XVII. European Stroke Conference
Nice, France

Oral Session:

Acute stroke: treatment concepts III
Date: Thursday 15 May 2008  
Time: 16:30 - 16:40 -  Room: Clio/Thalie
Chair: N. Bornstein, Israel and H. Mattle, Switzerland

01
BP lowering in Acute Stroke - the CHHIPS Pilot Study
A.K.Mistri    T.G.Robinson    J.F.Potter                                                 
CHHIPS and COSSACS Trial Groups

University of Leicester/University of East Anglia

UNITED KINGDOM

Introduction Elevated blood pressure (BP) levels immediately post-stroke are associated with an adverse prognosis in terms of death and dependency. However the benefit of lowering these elevated levels is still unclear. The CHHIPS trial tested the BP lowering efficacy of lisinopril and labetalol in acute stroke patients. Methods This multi-centre, prospective, randomised, double-blind, placebo-controlled, titrated-dose trial, recruited hypertensive cerebral infarct and haemorrhage patients (systolic BP>160mmHg) within 36 hours of symptom onset. Target systolic BP was 145-155mmHg or a 15mmHg SBP reduction within the first 24 hours achieved by up-titration of labetalol (lab) or lisinopril (lis) or placebo (plac), established treatment being continued for 2 weeks. Results 179 patients were recruited with a baseline BP 182(+/-17)/95(+/-13mmHg. BP fell from randomisation to 24 hours in all groups (mean (SE): lab 18(3); lis 25(3); plac 11(3) mmHg) and remained lower than baseline at 2 weeks (lab 11(2); lis 15(2); plac 9(2) mmHg). Over the initial 24 hours, SBP reduction was significantly greater in the lisinopril group (p=0.001) and the combined active treatment group (p=0.004), but not in the labetalol group (p=0.096), compared to placebo (lab 31(3); lis 32(3); combined lab/lis 31(2); plac 24(3) mmHg). At 2 weeks, SBP reduction was significantly greater in the combined active treatment group compared to placebo (31 (2) vs 24 (3) mmHg, p=0.045), with no significant difference in SBP or DBP reduction at 2 weeks for either treatment agent compared to placebo. There were no significantly greater adverse events with active treatment. Conclusions Lisinopril produces sustained SBP reduction at 24 hours. The hypotensive effects of labetalol are short-lived and frequent dosing/infusion may be required to produce sustained BP reduction. Further dose escalations are likely to be required for sustained BP reduction beyond 24 hours.

Acute stroke: treatment concepts III
Date: Thursday 15 May 2008  
Time: 16:40 - 16:50 -  Room: Clio/Thalie
Chair: N. Bornstein, Israel and H. Mattle, Switzerland

02
Lowering Blood Pressure in Dysphagic Acute Stroke Patients - CHHIPS Pilot Study
A.K.Mistri    T.G.Robinson    J.F.Potter                                                 
CHHIPS Trial Group

University of Leicester

UNITED KINGDOM

Introduction: Although elevated systolic blood pressure (SBP) levels immediately post-stroke are associated with an adverse prognosis in terms of death and dependency, the benefits of reducing these raised levels is still unclear. To date dysphagic stroke patients have in general been excluded from BP lowering trials. The CHHIPS trial tested the BP lowering efficacy of sublingual lisinopril and intravenous labetalol in acute stroke patients with dysphagia. Methods: This multi-centre, prospective, randomised, double-blind, placebo-controlled, titrated-dose trial, recruited hypertensive (SBP>160mmHg) cerebral infarct and haemorrhage patients within 36 hours of symptom onset. Target SBP was 145-155mmHg or a 15mmHg SBP reduction within the first 24 hours achieved by up-titration of intravenous labetalol, sublingual lisinopril or placebo. Results: 83 patients with dysphagia were recruited over 36 months. Repeated measures analysis for SBP for the three treatment arms at 4, 8 and 24 hours showed an overall significant difference between treatments with time (p<0.0001). There was a borderline significant reduction in SBP in the lisinopril dysphagic group compared to placebo at 8 hours (mean reduction 10 mmHg, -1 to 21, p = 0.07) and a significant reduction at 24 hours (mean reduction 12 mmHg, 2 to 23, p = 0.024), but not at 4 hours. In contrast, the labetalol dysphagic group had a significant reduction in SBP compared to placebo at 4 hours (mean reduction 16 mmHg, 95% CI 26 to 5, p = 0.005), but not at 8 and 24 hours. No increase in serious adverse events was seen with active treatment. Conclusions: Sublingual lisinopril is an effective antihypertensive agent in early acute stroke, with a sustained BP lowering effect at 24 hours. Intravenous labetalol is efficacious over the short-term (4 hours), and repeated dosing/infusion may be required to produce sustained BP reduction. We have demonstrated BP lowering efficacy of lisinopril administered via a novel (sublingual) route. Both active treatments appear to have an acceptable safety profile.

