Early Recurrent Stroke Research Articles

Abstract W P145: Increased Areas of Pericardial and Intrathoracic Adipose Tissue Predict Early Mortality or Recurrent Stroke and Reflect Systemic Inflammation in Patients With Ischemic Stroke

Introduction: Chronic low-grade inflammation is a recognized risk factor for all cardiovascular diseases (CVD). Of different kind of adipose tissue located in the thoracic cavity the pericardial (PAT) but not intrathoracic adipose tissue (IAT) has been shown to associate with the risk of CVD. Hypothesis: We assessed the hypothesis that increased areas of both PAT and IAT are associated with systemic inflammation, early mortality, and recurrent stroke. Methods: A total of 162 patients (69 % men, mean age 61 years) with embolic stroke of undetermined or suspected cardiogenic etiology were studied. Areas of PAT and IAT were assessed by cardiac CT performed at the time of hospital admission. Plasma levels of Interleukin (IL-) 6, IL-1, IL-10, IL-18, tumor necrosis factor (TNF) and high sensitivity CRP were assessed three months after stroke. Follow-up data of mortality and recurrent stroke was collected up to five years after the first stroke. Results: Patients who encountered death (n=18) or recurrent stroke (n=25) during the follow-up time had larger PAT (14.5 cm2 vs 11.9 cm2, p=0.041) and IAT (30.9 cm2 vs 26.1 cm2, p=0.038) areas, and also had higher plasma levels of IL-6 (p=0.047). PAT and IAT areas were associated with plasma levels of IL-6 (r=0.251; p=0.042 and r=0.287; p=0.019, respectively). Conclusions: Patients who encountered either death or recurrent stroke during the five-year follow-up period had larger areas of PAT and IAT and higher plasma levels of IL-6 suggesting that both PAT and IAT, and contiguous systemic low-grade inflammation may have a role in the pathogenesis of embolic stroke of undetermined or cardiogenic origin.

Abstract W P50: FLAIR Vessel Hyperintensity In TIA and Minor Stroke Predicts Early Recurrent Stroke

Objectives: FLAIR vessel hyperintensity (FVH) is frequently seen in patients with major acute ischemic stroke, but its significance in patients with transient ischemic attack (TIA) and minor stroke is not known. We sought to establish the prevalence of FVH in TIA and minor stroke and assess whether FVH predicts recurrent TIA or ischemic stroke. Methods: Consecutive patients from a prospective registry with high-risk TIA or minor stroke between 8/2012-7/2013 were analyzed based on these inclusion criteria: symptoms of unilateral weakness and/or speech deficit, NIHSS score ≤5, and completion of MRI within 48 hours of symptom onset. We excluded patients with isolated brainstem or cerebellar syndromes. MRI scans were reviewed by a single rater who was blinded to clinical data and used examples from published literature to score the presence of FVH and classify its location as proximal MCA, distal MCA, or PCA. After FVH rating, DWI and head and neck MRA were rated for presence of restricted diffusion and stenosis or occlusion. We employed univariable and multivariable statistics to identify independent predictors of FVH, and to examine the association between FVH and stroke recurrence. Results: Among 136 patients (mean age 69.5 ± 13.5 years; 43.4% female; 69.1% white; median NIHSS 1), 29 (21.3%) had FVH. The most common location was MCA (distal only 23; proximal only 1; distal/proximal: 3) with only 2 in the PCA. In multivariable analysis, the following variables were strongly associated with FVH: ipsilateral intracranial occlusion/stenosis (OR 13.7, 95% CI 4.8-39.2, p<0.001) and cardioembolic TOAST subtype (OR 7.4, CI 2.3-23.4, p=0.001). Neither DWI lesion nor ABCD2 score was associated with FVH. Patients with FVH were more likely to experience recurrent stroke or TIA within 90 days (17.2% vs. 1.9%; p=0.005). Conclusions: FVH is common in high-risk TIA and minor stroke patients, is associated with ipsilateral intracranial stenosis or occlusion, and strongly predicts recurrent TIA or stroke within 90 days. Since FVH did not correlate with DWI or ABCD2 scores, it should be considered in larger studies of clinical-imaging prediction tools of stroke risk after TIA and minor stroke.

