of treatment group, no hemorrhage was observed in any of the sham-operated animals. All collagenase-injected mice showed the presence of a hematoma in the striatal area. As compared to P mice, hematoma volume at 24 h after hemorrhage induction was 2.5-fold larger in W-24 mice (p=0.019) and 3.1-fold larger in W-30 mice (p<0.001, n=10 per group). Mortality at 24 h was 0% in P mice, 10% in W-24 mice and 30% in W-30 mice. Hematoma enlargement between 2 to 24 h after hemorrhage induction was -1.4% for P mice, +22.9% for W-24 mice and +62.2% for W-30 mice. Discussion: This study characterizes the first experimental model of W-ICH. Anticoagulation with INR-values within the therapeutic range used in humans resulted in a 2.5-fold increase of hematoma volume in brain. W-ICH appears to progress over several h post-ictus, suggesting that there might be a potential time window for hemostatic therapy.

Intracerebral and subarachnoid bleedings/ Cerebral haemorrhage and SAH
Date: Friday 16 May 2008  
Time: 9:50 - 10:00 -  Room: Clio/Thalie
Chair: A. Demchuk, Canada and C. Stapf, France

12
Intra-cerebral haemorrhages: is there any differences in baseline characteristics and short-term outcomes between hospital- and population- based registries?
C. Cordonnier    M.P.Rutgers    F. Dumont    M. Pasquini    J.P.Lejeune    Y. Béjot    X. Leclerc    M. Giroud    D. Leys    H. Hénon
 

Lille University Hospital

FRANCE

We need a better understanding of the natural history of intra-cerebral haemorrhages (ICH), with cohorts representing the whole spectrum of the disease. Our aim was to identify potential differences in baseline characteristics and short-term outcomes of patients with non-traumatic ICH, included in a hospital- and in a population-based stroke registry. Method We compared 373 patients recruited in a University Hospital and the last 373 ICH patients included in a population-based registry. Both cohorts included consecutive patients with non traumatic parenchymal haemorrhages. In the hospital cohort, we collected data from all patients admitted in the emergency room, irrespective of the clinical severity and of the specialist in charge of the patient. Results In the hospital cohort, patients were younger and more often alcoholic, but these differences may be explained by the younger age and a higher prevalence of alcoholism in this area. Patients had also more frequently hypercholesterolemia, and were more often under antiplatelet therapy. Both cohorts did not differ for intra-hospital case-fatality rate. Discussion The characteristics of patients included in the hospital cohort were very close to those of patients from a population-based registry, and the differences observed are likely to be explained by differences in the characteristics of the populations in the two areas and different periods of recruitment. Recruiting patients in emergency rooms, and not in stroke units, neurological, or neurosurgical departments, has enabled us to build a cohort of ICH patients representative of the whole spectrum of the disease, with minimised recruitment bias and maximised precision of the variables collected. This cohort may, therefore, provide reliable information on the natural history of ICH.