Acute stroke: treatment concepts III
Date: Thursday 15 May 2008  
Time: 16:50 - 17:00 -  Room: Clio/Thalie
Chair: N. Bornstein, Israel and H. Mattle, Switzerland

03
Candesartan gradually lowers BP following acute ischaemic stroke: The Acute Candesartan Cilexetil Outcomes Stroke Trial (ACCOST).
R.E.O'Brien    L. Palmer    D. Johnston    A.J.Hildreth    J.E.O'Connell    C.S.Gray                            
 

University of Newcastle upon Tyne

UNITED KINGDOM

Background and Aims Hypertension is an important modifiable risk factor for first ever and recurrent stroke. Evidence exists to support the active lowering of BP from several weeks after stroke, even from ‘normal’ levels. Early introduction of the angiotensin receptor blocker Candesartan in acute stroke patients with severe hypertension reduces vascular events without lowering blood pressure. ACCOST examined the safety of Candesartan given within 72 hours of stroke in normotensive and mildly hypertensive patients. Methods Two-phase randomised placebo controlled trial. Phase 1: Four-week double blind comparison of candesartan 4mg versus placebo, increased to 8mg if titration criteria were met, without target BP. Phase 2: Eight-week open-label study of candesartan versus an angiotensin converting enzyme-inhibitor (perindopril) based regime. Eligible patients were within 72 hours of acute ischaemic stroke, with BP > 120/70. Results Thirty-eight patients were included in the study, 19 in each group. Mean BP pre-treatment was 147/84mmHg in the candesartan group and 148/90mmHg in the placebo group. Results of phase 2 are reported here. After 12 weeks, mean (95% CI) systolic BP changes were -10.0 (-21.2 to 2.7) mmHg for candesartan and -1.6 (-10.5 to 7.3) mmHg for placebo/perindopril (p=0.223). Mean (95% CI) diastolic BP changes were -3.7 (-10.2 to 2.7) mmHg for candesartan and -1.9 (-9.3 to 5.5) mmHg for placebo (p=0.699). Precipitous falls in BP were not observed. More patients in the candesartan treated group were at target BP by 12 weeks (42% vs. 26%). Conclusions Mean BP changes over 12 weeks were not significantly different between the groups although a trend towards greater BP reduction was observed with candesartan. Early introduction of candesartan appears to be safe and is more likely to lead to early achievement of target BP. Further work is required to investigate whether early use of candesartan influences outcome after acute ischaemic stroke.

Acute stroke: treatment concepts III
Date: Thursday 15 May 2008  
Time: 17:00 - 17:10 -  Room: Clio/Thalie
Chair: N. Bornstein, Israel and H. Mattle, Switzerland

04
Feasibility and time efficiency of MRI before Thrombolytic Treatment of Acute Stroke in the 3 Hour Time Window.
C. Sølling    M. Ashkanian    N. Hjort    G. Andersen    L. Østergaard                                   
 

Center of Functionally Integrative Neuroscience

DENMARK

Background Magnetic resonance imaging (MRI) in acute stroke patients provides important diagnostic information and may facilitate individualized treatment, yet longer scan times could delay treatment. This study estimates feasibility of MRI, and analyzes time data in an acute stroke referral center. Materials and Methods MRI was first choice imaging modality as part of a project in normal working hours. We prospectively recorded consecutive patients referred as candidates for thrombolytic treatment in a two year time period. Contraindications to MRI and reasons for not performing MRI were noted. Time of onset of symptoms, arrival at the hospital, imaging time and time to treatment were carefully recorded and important time intervals were calculated. Results We received 174 patients of which 161 required acute imaging. MRI was performed in 141, yielding a feasibility rate of 88 %. With an experimental MRI protocol, median “door-to-needle time” (DNT) in MR scanned patients (70 minutes), did not differ from DNT of patients treated after conventional CT during the same time period at our institution outside the project (N=17, DNT=66 minutes, p=0.27) or the SITS-MOST registry (DNT=68 minutes). Conclusions MRI can be performed in the majority of acute stroke patients without delaying treatment.

