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Objective: The aim of this systematic review and meta-analysis was to evaluate the safety and efficacy of IV thrombolysis (IVT) with tissue plasminogen activator (tPA) delivered through telestroke networks in patients with acute ischemic stroke. Methods: We conducted a systematic review and meta-analysis according to PRISMA guidelines. Literature searches on MEDLINE, Embase, and CENTRAL databases covered prospective randomized controlled and nonrandomized studies comparing telemedicine-guided IVT to IVT administered at stroke centers and were published from the earliest date available until April 1, 2015. Outcomes of interest were symptomatic intracerebral hemorrhage, mortality, and functional independence (modified Rankin Scale scores 0–1) at 3 months. Random-effects meta-analysis was used to compute pooled effect estimates and the I 2 statistic to assess heterogeneity. Results: Of 529 records identified, 7 studies totaling 1,863 patients fulfilled our eligibility criteria. Among these, thrombolysis was largely restricted to the 3-hour time window. Symptomatic intracerebral hemorrhage rates were similar between patients subjected to telemedicine-guided IVT and those receiving tPA at stroke centers (risk ratio [RR] = 1.01, 95% confidence interval [CI] 0.37–2.80; p = 0.978) with low evidence of heterogeneity ( I 2 = 37%; p = 0.189). There was no difference in mortality (RR = 1.04, 95% CI 0.74–1.48; p = 0.806) or in functional independence (RR = 1.11, 95% CI 0.78–1.57; p = 0.565) at 3 months between telemedicine-guided and stroke center thrombolysis. No heterogeneity was identified ( I 2 = 0%, p = 0.964 and I 2 = 52%, p = 0.123, respectively). Conclusions: Our findings indicate that IV tPA delivery through telestroke networks is safe and effective in the 3-hour time window. Lack of prospective trials, however, emphasizes the need to further substantiate these findings in the 3- to 4.5-hour time window. PROSPERO registration information: URL: http://www.crd.york.ac.uk/PROSPERO. Unique identifier: CRD42015017232.

Background The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear. Purpose In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation. Methods In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke. Results A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24–2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74–2.04)). Conclusions After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its pattern, is determinant for recurrence.

Aims Variability in responsiveness to clopidogrel is a clinical problem in secondary prevention after cerebral ischaemia which has been suggested to be linked to competitive metabolization of clopidogrel and cytochrome P450 (CYP) 3A4-oxidated statins such as simvastatin. We assessed the hypothesis that simvastatin, in contrast to CYP 2C9-metabolized fluvastatin, reduces clopidogrel-mediated platelet inhibition. Methods We performed a randomized, double-blind, double-dummy, two period crossover study in 13 patients with cerebral ischaemia (8F, 5 M), aged 64.1 ± 8.0 years (mean ± SD). After a 14 day period in which all patients received 75 mg clopidogrel day−1, patients additionally received either 20 mg simvastatin day−1 or 80 mg fluvastatin day−1 for 14 days. Regimens were crossed over after a 14 day wash-out period and switched regimens were continued for another 14 days. Platelet aggregation, clopidogrel active metabolite (CAM) plasma concentrations and routine laboratory parameters including prothrombin time (PT) Quick percent value were assessed at baseline and following each treatment phase. Results Clopidogrel reduced platelet aggregation in all patients as expected. Platelet aggregation and CAM plasma concentrations were unaltered when simvastatin or fluvastatin was added to clopidogrel. Simvastatin decreased PT Quick percent value (decrease from 109 ± 10.5% to 103 ± 11%, P < 0.05) when combined with clopidogrel but there was no such change following treatment with fluvastatin and clopidogrel. Conclusions Our data indicate that treatment with CYP 3A4-metabolized simvastatin does not jeopardize clopidogrel-mediated inhibition of platelet aggregation. After co-administration of simvastatin and clopidogrel we observed a decrease in the PT Quick percent value which could be due to simvastatin-induced reduction of activity of prothrombin fragment 1 + 2.

Background and Purpose: The aim of this study was to investigate for a possible association between both prestroke CHA(2)DS(2)-VASc score and the severity of stroke at presentation, as well as disability and mortality at 90 days, in patients with acute stroke and atrial fibrillation (AF). Methods: This prospective study enrolled consecutive patients with acute ischemic stroke, AF, and assessment of prestroke CHA2DS2-VASc score. Severity of stroke was assessed on admission using the National Institutes of Health Stroke Scale (NIHSS) score (severe stroke: NIHSS >= 10). Disability and mortality at 90 days were assessed by the modified Rankin Scale (mRS = 3). Multiple logistic regression was used to correlate prestroke CHA(2)DS(2)-VASc and severity of stroke, as well as disability and mortality at 90 days. Results: Of the 1020 patients included in the analysis, 606 patients had an admission NIHSS score lower and 414 patients higher than 10. At 90 days, 510 patients had mRS >= 3. A linear correlation was found between the prestroke CHA(2)DS(2)-VASc score and severity of stroke (P = .001). On multivariate analysis, CHA(2)DS(2)-VASc score correlated with severity of stroke (P = .041) and adverse functional outcome (mRS = 3) (P = .001). A logistic regression with the receiver operating characteristic graph procedure (C-statistics) evidenced an area under the curve of .60 (P = .0001) for severe stroke. Furthermore, a correlation was found between prestroke CHA(2)DS(2)-VASc score and lesion size. Conclusions: In patients with AF, in addition to the risk of stroke, a high CHA(2)DS(2)-VASc score was independently associated with both stroke severity at onset and disability and mortality at 90 days.