Abstract W P306: Novel Oral Anticoagulant Initiation Within 14 days of Stroke Is Not Associated with Excess Hemorrhagic Transformation Rates

Introduction: The risk of early recurrent stroke after a cerebrovascular event is elevated. Despite a lack of safety data related to oral anticoagulation (OAC) after TIA/stroke in patients with atrial fibrillation (AF), particularly with respect to novel OACs (NOACs), many physicians do initiate therapy within 14 days of symptom onset. We aimed to assess current practice patterns and hemorrhagic transformation rates associated with early OAC use in AF patients. Methods: We conducted a retrospective chart review of AF patients admitted to a single stroke unit over a 24-month period. OAC agents and time from onset to initiation were recorded. Hemorrhagic transformation (HT) was assessed on CT scans and graded using the ECASS classification system (Hemorrhagic Infarction; HI and Parenchymal Hemorrhage; PH). Results: A total of 402 AF patients, with a mean age of 78.0±11.4 years (196 female), were included. OACs were initiated in 233 (58.0%) patients within 14 days of symptom onset. Of these 233 patients, warfarin was started in 136 (58.4%), dabigatran in 52 (22.3%), rivaroxaban in 40 (17.2%), and apixaban in 5 (2.1%). The median(IQR) number of days from onset to OAC initiation was similar between patients treated with warfarin (2.0(6.0)), dabigatran (2.0(3.8)), rivaroxaban (3.0(6.8)), and apixaban (3.0(5.5), P=0.44). HT was found in 10 patients, 7 (5.1%) of whom were initiated on warfarin and 3 (5.8%) on dabigatran (λ2= 2.9, P=0.14). Of the 7 warfarin related HT cases, 6 were asymptomatic HI and 1 was a symptomatic PH. All 3 dabigatran related HT cases were asymptomatic HI. HT was detected at a median of 3(4) days following OAC initiation. Systemic bleeding was seen in 7 patients, all of whom were taking warfarin (4 gastrointestinal bleeds, 2 retroperitoneal, and 1 ureteral hematoma). Conclusion: Off-label use of NOACs in acute stroke is common. Although hemorrhagic transformation rates appear to be no higher than those associated with warfarin, early NOAC initiation after stroke should be studied in a prospective fashion.

Abstract 204: Validity of Etiologic Stroke Classification: Comparison of Different Classification Systems

Background and Purpose: The goal of etiologic ischemic stroke classification is to generate determined subtypes with discrete phenotypic, therapeutic, and prognostic characteristics. Although several new etiologic classification systems have been developed in recent years, their ability to unambiguously generate discrete subtypes is not known. We prospectively examined predictive ability of TOAST, Causative Classification of Stroke System (CCS), and ASCO (based on grade-1 definitions) for various hard stroke features in 2284 consecutive patients within the context of an NIH-funded study. Methods: Three raters blinded to each other’s assignments as well as to the study end points performed subtype assignments based on information available at discharge. The primary validation end-point was 90-day stroke recurrence. Secondary validation end-points were admission infarct volume on DWI, admission NIHSS score, and 90-day mortality. We assessed predictive ability of each system by ROC analysis and determined within-category / between-category variance by calculating F values from ANOVA for continuous variables. Results: CCS demonstrated larger area under the ROC curve (AUC, 0.71, 95%CI: 0.66-0.75) for stroke recurrence when compared to ASCO (0.66, 95%CI: 0.61-0.71, p=0.04) and TOAST (0.61, 95%CI: 0.55-0.67, p<0.01). The difference in AUC between ASCO and TOAST for recurrent stroke was borderline (p=0.052). There was no difference in AUC for 90-day mortality among the systems [0.67 (95%CI, 0.63-0.70) for CCS, 0.67 (95%CI, 0.64-0.70) for ASCO, and 0.65 (95%CI, 0.62-0.68) for TOAST]. The size of undetermined category was 33% with CCS, 40% with ASCO, and 52% with TOAST (p<0.01). CCS demonstrated larger F values for admission NIHSS (41.8) and infarct volume on DWI (12.0) than ASCO (38.1, 11.4 respectively) and TOAST (37.7, 9.5 respectively). Conclusion: This study demonstrates that etiologic stroke subtypes confer predictive information for early stroke recurrence regardless of the classification system used to identify them. Our results also indicate that CCS exhibits greater capacity to generate homogenous categories with different features and assigns a larger proportion of strokes into determined subtypes as compared to other systems.