Acute stroke: treatment concepts III
Date: Thursday 15 May 2008  
Time: 17:10 - 17:20 -  Room: Clio/Thalie
Chair: N. Bornstein, Israel and H. Mattle, Switzerland

05
STATIN TREATMENT PRIOR TO CAROTID ENDARTERECTOMY (CEA) REDUCES INFLAMMATION AS SEEN ON CONSECUTIVE 18FDG-PET IMAGING
M.A.Font Padros    A. Fernandez    I. Rico    M.M.Turu    A. Luque    C. Gamez    M. Slevin    F. Rubio    L. Badimon    J. Krupinski
 

Hospital Universitari de Bellvitge

SPAIN

Background Vulnerable atherosclerotic plaques have been characterized by their expression of high numbers of inflammatory cells. Fluorine-18 fluorodeoxyglucose (18-FDG) accumulates in inflamed tissues and several groups have established that inflamed blood vessels and atherosclerotic lesions have increased uptake of 18-FDG. Our aim was to investigate the effect of statin treatment prior to CEA on 18-FDG carotid uptake on consecutive PET scans in the contralateral carotid artery with low to moderate stenosis. Methods We enrolled 14 patients with unilateral carotid artery stenosis scheduled for CEA. In group A (n=7) patients received statins for at least 4 weeks prior to the first PET and continued throughout the study. In a group B (n=7) patients did not receive treatment with statins. The follow-up 18-FDG-PET was performed 116 +/- 22 days after CEA. A semiquantitative analysis of FDG-uptake values based on maximum standardized uptake value. Slice-activity curves were calculated in order to visualize plaque and basal metabolism. Carotid plaque morphology was assessed by examination of haematoxylin and eosin stained sections and the peroxidase method was used for immunohistochemical staining with monoclonal anti-CD68 antibody. Computer–assisted planimetry was used to quantify areas of staining in order to validate the PET FDG uptake correspondence with macrophage infiltrates. Results Statin treatment prior to the CEA (group A vs. B) was associated with a more pronounced decrease in 18-FDG-uptake on second PET in the contralateral carotid artery (p<0.05). This effect was independent of levels of total-cholesterol, LDL-cholesterol, HDL-cholesterol or triglycerides between two studied groups. We found a statistically significant correlation between the degree of FDG accumulation and the presence of macrophages in the atherosclerotic plaques (R=0,8, p<0,005). Discussion This pilot study demonstrates that pleiotrophic effects of statins in reduction of inflammation can be visualized in vivo by 18-FDG-PET imaging.

Acute stroke: treatment concepts III
Date: Thursday 15 May 2008  
Time: 17:20 - 17:30 -  Room: Clio/Thalie
Chair: N. Bornstein, Israel and H. Mattle, Switzerland

06
Systematic review of blood biomarkers to aid diagnosis in acute ischaemic stroke
W.N.Whiteley    M.C.Tseng    P. Sandercock                                                 
 