Background and Purposes— This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods— The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00–1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08–2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P =0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30–1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632–0.763; P =0.0001) for ischemic outcome events and 0.585 (0.493–0.678; P =0.10) for major bleedings. Results— The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529–0.763; P =0.009) for ischemic outcome events and 0.407 (0.275–0.540; P =0.14) for hemorrhagic outcome events. Conclusions— In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings.

Objectives Transesophageal echocardiography (TEE) is the diagnostic gold standard for the detection of structural heart diseases as potential sources of cardiac emboli in patients with acute cerebral ischemia. We sought to determine the diagnostic yield of TEE in patients with acute ischemic stroke or transient ischemic attack (TIA). Methods We retrospectively analyzed consecutive patients with acute cerebral ischemia who were admitted to our hospital between October 2008 and December 2011. TEE reports were screened for detection of cardiac source of embolism judged by the recommendation to change medical management. We performed univariate and multivariate analyses to identify predictors of clinically relevant TEE findings among baseline characteristics. Results Of 3314 patients with ischemic stroke or TIA, TEE was performed in 791 (24%) patients (mean age 64 ± 13 years, 589 [74%] ischemic stroke, 202 [26%] TIA). A potential cardioembolic source was found in 71 (9%) patients with patent foramen ovale with atrial septal aneurysm being the most common finding (24/71 patients, 34%). In multivariate analysis, peripheral vascular disease (OR 2.57; 95%CI 1.00–6.61), imaging evidence of infarction in multiple locations (OR 4.13; 95%CI 1.36–12.58), and infarction in the posterior circulation (OR 2.11; 95%CI 1.01–4.42) were associated with the identification of a potential cardioembolic source with TEE. Conclusion TEE identified a potential structural cardioembolic source in nearly 10% of our selected patient population with acute ischemic stroke or TIA, thus underlining its diagnostic value. Our data suggest that patients with hitherto unknown stroke etiology should be considered for additional TEE.

Early screening for sleep apnea (SA) is rarely considered in patients with acute cerebral ischemia. We aimed to evaluate the feasibility of early SA screening on a stroke unit, its impact on post-discharge SA care and the relation of SA to clinical features. Patients with acute ischemic stroke (AIS) and transient ischemic attack (TIA) prospectively underwent overnight cardiorespiratory polygraphy within 3 ± 2 days of symptom-onset. Feasibility was defined as analyzable polygraphy in 90 % of studied patients. We enrolled 61 patients (84 % AIS, 16 % TIA): mean age 66 ± 8 years, 44 % men, median NIHSS 1 (0–15), median ESS 5 (0–13). Analyzability was given in 56/61 (91.8 %; one-sided 95 % CI, lower-bound 86.0 %) patients indicating excellent feasibility of early SA screening with no significant differences in stroke severity (100 % in TIA, 91 % minor stroke, 83 % major stroke, p = 0.474). Ninety-one percent (51/56) had an apnea–hypopnea index ≥5/h (median: 20/h [0–79]); 32 % (18/ 56) mild, 30 % (17/56) moderate, and 29 % (16/56) severe SA. When comparing sleep-related ischemic stroke (SIS) and non-SIS patients, no differences were found regarding the presence (95 vs. 89 %, p = 0.49) or severity (e.g., severe SA: 32 vs. 27 %, p = 0.69) of SA. After 12 months, 27/38 (71 %) patients given specific recommendations completed in-laboratory sleep work-up and 7/27 (25 %) were prescribed for non-invasive ventilatory correction. In conclusion, early SA screening is feasible in patients with acute cerebral ischemia and may have a positive impact on post-discharge SA care. Given the high frequency and atypical presentation of SA, early screening for SA should be considered in all acute cerebral ischemia patients.

BACKGROUND The best therapeutic approach in patients with acute basilar artery occlusion (BAO) remains unclear. We report the results of a combined treatment approach with intravenous (IV) abciximab and intraarterial (IA) tissue plasminogen activator (tPA) in these patients. METHODS We prospectively studied patients with acute BAO on CT-angiography or MR-angiography. We treated patients with IV abciximab followed by IA thrombolysis with tPA. Primary outcome was partial or complete recanalization according to thrombolysis in myocardial infarction 2 to 3 flow grades on catheter angiography. Secondary outcomes were favorable functional outcome (mRS score ≤3) and mortality at 90 days. RESULTS Of 20 patients, mean age was 62 ± 13 years, median baseline National Institutes of Health Stroke Scale (NIHSS) score 25.5 (IQR 12-28), and median Glasgow Coma Scale score 7 (IQR 6-11). Mean time to IA treatment was 7 ± 2.8 hours. We achieved partial or complete recanalization in 17/20 patients (85%). At 3 months, 3/20 patients (15%) had a favorable functional outcome and 9/20 patients (45%) were deceased. CONCLUSIONS Combined treatment with IV abciximab and IA tPA yielded a high recanalization rate in patients with BAO. However, functional outcomes were poor, potentially due to late initiation of treatment. Early treatment might improve functional outcome. J Neuroimaging 2012;22:167–171.