Risk of Early Recurrent Stroke in Symptomatic Carotid Stenosis

Risk of Early Recurrent Stroke in Symptomatic Carotid Stenosis

The True Risk of Early Recurrent Stroke: Importance of Cohort Composition and Index Event Definition

Guidelines for the treatment of symptomatic carotid artery disease currently recommend that carotid revascularization should be performed as soon as possible and certainly within 2 weeks of the index symptom. The underlying reason for this is growing evidence that the highest risk period for recurrent stroke is the early time period after onset of symptoms, but this must be balanced against the potential for incurring higher procedural risks. Accordingly, in the current era of better medical therapy, the key question is when exactly should interventions be performed in order to prevent recurrent stroke while not unduly increasing the procedural risk? In this retrospective study, Stromberg et al. 1 report on the risk of recurrent stroke in a population being worked up for carotid endarterectomy (CEA). The cohort consisted of all patients who were referred for ultrasound imaging and who were found to have a significant ipsilateral carotid artery stenosis. Clinical practice regarding the timing of CEA evolved over time, as is demonstrated by a reduction in the median delay from the “index symptom” to CEA of 36 days in 2005, down to a median 7 days in 2011. The authors concluded that with a 2% rate of recurrent stroke by day 2 (increasing to 4% by day 7), the risk of recurrent stroke was much lower than had been described in earlier studies, suggesting that there was maybe less need to perform emergency carotid interventions than had been previously thought. However, the reader should be aware that these findings only apply to a subgroup of patients undergoing CEA, as those with “recurrent TIAs, stroke in evolution, or worsening of symptoms” during the first few days after referral were excluded, because the authors were not convinced that these patients would benefit from acute surgery. However, to this observer, any analyses of recurrent stroke rates should include these “emergency cases”, otherwise the reported findings may simply reflect outcomes in a (biased) lower risk cohort. For example, if “stroke in evolution” patients were included, the risk of recurrent stroke at 48 hours increased from 2% to 3.2%. The second key question relates to the risk of very early revascularization. Stromberg et al. 2 recommend against

Low-molecular-weight heparin or dual antiplatelet therapy is more effective than aspirin alone in preventing early neurological deterioration and improving the 6-month outcome in ischemic stroke patients.

Background and PurposeDual antiplatelet therapy (DAT) with clopidogrel and aspirin has been shown to confer greater protection against early neurological deterioration (END) and early recurrent ischemic stroke (ERIS) than aspirin alone in patients who have experienced an acute ischemic stroke. However, few studies have compared the effects of anticoagulation therapy with low-molecular-weight heparin (LMWH), DAT, and aspirin.MethodsPatients with acute ischemic stroke (n=1,467) were randomized to therapy groups receiving aspirin (200 mg daily for 14 days, followed by 100 mg daily for 6 months), DAT (200 mg of aspirin and 75 mg of clopidogrel daily for 14 days, then 100 mg of aspirin daily for 6 months), or LMWH (4,000 antifactor Xa IU of enoxaparin in 0.4 mL subcutaneously twice daily for 14 days, followed by 100 mg of aspirin daily for 6 months). The effects of these treatment strategies on the incidence of END, ERIS, and deep-vein thrombosis (DVT) were observed for 10-14 days after treatment, and their impacts on a good outcome were evaluated at 6 months.ResultsThe DAT and LMWH were associated with a more significant reduction of END and ERIS within 14 days compared with aspirin-alone therapy. In addition, LMWH was associated with a significantly lower incidence of DVT within 14 days. At 6 months, DAT or LMWH improved the outcome among patients aged >70 years and those with symptomatic stenosis in the posterior circulation or basilar artery compared with aspirin.ConclusionsLMWH or DAT may be more effective than aspirin alone for reducing the incidence of END and ERIS within 14 days, and is associated with improved outcomes in elderly patients and those with stenosis in the posterior circulation or basilar artery at 6 months poststroke.

Risk of Early Recurrent Stroke in Symptomatic Carotid Stenosis

The risk of recurrent stroke in patients with symptomatic carotid artery stenosis is highest in the first weeks after a transient ischemic attack (TIA) or minor stroke and can be reduced with carotid endarterectomy (CEA). The optimal timing of CEA remains a controversial issue since very urgent CEA is associated with an increased procedural risk. The aim of this study was to determine the risk of very early recurrent stroke in a population with symptomatic high grade carotid stenosis. Data were analyzed on all patients with ocular TIA, TIA, or minor stroke with >70% carotid stenosis asassessed by carotid ultrasound at Sahlgrenska University Hospital during the periods 2004-2006 and 2010-2012. The two time periods were chosen to minimize selection bias and to analyze changes over time. The risk of recurrent stroke within 30 days of the referring event was assessed. 397 patients with symptomatic carotid stenosis were identified. The risk of recurrent stroke in the total cohort was 2.0% (CI 95% 0.6-3.4) by day 2, 4.0% (CI 95% 2.0-5.9) by day 7, and 7.5% (CI 95% 4.4-10.6) by day 30. There was no significant difference between the two time periods. Patients with minor stroke had a significantly higher risk of recurrent stroke than patients with TIA or ocular TIA as the referring event. The data suggest that the early risk of recurrent stroke in symptomatic significant carotid stenosis is not as high as some earlier studies have shown. The risk is similar to several studies in which a modern medical treatment regime could be assumed.