University of Edinburgh

UNITED KINGDOM

INTRODUCTION Blood markers could help improve the diagnosis of stroke in the acute setting, especially if imaging is normal or not immediately available. We planned systematically to review the diagnostic performance of blood biomarkers. METHODS: We searched Medline and EMBASE from 1966 to 1st December 2007, reference lists and personal files. Two authors reviewed the papers and performed data extraction. RESULTS: We identified 3101 studies of which 21 were eligible. Diagnostic test performance was formally examined in only 4/21 studies. Sensitivity and sensitivity, applying a prespecified diagnostic threshold for a positive test, was examined in 6/21 studies. The remaining 15 studies that employed a data-dependent (post hoc) threshold, 0/15 validated the test in a new cohort. 4/21 studies measured the biomarker blinded to clinical status. The 21 studies tested 58 single biomarkers and 7 panels (made up of several markers) in 2928 stroke patients and 1569 controls. Sensitivity was >90% for: nucleoside diphosphokinase A (NDKA), RNA binding protein, UFD-1, NMDA receptor 2 fragment, NMDA receptor antibodies. Specificity was over 90% for: RNA-binding protein , ubiquitin fusion degradation protein -1, NDKA, glutathiosone-s-transferase P, ischaemia modified albumin, visin like protein, beta globin DANN, NR2 fragments, S100 beta, fatty acid binding protein, neurone specific enololase, NR2A/2B Ab, myelin basic protein and thrombomodulin. Choice of control subject had a substantial effect on test specificity, CONCLUSIONS: Several blood markers performed well but need to be validated in new cohorts of patients with suspected stroke, with blinding and comparison with appropriate controls. None can yet be recommended for use in routine clinical practice.

Acute stroke: treatment concepts III
Date: Thursday 15 May 2008  
Time: 17:30 - 17:40 -  Room: Clio/Thalie
Chair: N. Bornstein, Israel and H. Mattle, Switzerland

07
HYPERGLYCEMIA AND RESISTANCE TO EARLY AND LATE MIDDLE CEREBRAL ARTERY RECANALIZATION AFTER THROMBOLYSIS IN ACUTE STROKE
M. Millán    J.F.Arenillas    M. Rodríguez-Yáñez    N. Pérez de la Ossa    P. Sandoval    Y. Silva    L. Dorado    C. Guerrero    A. Dávalos       
 

Hospital Universitari Germans Trias i Pujol

SPAIN

Background: Hyperglycemia (HG) has been associated with an antifibrinolytic effect and resistance to early (within 2 hours) arterial recanalization after thrombolysis. We aimed to study the effect of HG on early and late recanalization of middle cerebral artery (MCA) occlusion in patients treated with tissue plasminogen activator (tPA) Methods: We prospectively studied 85 ischemic stroke patients (median age 68, NIHSS 14) treated with IV tPA within 3 hours from symptoms onset who showed MCA occlusion on prebolus transcranial Duplex (TCDx) examination. TCDx follow-up was performed at 2, 6, 12 and 24 hours after tPA. Thrombolysis in Brain Ischemia (TIBI) grades were used to define complete, partial or absent MCA recanalization. Baseline serum glucose and plasma glycosylated hemoglobin (HbA1c%) levels were recorded. HG was defined as serum glucose > 150 mg/dL Results: Complete or partial MCA recanalization was achieved in 50.6% of patients at 2 hours, 60.8% at 6 hours, 72.7% at 12 hours and 84.7% at 24 hours. HG at baseline was found in 20 (23.5%) patients. HG was associated with lower recanalization rates at 2 (11.9% vs 36.6%, p=0.009) and 6 (14.6% vs 35.5%, p=0.031) hours, but no differences were found at 12 and 24 hours. No other baseline variables, including HbA1c, were associated with early or late resistance to MCA recanalization. Acute HG remained as an independent predictor of no recanalization at 2 hours (OR, 4.89; 95%CI 1.4-15.9, p=0.009) and 6 hours (OR, 3.45; 95%CI 1.1-10.7, p=0.032) after adjustment for age, stroke severity and proximal MCA occlusion. No significant effect was observed beyond 6 hours Conclusion: These findings confirm that HG is associated with resistance to MCA recanalization up to 6 hours after thrombolysis in ischemic stroke patients

Acute stroke: treatment concepts III
Date: Thursday 15 May 2008  
Time: 17:40 - 17:50 -  Room: Clio/Thalie
Chair: N. Bornstein, Israel and H. Mattle, Switzerland

08
Intraarterial Treatment for Acute Anterior Circulation Ischemic Strokes due to Intracranial Large Vessel Occlusion beyond 8 Hours - Preliminary Result
S. Zaidi    R. Lin    N. Vora    R. Gupta    V. Reddy    M. Hammer    K. Uchino    L. Wechsler    A. Aleu    T. Jovin
 

