Abstracts

Abstract ID: A0004

MULTIDISCIPLINARY THROMBOLYTIC THERAPY FOR ACUTE ISCHEMIC STROKE IN A COMMUNITY-BASED HOSPITAL OF KOREA

H.J. Bae¹, M.K. Han¹, K.M. Chae¹, J.S. Koo¹, K.S. Hong², K.H. Yu³, B.C. Lee³

¹Departments of Neurology, Seoul National University Bundang Hospital, Eulji General Hospital, Eulji University School of Medicine, South Korea, ²Inje University Ilsan Paik Hospital, South Korea, ³Hallym University, South Korea

Background: To describe the performance and strategies of our multidisciplinary approach in thrombolysis and explore its efficacy and safety.

Methods: A consecutive series of 896 patients with acute ischemic stroke who were admitted within 7 days from the onset were recruited from January 1, 2004, to March 31, 2006. Intervals from onset to visit were classified as within 3, 3–6 and more than 6 h. The operation of thrombolysis and its methods were recorded. Clinical outcome was dichotomized as a modified Rankin scale (mRS) score of 0–1 vs. 2 or more at 90 days. Symptomatic intra-cerebral hemorrhage was defined as any hemorrhagic transformation with clinical deterioration within 36 h.

Results: A total of 72 (8.1%) patients (age = 66.3±13.2 years, initial mean NIHSS = 13.5±6.4), underwent thrombolysis, 34 (47.2%) with IV thrombolysis, 17 (23.6%) with IA thrombolysis, and 21 (29.2%) with both. Among 172 patients, who visited within 3 h, 59 (34.3%) received thrombolysis. Among 85, who visited 3–6 h, 11 (12.9%) had thrombolysis. After 6 h, 2 of 631 (0.3%) received thrombolysis. Clinical outcome at 3 months was available in 69 patients. Favorable outcome was observed in 39% (27/69), 48.5% (16/33) in IV group, 18.8% (3/16) in IA group, & 40% (8/20) in IV+IA. Hemorrhagic transformation occurred in 21% (15/72) and symptomatic hemorrhage was 8.3% (6/72, 2.9% in IV group; 11.8% in IA; 14.3% in IV+IA).

Conclusion: This study suggests that the efficacy and safety of our multidisciplinary approach may be acceptable.

Abstract ID: A0006

IV TPA FOR CEREBRAL ISCHEMIA: COMPARISON OF BASELINE CHARACTERISTICS AND OUTCOMES BETWEEN PATIENTS TREATED AT WORKING TIME AND AT NON-WORKING TIME

D. Leys, C. Lefebvre, C. Lucas, S. Debette, H. Henon

Department of Neurology, University Hospital of Lille, France

Background: At non-working time physicians are more tired, sometimes less experienced, and less easily share decisions with colleagues than at working time. This may influence selection of ischemic stroke patients for thrombolysis and outcomes. Our aim was to compare baseline characteristics and outcomes in patients treated with IV tPA at working and non-working times.

Methods: We compared demographic characteristics, vascular risk factors, previous vascular events, clinical–, imaging– and biological features at admission, delays before treatment, protocol violations and outcome at hour-24 and month-3, between patients treated at working (8:30 am–6:30 pm), and non-working (6:30 pm–8:30 am, Saturday, Sunday and non-working days) times. All patients were treated by a senior neurologist (a stroke specialist for 100% at working time and 25% at non-working time).

Results: We included 63 consecutive patients (31 at working time). Baseline characteristics did not differ during non-working time, but door-to-imaging time was shorter (20 vs. 30 min; p = 0.041) and protocol violations more frequent (p = 0.047). There was no difference in the proportion of patients with a modified Rankin scale ≤ 2 and mortality at third month.

Conclusion: This study showed no significant difference of baseline characteristics and outcomes between patients treated at working and non-working times. A larger study should test whether the higher rate of protocol violations influences outcome, which was not the case here.

Abstract ID: A0028

A SYSTEMATIC ANALYSIS OF FACTORS PREDICTING OUTCOME IN INTRA-ARTERIAL (IA) THERAPY OF ACUTE ISCHEMIC STROKE

P. Mandava, T.A. Kent

Michael E DeBakey VA Medical Center Stroke Program, Baylor College of Medicine, USA

Background: We performed a systematic review of outcomes in case series of intra-arterial therapy for acute stroke. Since baseline NIHSS and age predict > 90% of the outcome variance, we compared these studies to natural history models based on these factors. We identified factors that differentiated the worst and best performers relative to predicted outcomes.

Methods: A literature search identified IA studies with > 10 subjects, baseline NIHSS and age, and 3 month outcomes. Outcomes were compared to Uchino et al. (2001) predictive model. Relative differences from prediction were ranked from best to worst, divided into quartiles and the best and worst quartiles compared for pre-identified characteristics.