Prediction of recurrent stroke with ABCD2 and ABCD3 scores in patients with symptomatic 50-99% carotid stenosis.

BackgroundAlthough it is preferable that all patients with a recent Transient Ischemic Attack (TIA) undergo acute carotid imaging, there are centers with limited access to such acute examinations. It is controversial whether ABCD2 or ABCD3 scores can be used to triage patients to acute or delayed carotid imaging. It would be acceptable that some patients with a symptomatic carotid stenosis are detected with a slight delay as long as those who will suffer an early recurrent stroke are detected within 24 hours. The aim of this study is to analyze the ability of ABCD2 and ABCD3 scores to predict ipsilateral ischemic stroke among patients with symptomatic 50-99% carotid stenosis.MethodsIn this secondary analysis of the ANSYSCAP-study, we included 230 consecutive patients with symptomatic 50-99% carotid stenosis. We analyzed the risk of recurrent ipsilateral ischemic stroke before carotid endarterectomy based on each parameter of the ABCD2 and ABCD3 scores separately, and for total ABCD2 and ABCD3 scores. We used Kaplan-Meier analysis.ResultsNone of the parameters in the ABCD2 or ABCD3 scores could alone predict all 12 of the ipsilateral ischemic strokes that occurred within 2 days of the presenting event, but clinical presentation tended to be a statistically significant risk factor for recurrent ipsilateral ischemic stroke (p = 0.06, log rank test). An ABCD2 score ≥2 and an ABCD3 score ≥4 could predict all 12 of these strokes as well as all 25 ipsilateral ischemic strokes that occurred within 14 days. To use ABCD3 score seems preferable over the ABCD2 score because a higher proportion of low risk patients were identified (17% of the patients had an ABCD3 score <4 while only 6% had an ABCD2 < 2).ConclusionsAlthough it is preferable that carotid imaging be performed within 24 hours, our data support that an ABCD3 score ≥4 might be used for triaging patients to acute carotid imaging in clinical settings with limited access to carotid imaging. However, our findings should be validated in a larger cohort study.

Symptomatic carotid near-occlusion with full collapse might cause a very high risk of stroke.

The risk of early stroke recurrence amongst patients with symptomatic carotid near-occlusion with and without full collapse is unknown. Therefore, the aim of this study was to analyse the 90-day risk of recurrent ipsilateral ischaemic stroke in patients with symptomatic carotid near-occlusion both with and without full collapse. This study was a secondary analysis of the Additional Neurological SYmptoms before Surgery of the Carotid Arteries: a Prospective study (ANSYSCAP). We prospectively analysed 230 consecutive patients with symptomatic 50-99% carotid stenosis or near-occlusion. Based on the combination of several imaging modalities, 205 (89%) patients were classified as having 50-99% carotid stenosis, and 10 (4%) and 15 (7%) as having near-occlusion with and without full collapse, respectively. The 90-day risk of recurrent ipsilateral ischaemic stroke was compared between these three groups. Only events that occurred before carotid endarterectomy were analysed. The 90-day risk of recurrent stroke was 18% [95% confidence interval (CI) 12-25%; n=29] for patients with 50-99% carotid stenosis, 0% for patients with near-occlusion without full collapse and 43% (95% CI 25-89%; n=4) for patients with near-occlusion with full collapse (P=0.035, log-rank test). The increased risk of recurrent ipsilateral ischaemic stroke for patients with symptomatic near-occlusion with full collapse remained significant after multivariable adjustment for age, sex and type of presenting event. Patients with symptomatic carotid near-occlusion with full collapse might have a very high risk of stroke recurrence. Carotid endarterectomy could be considered for these patients.