University of Pittsburgh Stroke Institute

USA

BACKGROUND: Selection of patients with acute ischemic stroke (AIS) for endovascular therapy is currently based on strict time window. We sought to determine the treatment effects of endovascular therapy on AIS patients presenting beyond 8 hours of symptom onset, when selection is based on pathophysiological characteristics assessed through neuroimaging. METHODS: We retrospectively identified AIS patients with carotid terminus, middle cerebral artery M1 and/or M2 division occlusion treated with endovascular modalities from 01/2003 to 12/2007 at our center. We classified patients into 0-8hr vs >8hr groups, based on time from symptom onset to first diagnostic angiographic run. All patients treated beyond 8hrs had large mismatch on imaging (MR or CT perfusion) prior to intervention. Patient demographics (age, sex), risk factors, thrombus site, baseline National Institute of Health Stroke Scale (NIHSS) score, and treatment modality (IA tPA, angioplasty, stent, and/or MERCI embolectomy device) were compared between the groups. Endpoints are outlined in the table. RESULTS: Of 160 consecutive patients, 37(23.1%) were treated after 8hrs. Patients in 0-8hr treatment group had a higher mean baseline NIHSS score (18 vs 12, p<0.05); more patients in the >8hr group were treated with MERCI device (57 vs 41%, p0.05) and stenting (51.4 vs 29.3%, p0.003). No significant differences were found with respect to endpoints between the two groups, although a trend towards lower incidence of parenchymal hematoma (PH) and lower final diffusion weighted image (DWI) infarct volumes were detected in the >8hr group(see table). DISCUSSION: Imaging may identify AIS patients beyond 8hrs from symptom onset who can achieve good outcomes with endovascular treatment. Furture prospective trials are needed.

 
http://www.eurostroke.org/ni_graphics/t_aid3036.htm

Acute stroke: treatment concepts III
Date: Thursday 15 May 2008  
Time: 17:50 - 18:00 -  Room: Clio/Thalie
Chair: N. Bornstein, Israel and H. Mattle, Switzerland

09
Intra-arterial administration of microbubbles and continuous 2-MHz ultrasound insonation to enhance intraarterial thrombolysis
M. Ribo    C.A.Molina    B. Alvarez    M. Rubiera    J. Alvarez-Sabin    M. Matas                            
 

Unitat Neurovascular. Hosptial Vall d'Hebron

SPAIN

Microbubbles (MB) and ultrasound have shown to enhance thrombolytic effect of iv-tPA. We sought to evaluate the safety and efficacy of local MB administration during intra-arterial thrombolysis(IA) and continuous transcranial Doppler(TCD) monitoring on middle cerebral artery(MCA) recanalization METHODS. Patients with acute proximal MCA occlusion were treated with IA tPA (repeated 4mg up to 20mg or recanalization) and IA galactose based MB (up to 3 doses of 1 ml(400 mg/dl)). MBs and tPA were infused directly intra-clot through a microcatheter. TCD monitoring allowed continuous insonation at clot location. Retrieving devices were not used. Recanalization was angiographically assessed according to TICI reperfusion score and compared to simultaneous online TCD data. IA procedures were always stopped 6 hours after symptoms onset. Recanalization was reassessed with TCD at 12 hours after symptoms onset. Hemorrhagic transformation(HAT) was assessed at 24 hours. Neurological status was assessed with the NIHSS. At three months patients were considered independent if mRS was ≤2 RESULTS Of the 9 included patients, 7 received standard iv.tPA prior to IA rescue. Median pre-IA NIHSS was 20. Median time to IA initiation was: 175 minutes. Mean IA administered doses were: tPA 10mg, MB lml. TCD allowed direct visualization of massive MB arrival during every dose administration. After MB infusion, recanalization was confirmed in 7 patients (78%): complete-TICI3: 2 patients(22%), partial-TICI2: 5 patients(56%). A perfect correlation was observed between TICI and TCD scores. At 12 hours recanalization rate was still 78%, however complete recanalization increased to 56%. One patient(11%) experienced symptomatic HAT accounting for the only death. Median NIHSS evolution was: 12 at 24 hours and 10 at discharge. At 3 months 4 patients(44%) were independent CONCLUSION Ultrasound-activated intraclot-delivered MB and tPA may be a safe strategy to enhance the thrombolytic effect and increase recanalization rates Ongoing study: presented data will include all future treated patients