Results Twenty-nine different series fit the criteria representing 1094 patients. Relative to predicted outcomes, reduction in mortality was 2±46%. The seven best performers would have prevented 42 out of 205 patient deaths while the seven worst performers would have resulted in an excess of 29 out of 181 patient deaths. Better outcomes relative to prediction was associated with a more severe baseline NIHSS (21.1±4.08 vs. 16.3±3.14; p = 0.028) and lower dose of urokinase (p = 0.0034) (the most common agent employed). Neither use of other agents, year of publication or mechanical disruption was related to outcome.

Conclusion: Our analysis indicates that IA therapy is more appropriate for patients with severe strokes and that higher doses of urokinase are associated with greater mortality.

Abstract ID: A0030

FACTORS INFLUENCING THE ACUTE STROKE THROMBOLYSIS IN HYDERABAD, A METROPOLITAN CITY OF SOUTH INDIA

S. Kaul, R. Borgohain, A.K. Meena, S. Sitajaylakshmi, A. Suvarna

Nizam's Institute of Medical Sciences, Hyderabad, India

Background: Use of thrombolytic therapy for ischemic stroke in India is limited. We report our experience of recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke at a University hospital in Hyderabad, a metropolitan city of south India.

Methods: Data of patients of acute stroke treated reporting to hospital within 3 h, between September 2000 and May 2005 was analyzed. The reason for not getting the thrombolytic treatment and the outcome of those having received the intra-venous thrombolytic treatment was studied.

Results: Out of 2740 patients of stroke admitted in the Nizam Institute of Medical Sciences, a University hospital of South India, only 85 patients (3%) reached hospital within 3 h of onset, of whom, 45 patients received rt-PA. The causes of non-administration were intra-cerebral hemorrhage (15), non-affordability (15), uncontrolled hypertension (2) and reluctance to accept the risk of complications (8). Out of the 45 thrombolysed patients, 21 (47%) had full recovery, 11 (24%) had minimal neurological deficits, 4 (9%) were dependent and 2 patients (4.4%) had a fatal brain hemorrhage.

Conclusion: Very few stroke patients reach hospital within the window period. Among these about a half do not get treatment due to high cost and fear of complications. The outcome in thrombolysed patients are comparable to those reported in NINDS study.

Abstract ID: A0042

THE IMS III TRIAL: A COMBINED INTRAVENOUS AND INTRA-ARTERIAL APPROACH TO RECANALIZATION

M.D. Hill¹, J.P. Brodick², T. Tomsick², P. Khatri², A. IMS3 Trialists²

¹University of Calgary, Canada, ²University of Cincinnati, USA

Background: To examine the efficacy and safety of a combined intravenous (IV) and intra-arterial (IA) approach to re-canalization as compared to standard intravenous rt-PA in patients with ischemic stroke.

Methods: The IMS III Trial is an NIH-funded, Phase III, randomized, 41+ –center open-label, 900 subject clinical trial examining whether a combined IV/IA approach to re-canalization is superior to standard IV rt-PA alone when initiated within 3 h of large acute ischemic stroke (NIHSS ≥ 10, ages 18–80). The primary outcome measure is mRS of 0–2 at 3 months. Subjects will be randomized in a 2 : 1 ratio with more subjects assigned to the combined IV/IA group. The IV-only group will receive standard IV rt-PA at 0.9 mg/kg (with 10% bolus) over one hour and no further therapy will be administered acutely. The IV/IA group will receive 0.6 mg/kg over 40 min (with 10% of 0.9 mg/kg dosing bolus) followed immediately by angiography. If an appropriate vascular lesion is identified in the combined group at angiography, treatment will continue with either the Concentric clot removal device, infusion of rt-PA (up to 22 mg) via the EKOS MicroLysUS microcatheter delivering low-energy ultrasound, or infusion of rt-PA (up to 22 mg) via a standard microcatheter.

Results: Sites in North America have been recruited and the study is actively recruiting patients.

Conclusion: A randomized comparison of standard intravenous rt-PA with a combined approach is critical to determine the future direction of acute stroke therapy.

Abstract ID: A0064

USE OF IV TPA FOR TREATMENT OF ACUTE ISCHAEMIC STROKE IN A REGIONAL GENERAL HOSPITAL

S.F.K. Hon, T.H. Tsoi, C.M. Cheung, M. AuYeung, C.N. Lee

Pamela Youde Nethersole Eastern Hospital, Hong Kong

Background: There is no consensus about the use of IV TPA for acute ischaemic stroke in Hong Kong.

Methods: Retrospective review of the use of IV TPA treatment from the data of our stroke database.

Results: A total of 20 patients were given IV TPA for acute ischaemic stroke from January 2003 to September 2006: three in year 2003 (0.4% of all ischaemic stroke admission), 6 (0.9%) in 2004 and 5 (1%) in 2005, and six in 2006 (up to September). Three patients developed stroke during hospitalization for other causes. The age ranged from 42 to 81, with two patients aged less 60 (both 42). The mean NIHSS score on admission was 18, ranged 6–36. Two patients woke up with the neurological deficit and one patient presented beyond 3 h (210 min). There was no haemorrhagic transformation complication in these three patients. For those TPA given within 3 h from stroke onset, the mean needle-to-onset time is 143.2 min, ranged 105–180 min.12 patients showed improvement of more than or equal to two points in NIHSS after iv TPA treatment, amongst these six patient showed dramatic improvement (> 6 points in NIHSS). One patient developed symptomatic (HT) (onset-to-needle time was 170 mins). There was no deterioration or improvement in the NIHSS score. There was 2 mortality. Both patients were older than 70 years, with total MCA syndrome and a high NIHSS (> 25), TPA were given within 3 h time window. Both of them died of complication of malignant MCA syndrome.