Association of improved outcome in acute ischaemic stroke patients with atrial fibrillation who receive early antithrombotic therapy: analysis from VISTA

Ischaemic stroke patients with atrial fibrillation (AF) are at risk of early recurrent stroke (RS). However, antithrombotics commenced at the acute stage may exacerbate haemorrhagic transformation, provoking symptomatic intracerebral haemorrhage (SICH). The relevance of antithrombotics on the patterns and outcome of the cohort was investigated. A non-randomized cohort analysis was conducted using data obtained from VISTA (Virtual International Stroke Trials Archive). The associations of antithrombotics with the modified Rankin Scale (mRS) outcome and the occurrence of RS and SICH (each as a combined end-point of fatal and non-fatal events) at 90 days for post-stroke patients with AF were described. Dichotomized outcomes were also considered as a secondary end-point (i.e. mortality and good outcome measure at 90 days). In all, 1644 patients were identified; 1462 (89%) received antithrombotics, 157 (10%) had RS and 50 (3%) sustained SICH by day 90. Combined antithrombotic therapy (i.e. anticoagulants and antiplatelets), 782 (48%), was associated with favourable outcome on ordinal mRS and a significantly lower risk of RS, SICH and mortality by day 90, compared with the no antithrombotics group. The relative risk of RS and SICH appeared highest in the first 2 days post-stroke before attenuating to become constant over time. The risks and benefits of antithrombotics in recent stroke patients with AF appear to track together. Early introduction of anticoagulants (2-3 days post-stroke), and to a lesser extent antiplatelet agents, was associated with substantially fewer RS events over the following weeks but with no excess risk of SICH. More evidence is required to guide clinicians on this issue.

Floating Arterial Thrombus Related Stroke Treated by Intravenous Thrombolysis

Background: The effects of intravenous thrombolysis on floating thrombi in cervical and intracranial arteries of acute ischemic stroke patients are unknown. Similarly, the best prevention methods of early recurrences remain controversial. This study aimed to describe the clinical and radiological outcome of thrombolyzed strokes with floating thrombi. Methods: We retrospectively analyzed all thrombolyzed stroke patients in our institution between 2003 and 2010 with floating thrombi on acute CT-angiography before the intravenous thrombolysis. The floating thrombus was diagnosed if an elongated thrombus of at least 5 mm length, completely surrounded by contrast on supra-aortic neck or intracerebral arteries, was present on CT-angiography. Demographics, vascular risk factors, and comorbidities were recorded and stroke etiology was determined after a standardized workup. Repeat arterial imaging was performed by CTA at 24 h or before if clinical worsening was noted and then by Doppler and MRA during the first week and at four months. Results: Of 409 thrombolyzed stroke patients undergoing acute CT Angiography, seven (1.7%) had a floating thrombus; of these seven, six had it in the anterior circulation. Demographics, risk factors and stroke severity of these patients were comparable to the other thrombolyzed patients. After intravenous thrombolysis, the floating thrombi resolved completely at 24 h in four of the patients, whereas one had an early recurrent stroke and one developed progressive worsening. One patient developed early occlusion of the carotid artery with floating thrombus and subsequently a TIA. The two patients with a stable floating thrombus had no clinical recurrences. In the literature, only one of four reported cases were found to have a thrombolysis-related early recurrence. Conclusions: Long-term outcome seemed similar in thrombolyzed patients with floating thrombus, despite a possible increase of very early recurrence. It remains to be established whether acute mechanical thrombectomy could be a safer and more effective treatment to prevent early recurrence. However, intravenous thrombolysis should not be withheld in eligible stroke patients.

Plasma Brain Natriuretic Peptide as a Predictive Marker of Early Recurrent Stroke in Cardioembolic Stroke Patients

Whether brain natriuretic peptide (BNP) levels are associated with early recurrent stroke in cardioembolic stroke patients was investigated. From January 2010 to March 2014, consecutive patients within 24 hours of onset of cardioembolic stroke were prospectively enrolled, and admission plasma BNP levels were measured. Recurrent stroke was identified as the occurrence of additional neurologic deficits and the appearance of a new infarct on neuroimaging. Patients were divided into 2 groups: the recurrence group and the nonrecurrence group. Factors associated with stroke recurrence were investigated by multiple logistic regression analysis. A total of 348 patients were included; 17 patients (5%) had recurrent stroke during hospitalization. The median interval from stroke onset to recurrent stroke was 4 days (range, 0-30). BNP levels were significantly higher in the recurrence group than in the nonrecurrence group (304.1 vs. 206.5 pg/mL, P = .029). The optimal cutoff level, sensitivity, and specificity of BNP levels to distinguish the recurrence group from the nonrecurrence group were 255.0 pg/mL, 76%, and 60%, respectively. On multivariate analysis after adjustment for confounders, plasma BNP ≥ 255.0 pg/mL (odds ratio, 5.21; 95% confidence interval, 1.63-16.72; P = .005) was independently associated with recurrent stroke during hospitalization in cardioembolic stroke patients. Plasma BNP could be a useful marker for predicting early recurrent stroke during hospitalization in cardioembolic stroke patients.