Conclusion: Use of IV TPA for acute stroke was feasible and safe in a regional general hospital.

Abstract ID: A0003

A PILOT STUDY OF EXTERNAL COUNTERPULSATION (ECP) FOR ISCHEMIC STROKE PATIENTS WITH LARGE ARTERY OCCLUSIVE DISEASE

J.H. Han, W.H. Leung, W.M. Lam, O.Y. Soo, K.S. Wong

The Chinese University of Hong Kong, China

Background: ECP is a non-invasive treatment that increases perfusion to internal organs. It is an established treatment for ischemic heart disease but the experience for cerebral ischemia is unknown. We aimed to explore its effect on cerebral blood flow (CBF), neurological and functional recovery after stroke.

Methods: We did a randomized, crossover, assessment-blinded trial in patients with recent ischemic stroke. Patients were randomized to either early (ECP week 1–7 and no ECP week 8–14) or late group (no ECP week 1–7 and ECP week 8–14). ECP treatment consisted of 35 daily one-hour sessions. Primary outcomes were change in NIHSS and CBF (estimated by color velocity imaging quantification, CVIQ). Secondary outcomes were change in NIHSS, CVIQ, and percentage of patient with excellent functional recovery (mRS ≤ 2, BI > 90) at end of week 7 and 14.

Results: A total of 50 patients were recruited. At baseline, mean NIHSS for early and late groups were 5.4 vs. 4.2, and for CVIQ 675.2 vs. 652.0 ml/min, respectively. Intention-to-treat found a change of 2.1(95% CI, 1.5–2.7) on NIHSS vs. 1.3 (0.6–1.9) or ECP (p = 0.06), and for CVIQ 27.3 vs. 21.0 (p = 0.81) after adjusting for treatment sequence. At end of week 7, there was a significant change in NIHSS (E 3.5±3.4 vs. L 1.9±2.3; p = 0.04) and a trend toward better brain perfusion. There were no differences for both outcomes at end of wk 14. A favorable functional outcome was found at end of week 14 (E 100% vs. L 76%; p = 0.02).

Conclusion: Early ECP appears to enhance neurological recovery and brain perfusion in stroke patients.

Abstract ID: A0008

INTRACEREBRAL HEMORRHAGES IN KOREAN PATIENTS WITH CEREBRAL AUTOSOMAL DOMINANT ARTERIOPATHY WITH SUBCORTICAL INFARCTS AND LEUKOENCEPHALOPATHY

J-C. Choi, S.Y. Kang, J.H. Kang, J.K. Park

Cheju National University Hospital, South Korea

Background: Intracerebral hemorrhage (ICH) has been described only sporadically for patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, cerebral microbleeds (CMBs) were found in 31–69% of the patients with CADASIL and this predicted an increased risk of ICH. The purpose of this study was to investigate the frequency of ICHs in our CADASIL patients and to analyze the relationship between the presence of ICH and other clinical or neuroradiological features.

Methods: We studied 27 consecutive symptomatic patients with CADASIL from 24 families between January 2000 and May 2006. The vascular risk factors were recorded, including hypertension, diabetes mellitus, smoking, heavy drinking, and hyper-cholesterolemia. We reviewed all the CT and MR images and evaluated the number, location of the ICHs, white matter hyperintensities, and CMBs.

Results: Twelve ICHs were found in eight patients (29.6%) and ICH was the initial neurological manifestation for four patients. The number of CMBs was higher in patients with ICH (27.75±26.77 vs. 9.93±19.56, p = 0.006). The patients with ICH had significantly worse neurological outcomes than the patients without ICH.

Conclusion: We found that as many as 29.6% of the symptomatic patients with CADASIL had ICHs. Their presence was closely related with the number of CMBs and was associated with worse neurological outcome status.

Abstract ID: A0015

TRIAL DESIGN OF CILOSTAZOL IN ACUTE ISCHEMIC STROKE TREATMENT (CAIST) STUDY

Y.S. Lee¹, S.H. Lee², J.S. Koo³, K.S. Hong⁴, Y.J. Cho⁴, J.M. Park

¹Seoul National University Boramae Hospital, South Korea, ²Seoul National University Hospital, South Korea, ³Eulji University School of Medicine, South Korea, ⁴Ilsan Paik Hospital, Neurology, Clinical Research Center, South Korea

Background: Currently, aspirin is the only proven effective antiplatelet agent in acute ischemic stroke. However, the net benefit is small and the bleeding or gastrointestinal distresses are major limitations. Cilostazol, a phosphodiesterase III inhibitor, has been known to prevent recurrent stroke and progression of intracranial stenosis.

Methods: CAIST trial is a double blind, randomized, multi-center, aspirin controlled trial. Patients with acute ischemic stroke within 48 h from onset are included. Major exclusion criteria are as following: baseline NIHSS > 15 points; previous use of anti-platelets or anticoagulants; congestive heart failure or potential cardiac source of embolism; severe hyper– or hypotension; anemia or thrombocytopenia; abnormal liver or renal function. Cilostazol 200 mg/day or aspirin 300 mg/day is given for 90 days. As a primary outcome, the frequency of modified Rankin scale 0, 1, 2 at 90 day will be compared. Secondary outcomes are composed of progression of neurological deficit within 7 days or predefined favorable outcomes of stroke scales at 90 day. Bleeding complications or cardiovascular events (stroke, MI, vascular death or re-hospitalization) within 90 days are evaluated. As a non-inferiority trial, the sample size was calculated as 199 subjects in each group, and the statistical analysis will be done by intention-to-treat base.

Results: The study has been started from January 2006, and the last follow-up is expected in September 2007.

Conclusion: ClinicalTrials.gov NCT00272454.

Abstract ID: A0041

A ROBUST PROGNOSTIC ADVANTAGE WITH “LATE” RISING BODY TEMPERATURE PROFILES IN THE ECASS-I DATA BASE

J. Mau, S.D. Jayavel, M. Yong

Sarala Devi Jayavel, Germany

Background: Recent analysis of body temperature (BTp) profiles in a smaller data set suggested that the dynamics of BTp might independently contribute to long-term prognosis. This was to be reexamined in a larger subset of ECASS-1.

Methods: A total of 615 patients had received trial medication within 6 h from symptom onset, randomly assigned to either 1.1 mg/kg rt-PA or placebo. BTp was measured at baseline, after 2 and 24 h in 461 patients. Including profiles of only 2 readings, a total of 574 patients became available, instead. End points were long-term complete dependency or death (mRS 5 or 6) and mortality within 90 days. Profiles of individual BTp readings were grouped as constant, either only early or only late rising, persistently rising, dropping in any way, concave, or convex. Stepwise logistic regression comprised all baseline characteristics from the database.

Results: Baseline characteristics such as CT scan findings of infarct signs (p = 0.0062) and of hypo-density extension (p = 0.01), BTp (P < 0.0001) and been on aspirin (p = 0.04), showed significant associations with types of 24 h profiles of BTp. After adjustment for known confounders and the effect of rt-PA, the late increase in BTp contributed independently and as it significantly reduced the risk of poor outcome (OR = 0.464; 95% CI 0.250–0.862; p = 0.0150) and of mortality (OR = 0.477; 95% CI 0.244–0.933; p = 0.0305).

Conclusion: Late rising body temperature was confirmed to reduce the risk of very poor outcome. Hence, early-phase body temperature dynamics deserve further study.

Abstract ID: A0052

INTERACT (INTENSIVE BLOOD PRESSURE REDUCTION IN ACUTE CEREBRAL HAEMORRHAGE TRIAL): PROGRESS REPORT

Y. Huang, C.S. Anderson, L. Morgenstern, B. Neal, J. Chalmers

Peking University First Hospital, China

Background: Elevated blood pressure (BP) is common and is associated with poor outcomes in intra-cerebral haemorrhage (ICH), but the benefits of early BP lowering are uncertain. INTERACT (ACTRN012605000391673) is an open randomised trial comparing effects of a management policy of early intensive, titratable, BP lowering against guideline-based BP management in ICH.

Methods: Patients with ICH (within 6 h onset) and high systolic BP (150–220 mmHg), without indication/contraindication to BP lowering, are eligible. Active group patients have BP lowering to systolic BP goal (≤ 140 mmHg) within one-hour and maintained for 7 days (or death/discharge). Controls receive AHA guideline BP management.

Results: To date, 180 of 400 patients in the Vanguard phase with ICH volume indices as primary outcome have been enrolled from 40 sites, representing about one quarter of screened ICH patients. Main reasons for exclusion are outside time window (40%) and low GCS (15%) at presentation. Two thirds of patients have been randomized and commenced BP lowering within the 6 h from stroke onset time window. Achieved BP and group differences indicate early BP lowering is feasible and without treatment-related SAEs.

Conclusion: Early BP lowering is feasible in the context of a large-scale clinical trial to provide reliable evidence of effectiveness of this treatment strategy.

Abstract ID: A0001

UTILIZATION OF A MODIFIED WOLF MOTOR FUNCTION TEST TO EVALUATE THE PROGRESS OF UPPER LIMB FUNCTIONAL RECOVERY OF STROKE PATIENTS

G. Shum, T. Ho, R. Lam, E. Chan

Physiotherapy Department, United Christian Hospital, Hong Kong

Background: In Hong Kong, handgrip strength is the conventional physiotherapy outcome measure for the functional recovery of upper limb. The application of a comprehensive and reliable assessment tool for upper limb functional recovery of stroke patients could enhance clinical communications among health professionals. This study was to evaluate the application of Wolf Motor Function Test (WMFT) as an objective and quantitative assessment tool for the upper limb functional recovery in stroke patients.