Coated-platelets improve prediction of stroke and transient ischemic attack in asymptomatic internal carotid artery stenosis.

Coated-platelets, a subset of procoagulant platelets observed on dual agonist stimulation with collagen and thrombin, support a robust prothrombinase activity and provide a unique measure of platelet thrombotic potential. Coated-platelet levels are increased in large artery stroke, and higher levels are associated with early stroke recurrence, suggesting a potential role for risk stratification in asymptomatic patients with carotid artery stenosis. Three-hundred twenty-nine consecutive patients with technically adequate carotid Doppler evaluation without stroke or transient ischemic attack (TIA) in the previous 6 months were enrolled as part of a prospective cohort study conducted during a 40-month period. The main outcome was occurrence of stroke or TIA according to coated-platelet levels and internal carotid stenosis severity at enrollment. The optimal cutoff value of coated-platelet levels was determined by recursive partitioning analysis. Event-free survival was estimated using Kaplan-Meier and Cox proportional hazards regression analyses. A cutoff of ≥45% for coated-platelet levels in combination with stenosis≥50% yielded a sensitivity of 0.78 (95% confidence interval, 0.51-1.0), specificity of 0.92 (0.89-0.95), positive predictive value of 0.21 (0.07-0.34), and a negative predictive value of 0.99 (0.98-1.0) for ipsilateral stroke or TIA. The incidence rate of ipsilateral stroke or TIA for patients with ≥50% stenosis and ≥45% coated-platelets was 21.5 per 100 person-years versus 1.27 per 100 person-years for patients with ≥50% stenosis and <45% coated-platelets (P<0.0001). Coated-platelet levels identify asymptomatic carotid stenosis patients at high risk for stroke or TIA, which suggests a role for coated-platelets in risk stratification before revascularization.

Population-based study of blood biomarkers in prediction of subacute recurrent stroke.

Risk of recurrent stroke is high in the first few weeks after transient ischemic attack or stroke and clinical risk prediction tools have only limited accuracy, particularly after the hyperacute phase. Previous studies of the predictive value of biomarkers have been small, been done in selected populations, and have not concentrated on the acute phase or on intensively treated populations. We aimed to determine the predictive value of a panel of blood biomarkers in intensively treated patients early after transient ischemic attack and stroke. We studied 14 blood biomarkers related to inflammation, thrombosis, atherogenesis, and cardiac or neuronal cell damage in early transient ischemic attack or ischemic stroke in a population-based study (Oxford Vascular Study). Biomarker levels were related to 90-day risk of recurrent stroke as hazard ratio (95% confidence interval) per decile increase, adjusted for age and sex. Among 1292 eligible patients, there were 53 recurrent ischemic strokes within 90 days. There were moderate correlations (r=0.40-0.61; P<0.0001) between the inflammatory biomarkers and between the cell damage and thrombotic subsets. Associations with risk of early recurrent stroke were weak, with significant associations limited to interleukin-6 (adjusted hazard ratio, 1.12; 1.01-1.24; P=0.033) and C-reactive protein (adjusted hazard ratio, 1.15; 1.02-1.30; P=0.022) after adjusting for age, sex, hypertension, smoking, and diabetes mellitus although P-selectin seemed to predict stroke after transient ischemic attack (adjusted hazard ratio, 1.28; 1.00-1.63; P=0.046). In the largest study to date, we found limited predictive use for early recurrent stroke for a panel of inflammatory, thrombotic, and cell damage biomarkers.