Methods: A total of 32 stroke subjects (age: 65±10 years; onset: 75±60 days) had their initial assessment completed at the first physiotherapy attendance and after 2 months of physiotherapy treatment. Dependent samples paired t-test was used to examine the progress in grip strength, the mean WMFT functional ability score and the median time domain.

Results: Significant differences were found in the grip strength (mean difference: 3.0±3.7 kg; p = 0.001) and the mean WMFT score (mean difference: 0.6±1.0; p = 0.030). However, there were no significant differences in the median time domain (mean difference: 0.27±4.79 s; p = 0.756).

Conclusion: The six-point functional ability scale of WMFT helps to quantify both the proximal and distal joint control of the affected limb in stroke patients. The outcome measures are specific, functional and clinically meaningful to interpret the progression of the affected upper limb. Modified WMFT (without the time domain) is suggested to enhance the clinical interpretation of the upper limb functional recovery.

Abstract ID: A0002

EARLY ASSESSMENT OF NIHSS AFTER IV TPA IN CLINICAL PRACTICE

S. Debette, C. Lefebvre, M. Girot, H. Henon, D. Leys

Department of Neurology, University Hospital of Lille, France

Background: The time-course of neurological deficits during the 1st week after IV tPA for acute cerebral ischemia and its influence on the 3-month outcome is not well known.

Methods: We prospectively included 51 consecutive patients receiving a standard dose of IV tPA for acute middle cerebral artery infarction. We assessed the NIHSS score at 2 h, 24 h and on 7th day after IV tPA and evaluated if early recovery is a good predictor of functional outcome at 3rd month. Good functional outcome (FO) was defined as a modified Rankin scale ≤ 2 at 3rd month.

Results: Patients whose NIHSS score improved at hour-2 (n = 27) more frequently had a good FO compared to those with unchanged or worsened NIHSS (59.3% vs. 25.0%, p = 0.02). Among patients whose NIHSS improved at hour-2, those with a bad FO had a less dramatic drop in NIHSS at hour-2 than those with a good FO (p = 0.02). Among patients who have NIHSS did not improve at hour-2, those with a good FO started improving after 24 h. In a multivariate model, good FO was associated with a lower NIHSS score before IV tPA and with decreasing delta-NIHSS within the first 2 h while the association with the NIHSS change between 2–24 h and between 24 h–day 7 was not significant.

Conclusion: Improvement of the NIHSS scores 2 h after initiation of IV tPA was strongly associated with FO at third month. The NIHSS time-course suggests that the clinical effect of tPA takes place mainly within the 2 h following treatment initiation.

Abstract ID: A0017

RELIABILITY AND VARIABILITY OF DIFFUSION-WEIGHTED IMAGING IN DIAGNOSIS OF EXTENDED AND RECURRENT INFARCTS 7 DAYS AFTER ACUTE ISCHEMIC STROKE

Q. Hao¹, W.W.M. Lam², W.C.W. Chu², V.C.T. Mok¹, K.S. Wong¹

¹Department of Medicine & Therapeutics, Prince of Wales Hospital, Hong Kong, ²Department of Diagnostic Radiology and Organ Imaging, Prince of Wales Hospital, Hong Kong

Background: Diffusion-weighted imaging (DWI) is the most sensitive clinical test available in detection of acute and hyper-acute stroke. Furthermore, DWI was also considered as a surrogate marker of stroke outcome. However, the reliability and variability of DWI in identifying infarct extension and new recurrent infarcts are unknown.

Methods: A total of 51 patients who were admitted consecutively to an acute stroke unit (ASU) with ischemic stroke underwent DWI on first and seventh day of admission. Topography of the acute infarcts and the presence of infarct extension and/or recurrent infarcts were documented by two independent radiologists. Inter-rater agreement was calculated using the κ value.

Results: At the follow-up scan on day 7, inter-rater agreement was excellent for detection of both extended infarcts (κ = 0.92) and new recurrent infarcts (κ = 0.85).

Conclusion: DWI has excellent reliability and little variability in detecting extended infarcts and new recurrent infarcts after the first scan.

Abstract ID: A0018

BLOOD PRESSURE RESPONSE TO IV THROMBOLYSIS IS UNRELATED TO RECANALISATION

K.W. Muir, J.L. Riley

University of Glasgow, United Kingdom

Background: The relationship of blood pressure (BP) to stroke outcome is debated. Both high and low BP acutely appears related to poorer outcome. A recent report suggested that lower BP was related to successful re-canalisation with intra-arterial (i.a) thrombolysis.

Methods: Retrospective review of BP records for all patients receiving IV rt-PA from at a single institution. Systolic (SBP), diastolic (DBP) BP was derived from routine nursing records. Patients were classified as having re-canalised or not blind to BP data. Re-canalisation was defined by (1) partial or complete patency of previously occluded vessel on follow-up CTA, MRA, DSA at 24–72 h; (2) resolution of a previously hyper-dense artery sign on plain CT; (3) restoration of normal flow on TCD; or (4) clinical improvement by NIHSS >7 points or to 0 or 1 at 24 h. Repeated measures ANOVA of SBP and DBP using admission BP as a covariate was conducted.

Results: BP records were available for 76 of 138 treated patients, mean age 69 years, median NIHSS 14.5, and onset to treatment time 176 min 36 re-canalised. Re-canalisation was associated with favorable outcome (odds ratio for mRS 0–1 9.39, 95% CI 1.92–45.8, p = 0.006 by Cochran-Mantel-Haenszel). SBP was higher at all time points admission-24 h in non-re-canalisers. There was no effect of re-canalisation on SBP (p = 0.710) or DBP (p = 0.962).

Conclusion: Systolic BP was consistently higher in non-re-canalisers over 24 h after IV rt-PA but there was no difference in BP over time with re-canalisation status.

Abstract ID: A0034

WHY ARE WOMEN WITH STROKE LESS LIKELY TO RECEIVE TISSUE PLASMINOGEN ACTIVATOR OR BE ENROLLED IN A CLINICAL TRIAL?

G.J. Gubitz¹, J.M. Reid¹, D. Dai², C. Christian¹, S.J. Phillips¹

¹Queen Elizabeth II Health Sciences Center, Canada, ²Dalhousie University, Canada

Background: Studies suggest that women with ischemic stroke (IS) are investigated and treated less aggressively than men with lower unadjusted rates of tissue plasminogen activator (tPA) use. We tested whether gender differences in investigation and treatment of stroke are due to confounding factors.

Methods: Gender differences in rates of investigation, i.v. tPA use and stroke outcomes were tested using a hospital stroke registry database, adjusting for confounders with multivariate analysis.

Results: Of 2725 stroke patients admitted between May 1996 and February 2006, 88% had IS and 48% were women. Women were significantly (p < 0.001) older (median age 77 [IQR, 67–83] vs. 70 [61–78] years), with more severe strokes and lower pre-stroke independence rates (78 vs. 87%) than men. There was no gender difference in adjusted rates of investigation. tPA treatment rates for IS presenting < 3 h of onset were higher for men than women (24 vs. 14%, p = 0.0003), even accounting for baseline differences (OR 1.8, 95% CI [1.3–2.7], p = 0.002). The adjusted odds ratio for clinical trial enrollment comparing women to men was 0.61 (0.42–0.90, p < 0.01). There were no gender differences in age-adjusted rates of in-hospital mortality, being discharged home and length of hospital stay.

Conclusion: Gender differences after stroke were mostly explained by differences in baseline variables. However, women were less likely to be treated with tPA or be enrolled in a clinical trial. The reasons for this are unclear and require further study.

Abstract ID: A0040

REVIEW OF CHARACTERISTICS OF BLOOD PRESSURE PROFILES AND LONG-TERM OUTCOME IN THE ECASS-II DATA BASE

M. Yong, J. Mau

Institute of Statistics in Medicine, University Hospital Duesseldorf, Germany

Background: Certain characteristics of early blood pressure (BP) profiles have been reported to be independent predictors of long-term outcome in the ECASS-I. The aim is to concern these findings in the ECASS-II database.

Methods: We studied 793 patients with acute ischemic hemispheric stroke in the ECASS-II trial. After randomization, BP was measured every 15 min during the first 2 h, and every 30 min during the first 8 h, and then at one-hour interval up to 24 h. Individual 0–24 h BP profiles were characterized by baseline, maximum, minimum, mean, and successive variation (SV) of the profile. The endpoint was long-term independency (modified Rankin Scale [mRS] score of 0 or 1) at day 90.

Results: The maximum, mean and SV of systolic BP profiles were higher among those with dependent outcome, in rt-PA (p < 0.001, p < 0.001, and p = 0.006, respectively) and in placebo treated patients (p < 0.001, p < 0.001, and p = 0.07, respectively). In a logistic regression model, after adjustment for the common confounders and thrombolytic therapy, maximal systolic and diastolic BP of profiles were inversely associated with independent outcome (adjusted odds ratio [OR], 0.98; 95% CI, 0.97–0.99; and [OR], 0.97; 95% CI, 0.95–0.99 per 1 mmHg, respectively).

Conclusion: Contrary to our findings in the ECASS-I database, the improved BP management in the ECASS-II trial implied smaller within-patient BP variation, and left only peak values as prognostically significant.

Abstract ID: A0044

COMBINED CTASI-ASPECTS AND CLOT BURDEN SCALE SCORE PREDICTS SUBGROUP WITH VERY POOR PROGNOSIS DESPITE THROMBOLYSIS

V. Puetz¹, I. Dzialowski², S. Subramaniam¹, A. Krol¹, A. Demchuk¹

¹University of Calgary, Canada, ²Technical University of Dresden, Germany

Background: We tested whether combining ASPECTS on CT angiography source images (CTASI) and clot burden extent on CTA predicts the outcome in ischemic stroke.