Recurrence in Intracranial Atherosclerotic Disease: A Stenosis-based Analysis

Intracranial atherosclerotic disease is a common cause of stroke; its incidence and prevalence vary widely by ethnicity. The aim of our study was to analyze the recurrence rate of cerebrovascular events in patients with symptomatic and asymptomatic intracranial stenosis (IS). We conducted a historical cohort study including all patients admitted in our hospital for stroke or transient ischemic attack (TIA) during 2011 and 2012 with information on intracranial circulation (ultrasonography and/or computed tomography angiography). We identified patients with symptomatic and asymptomatic IS and studied the recurrence of cerebrovascular events (TIA or ischemic stroke within the territory of the stenosis) for a minimum follow-up period of 6 months after the diagnosis of IS. For the recurrence rate estimation, patients with other potentially embolic diseases (in cervical arteries or heart) were excluded. We calculated the rate of recurrence of cerebrovascular events and performed Kaplan-Meier survival curves for symptomatic and asymptomatic IS. We investigated 1302 patients, mean age was 72.41 years (standard deviation 12.75). We identified 218 IS in 158 patients, 77 were symptomatic and 141 were asymptomatic. The recurrence rate of cerebrovascular events was 12.32 per 100 patient-years, with a mean time to recurrence of 1.73 months for symptomatic intracranial stenosis (SIS) and .88 per 100 patient-years for asymptomatic IS (P < .001). These results indicate a high risk of early recurrence of stroke in the territory of a SIS, highlighting the importance of its early diagnosis and aggressive treatment.

Ischämischer Insult – Diagnostik und Therapie

Management of ischemic stroke is targeted on four therapeutic objectives: limitation of neurological deficit, prevention of earyl stroke recurrence, protection against complications, and secondary prevention. Intravenous thrombolysis within 4.5h of stroke onset is the only proven therapy to improvefunctional outcome. Although promising, neither endovascular recanalisation nor neuroprotective strategies have demonstrated efficacy so far. Immediate administration of antiplatelet agents like acetylsalicylic acid and clopidogrel - in case of intravenous thrombolysis at the earliest after 24h - is effective to prevent early stroke recurrence, whereas anticoagulants should be ommitted in this stage because of an increased risk of cerebral hemorrhage. Subcutaneous heparin/low molecular weight heparin, mobilisation, nasogastric tube, and decompressive craniectomy may protect from venous thromboembolism, aspiration pneumonia, and malignant brain edema, respectively. Secondary prevention is guided by stroke etiology, e.g. oral anticoagulation in the presence atrial fibrillation or endarterectomy in case of sympomatic high-grade carotid stenosis.

Oral antiplatelet therapy for acute ischaemic stroke.

In people with acute ischaemic stroke, platelets become activated and can cause blood clots to form and block an artery in the brain, resulting in damage to part of the brain. Such damage gives rise to the symptoms of stroke. Antiplatelet therapy might reduce the volume of brain damaged by ischaemia and also reduce the risk of early recurrent ischaemic stroke, thereby reducing the risk of early death and improving long-term outcomes in survivors. However, antiplatelet therapy might also increase the risk of fatal or disabling intracranial haemorrhage. To assess the efficacy and safety of immediate oral antiplatelet therapy (that is started as soon as possible and no later than two weeks after stroke onset) in people with acute presumed ischaemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched 16 October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2013), MEDLINE (June 1998 to May 2013), and EMBASE (June 1998 to May 2013). In 1998, for a previous version of this review, we searched the register of the Antiplatelet Trialists' Collaboration, MedStrategy and contacted relevant drug companies. Randomised trials comparing oral antiplatelet therapy (started within 14 days of the stroke) with control in people with definite or presumed ischaemic stroke. Two review authors independently applied the inclusion criteria and assessed trial quality. For the included trials, they extracted and cross-checked the data. We included eight trials involving 41,483 participants. No new trials have been added since the last update.Two trials testing aspirin 160 mg to 300 mg once daily, started within 48 hours of onset, contributed 98% of the data. The risk of bias was low. The maximum follow-up was six months. With treatment, there was a significant decrease in death or dependency at the end of follow-up (odds ratio (OR) 0.95, 95% confidence interval (CI) 0.91 to 0.99). For every 1000 people treated with aspirin, 13 people would avoid death or dependency (number needed to treat 79). Antiplatelet therapy was associated with a small but definite excess of symptomatic intracranial haemorrhages, but this small hazard was significantly outnumbered by the benefit, the reduction in recurrent ischaemic stroke and pulmonary embolus. Antiplatelet therapy with aspirin 160 mg to 300 mg daily, given orally (or by nasogastric tube or per rectum in people who cannot swallow) and started within 48 hours of onset of presumed ischaemic stroke, reduced the risk of early recurrent ischaemic stroke without a major risk of early haemorrhagic complications; long-term outcomes were improved.