Methods: We retrospectively studied stroke patients with disabling deficits with brain CTA < 24 h from onset. CTASI scans were scored applying ASPECTS. For clot burden score (CBS), anterior circulation arteries were allotted 10 points for presence of contrast opacification. Two points each was subtracted for absent contrast opacification in proximal M1, distal M1 or supra-clinoid ICA and 1 point each for M2 branches, A1 and infra-clinoid ICA. A combined CTASI-ASPECTS score and CBS score was evaluated for discharge independent (mRS 0–2), dependent (mRS 3–5) or fatal (mRS 6) outcomes.

Results: We identified 216 patients. Combined CTASI ASPECTS and CBS score was divided into four groups worst to best (< 10, 11–15, 16–19, 20). The proportion of independent outcome (mRS < 3) was 3%, 36%, 47%, and 48% respectively. The mortality rate was 41%, 8%, 7%, and 2% respectively. 110 patients received thrombolysis or mechanical revascularization procedures. The proportion of independent outcome (mRS < 2) was 5%, 41%, 59%, and 45% respectively. The mortality rate was 47%, 8%, 3%, and 5% respectively.

Conclusion: The combination of infarct core extent (CTASI ASPECTS) and clot burden (CBS) is a powerful and rapid method of predicting outcome acutely. The severe group with combined score < 10 is associated with a very low likelihood of independent outcome (5%) and a very high mortality rate (47%) with thrombolysis.

Abstract ID: A0047

REPERFUSION FAILURE DESPITE THROMBOLYSIS-INDUCED RECANALIZATION IN ACUTE STROKE MAY BE AN EARLY MARKER OF POOR CLINICAL OUTCOME

A.Y. Jin¹, O. Islam², F.W. Saunders², A.M. Demchuk¹, D.G. Brunet²

¹University of Calgary, Canada, ²Queen's University, Canada

Background: We assessed the hypothesis that reperfusion failure despite thrombolysis-induced recanalization is associated with a poor stroke outcome.

Methods: Patients treated with intravenous thrombolysis were considered for study enrollment. Serial NIHSS scores were evaluated throughout the hospital admission and the mRS score at three months. Serial TCD examinations were used to identify recanalization by TIBI flow grade improvement. Follow-up CT perfusion (CTP) imaging after thrombolysis permitted cerebral blood volume (CBV), cerebral blood flow (CBF) and mean transit time (MTT) map comparison between affected and contralateral hemispheres. ‘Reperfusion failure’ was defined as any region with decreased CBV, decreased CBF, and increased MTT.

Results: Of 36 patients screened, 17 patients were included in this study. The 24 h re-canalization rate was 88%. On follow-up CTP scan, 7/17 patients (41%) demonstrated reperfusion failure. Of these patients, 86% failed to show stable clinical improvement (complete resolution or improvement in NIHSS score by seven points without subsequent decline) and the median 3 month mRS score was 4. Of the 10 patients without reperfusion failure, 80% showed stable clinical improvement and the median 3-month mRS score was 1.

Conclusion: Reperfusion failure despite thrombolysis-induced re-canalization is associated a poor stroke outcome. Possible causes of reperfusion failure may include distal embolization, arterial re-occlusion, persistent branch vessel occlusion and ‘no-reflow’ phenomenon.

Abstract ID: A0007

NEUROPROTECTION BY DELPHINIUM FRACTION AGAINST THE NEURONAL HYPEREXCITABILITY

M.L. Raza, Z. Muhammad, F. Shaheen, S.U. Simjee

HEJ, ICCS, Pharmacology Unit. University of Karachi, Pakistan

Background: The Delphinium nordhagenii has never been studied for medicinal study scientifically. In the present study we have screened the actions of acetone fraction of Delphinium nordhagenii in brain excitation induced by chemoconvulsants.

Methods: Male NMRI mice weighing 20–28 g were used. The animals were divided into four test groups (GI–IV) each containing six mice. The test group I, II, III & IV received 60 mg/kg, 65 mg/kg, 70 mg/kg & 75 mg/kg i.p respectively. Four control groups were set as (CI–IV). The drug control groups (C-I & C-II) received 20 mg/kg Phenytoin and 7.5 mg/kg Diazepam, Vehicle control group (C-III) received saline and lastly no treatment was assigned as C-IV. An alternating current of 80 Hz and 80 mA was delivered to experimental animals through ear electrodes for 0.2 s. Abolishment of hind limb tonic extension and the percentage of seizure protection and mortality were recorded. And in the second phase of experimentation protocol sc PTZ test performed to induce the neuronal excitation.

Results: The acetone fraction of Delphinium nordhagenii retards the hind limb tonic extension (HLTE) and PTZ induced neuronal excitation, at the doses of 60 mg/kg, 65 mg/kg, 70 mg/kg and 75 mg/kg which were comparable to standard anti-epileptic drugs (AEDs) Phenytoin and diazepam.

Conclusion: The results of this study indicate that Delphinium nordhagenii may contains active compound that may protect the chemical induced neuronal hyper-excitability, this can be the new agent against several diseases neuronal plasticity.

Abstract ID: A0043

KIDS IDENTIFYING AND DEFEATING STROKE (KIDS): DESIGN AND PRELIMINARY DATA OF A SCHOOL BASED INTERVENTION TO IMPROVE STROKE AWARENESS

N.R. Gonzales¹, K.E. Maddox², K.M. Conley³, J.C. Grotta¹, L.B. Morgenstern²

¹University of Texas-Houston Medical School, USA, ²University of Michigan Health System, USA, ³Eastern Michigan University, USA

Background: Despite years of public education initiatives, rt-PA treatment rates remain < 5%. We report baseline data from a unique stroke education program targeted towards middle school students and their parents in an effort to increase the number of patients eligible for rt-PA treatment by increasing awareness of stroke.

Methods: KIDS is a prospective, randomized study with a specific focus on the Hispanic community. Middle schools were randomly assigned to receive either a stroke education program or the standard health class. A health education professor together with an experienced stroke treatment team designed the educational program. An interim test was given at the midpoint of the intervention. Homework was designed to deliver our educational message to the parents through the students.

Results: A total of 547 students (271 control, 276 intervention) and 484 parents (231 control, 253 intervention) were enrolled. Attrition rate between 1–2 years was 23%. Homework identified barriers to activating 911. In the intervention group, interim testing showed improvement in knowledge of stroke symptoms compared with controls.

Conclusion: Implementing a school-based stroke education initiative is feasible. Interim testing demonstrates that the intervention can improve students' knowledge of stroke. Homework assignments have identified additional targets for intervention. Follow-up testing will demonstrate whether this intervention translates into measurable and persistent improvement in stroke knowledge.

Abstract ID: A0050

MILD HYPOTHERMIA REDUCES TISSUE PLASMINOGEN ACTIVATOR-RELATED HEMORRHAGE AND BLOOD BRAIN BARRIER DISRUPTION FOLLOWING EXPERIMENTAL STROKE

LP. Liu¹, X.N. Tang², M.A. Koike², M.A. Yenari¹

¹Beijing Tiantan Hospital, Capital University of Medical

Sciences, China, ²University of California, San Francisco, USA

Background: Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) in ischemic stroke is limited by increased risks of cerebral hemorrhage and edema Therapeutic mild hypothermia is gaining considerable interest as a neuroprotectant.

Methods: Male C57B/L6 mice were subjected to MCAO for 2 h followed by 24 h reperfusion and included: TN:tPA treatment at normothermia (37 C), TH: rt-PA treatment at hypothermia (33 C), and N: no rt-PA at normothermia. rt-PA was delivered 3 h after ischemia. BBB permeability was assessed using Evan's-blue dye (EB). Infarct sizes and hemorrhagic transformation were measured. Immunostains and western blots of endogenous tPA and its inhibitor, plasminogen activator inhibitor (PAI-1) were performed in normothermic and hypothermic animals not given rt-PA.

Results: Infarct sizes in the TH group were significantly smaller than in both the TN and N groups. More BBB disruption was seen in TN compared to TH and N. Administration of exogenous rt-PA at normothermia showed a higher hemorrhagic transformation rate compared to TH and N. In mice exposed to ischemia but not given rt-PA, endogenous tPA expression was reduced in hypothermic mice, whereas PAI-1 levels were not.

Conclusion: Mild hypothermia may reduce the incidence of hemorrhagic transformation by reducing levels of endogenous tPA. In the setting of rt-PA treatment, it reduces the incidence and severity of hemorrhagic transformation and BBB disruption. Combination therapy with rt-PA should be safe, and may even improve outcome.

Abstract ID: A0060

HYPOLIPIDEMIC AND ANTI-PLATELET AGGREGATORY EFFECTS OF L-CARNITINE ON EXPERIMENTALLY INDUCED ATHEROSCLEROSIS IN ALBINO RATS

P. Kumar¹, A. Dayanandan²

¹International Medical University, Malaysia, ²Dr ALM PG IBMS, India

Background: Cerebrovascular accident is associated with increased oxidative stress and an ultimate thrombogenic tendency, dyslipidemias, circulation-dysfunction, neurological disorders in which L-Carnitine (LC) deficiency occurs. The abnormalities underlying neuropathies involve metabolic-membrane-molecular-neuronal-vasomediated defects. The purpose of this study was to determine whether administration of LC would exert hypo-lipidemic antioxidant and anti-platelet aggregatory effects in atherosclerotic rats.

Methods: Male albino rats weighing about 180–200 g were divided into three groups: a control group and saline and LC-treated atherosclerotic groups. Hyper-cholesterolemia was induced by giving atherosclerotic-diet for 4 months. A pharmacological dose (300 mg/kg b.wt, i.p in saline) of L-Carnitine was administered for 21 days, and blood was collected for the biochemical investigations at the end of the experimental period.

Results: Atherosclerotic rats elicited a significant decline in the antioxidant status and HDL-C as well as a significant increases in serum LPO, PCC, xanthine oxidase, and lipid profile and plasma fibrinogen and platelet aggregability. Supplementation of LC was effective in reduction of risk factors of Cardiovascular Diseases (CVD).

Conclusion: These results demonstrate that LC by its unique actions exerts lipotrophic, anti-peroxidative, free radicals scavenging, iron-chelating antioxidant, eicosanoids modulatory and anti-platelet aggregatory effects might be useful in prevention and repair of stroke.