Abstract W P141: Cerebral Microbleeds and White Matter Hyperintensities as Predictors for Early Stroke Recurrences in Transient Ischemic Attack: Korean TIA eXpression Study

Background: Patients within 24 hours from symptom onset of transient ischemic attack (TIA) are particularly at high risk of early recurrent stroke. Neuroimaging variables are increasingly recognized to help better identify patients at high risk. The Korean TIA eXpression study aimed to determine the risk of early recurrent stroke and its clinical and imaging predictors. Methods: We conducted a hospital-based, multi-center prospective cohort study. TIA was defined by transient focal neurological deficits which result from ischemia and last less than 24 hours. Inclusion criteria were: 1) patients who admitted within 24 hours after symptom onset, 2) those who underwent magnetic resonance imaging and angiography, and 3) age of 45 years or older. We collected baseline data of demographics, vascular risk factors, clinical manifestation, potential mechanism of TIA, neuroimaging findings of acute ischemic lesions, white matter changes, microbleeds, vascular status, and laboratory test results. The primary endpoint was recurrent stroke within 90 days. Results: A total of 500 patients (mean age 64.4, male 58%, mean ABCD2 score 4.3 ± 1.4) were enrolled and completed 90-day follow-up. The primary endpoint of recurrent stroke developed in 25 (5.0%) patients within 90 days. From univariable analyses, we identified the following potential predictors (p &lt; 0.20) of recurrent stroke within 90 days: ABCD2 scores, crescendo TIA, lacunar TIA, symptomatic extracranial occlusion, old lacune, white matter hyperintensities, and cerebral microbleeds. In a multivariable logistic regression analysis, crescendo TIA (adjusted odds ratio (OR) 4.4, 95% confidential interval (CI) 1.3-14.7), lacunar TIA (OR 2.5, 95% CI 1.1-6.1), white matter hyperintensities (OR 2.4, 95% CI 1.1-5.4), and cerebral microbleeds (OR 4.9, 95% CI 1.9-12.8) were independently associated with recurrent stroke within 90 days. Conclusion: In conclusion, the current study suggests that microangiopathy may be a predictor for early recurrent strokes after TIA. Our novel findings need to be validated in future studies.

Abstract W P241: Early Anti-Coagulation in Acute Cardio-Embolic Stroke is Safe But Does Not Prevent Recurrent Stroke: A Single Centre Review

Background: Atrial fibrillation is the most common arrhythmia in older adults and a common cause of stroke. Patients with acute cardio-embolic stroke from atrial fibrillation are at high risk for recurrence with up to 50% of recurrent stroke occurring within 2 weeks of the index event. Anti-coagulation with heparinoids within 48 hours of stroke has been shown to increase risk of symptomatic intracranial hemorrhage (ICH) with no clear benefit on early stroke recurrence. Methods: This study was a retrospective chart review of consecutive patients who were admitted to the stroke service at the Foothills Medical Centre between 2009 and 2011. All patients with an acute stroke with a cardio-embolic etiology and a diagnosis of atrial fibrillation either by history or on electrocardiogram within two years of stroke were reviewed. We hypothesized that anti-coagulation within two weeks of stroke, appropriately begun because of a diagnosis of atrial fibrillation, decreased rates of recurrent stroke without causing an increase in rates of symptomatic ICH. Results: During the three-year period 324 patients were identified with cardio-embolic stroke secondary to atrial fibrillation. Within two weeks of stroke onset 63.0% (203/324) of patients were therapeutic on anti-coagulation with warfarin being the most common anti-coagulant used (67.6%). Patients who were anti-coagulated had a smaller mean stroke volume (18.9 cc vs 49 cc) and lower mean NIHSS at presentation (7 vs 9) but otherwise did not differ in baseline characteristics. Three (0.9%) patients had a clinically significant ICH; only one patient was actively anti-coagulated at the time of ICH, one was taking aspirin only and one was on aspirin and low dose enoxaparin for prevention of deep vein thrombosis. Recurrent stroke occurred in 16 patients (4.9%) within the two-week period. Anti-coagulation did not significantly reduce the risk of recurrent stroke (RR 0.67 95% CI 0.19 - 2.36). Conclusion: Anti-coagulation within 2 weeks of acute stroke in patients with atrial fibrillation appears to be safe among patients with smaller infarcts. Large studies would be needed to show if anticoagulation actually reduced the rate of early recurrent cardioembolic stroke.