Introduction: Our ongoing post-stroke care program aims at risk factors control, life-style changes and adherence to secondary prevention medication to reduce stroke recurrence and persistent disability. Methods: Consecutive acute ischemic and hemorrhagic stroke patients were prospectively included in a 1-year post stroke care program that is accomplished through a certified stroke case manager. Scheduled and non-scheduled personal contacts were regularly provided to check on risk factor control and whenever felt necessary. Target values for vascular risk factors followed current recommendations of the European stroke guidelines. Results: Between 12/2011 and 07/2014 we enrolled 101 of 155 screened patients: 58/101 (57%) were male, mean age was 71+/-13 years, median baseline NIHSS score was 2 (range 0-16), 80/101 (79%) had an ischemic stroke, 3/101 (3%) hemorrhagic stroke and 18/101 (18%) patients had a TIA. Twelve out of 101 patients withdrew from the program and three patients died due to non-vascular causes. In total 628 personal (6.2/patient) and 2683 phone contacts (26.6/patient) were conducted by the case manager. Three hundred-seventy nine specific interventions were necessary mostly due to missing medication, non-compliance and social needs. No recurrent stroke occurred during the program. Achieved vascular risk factor values are presented in the Table. Conclusion: Our findings underline that organized post-stroke care may aid in achieving pre-defined goals for secondary prevention of stroke. Further data is needed to explore its impact on stroke recurrence, prevention of persistent disability and health-care costs.

Introduction: The aim of the present systematic review and meta-analysis was to evaluate the safety and efficacy of intravenous thrombolysis with tissue plasminogen activator (tPA) delivered through telestroke networks in patients with acute cerebral ischemia. Methods: We conducted a systematic review and meta-analysis according to PRISMA guidelines of all available randomized controlled and prospective non-randomized studies that compared telemedicine-guided thrombolysis to either phone-guided or on-site thrombolysis. Outcomes of interest were mortality and favorable functional outcome (i.e., modified Rankin scale 0-1) at 90-days and any tPA-associated intracerebral hemorrhage. Fixed-effect model was used to compute pooled effect estimates and the I2 statistic was used to assess heterogeneity. Results: Of 529 records identified through database searching, only five studies with a total of 1,562 patients fulfilled our eligibility criteria. Intracerebral hemorrhage rates were similar between patients subjected to telemedicine-guided thrombolysis and those receiving tPA after phone consultation or on-site at a stroke center (odds ratio=0.68, 95%CI: 0.36-1.26; p=0.216) with no evidence of heterogeneity (I2=0%). Neither there was a difference in mortality (odds ratio=1.17, 95%CI: 0.85-1.61; p=0.328) nor in favorable functional outcome (odds ratio=1.24, 95%CI: 0.83-1.86; p=0.291) at 90-days between telemedicine-guided thrombolysis and phone-guided or on-site thrombolysis. There was evidence of low heterogeneity (I2=29% and 37%, respectively; p>0.1). No evidence of publication bias (p>0.1, Egger statistical test) was detected. Conclusions: Our findings indicate that intravenous tPA delivery through telestroke networks is safe and effective. Lack of prospective trials, however, emphasize the need to further substantiate these findings in studies with sound methodological quality.

Introduction: To determine the diagnostic agreement between manual and semi-automated vessel analysis software measurements of extracranial internal carotid artery (ICA) steno-occlusive disease on CT-angiography (CTA). Methods: We studied consecutive patients with acute cerebral ischemia who were admitted (01/2012 to 12/2012) to our academic stroke center and underwent CTA for routine evaluation of stroke. NASCET-type percent stenosis was independently assessed on axial CTA source images by 1) manual caliper measurements and, 2) the semi-automated vessel analysis software syngo®.via (Siemens Healthcare, Germany) that provides area stenosis estimates. To correspond to clinically relevant NASCET strata, all stenosis measurements were stratified into ranges: normal, 1-49%, 50-69%, 70-99%, and occlusion. Results: A total of 330 patients (age 72±12yrs; 58% men; median NIHSS 4, interquartile range 8) provided 647 vessel pairs for comparative analysis. Manual caliper measurements revealed 50-69% stenosis in 29, 70-99% stenosis in 6 and occlusion in 34 internal carotid arteries, while semi-automated vessel analysis detected 50-69% stenosis in 27, 70-99% stenosis in 14 and occlusion in 34 internal carotid arteries (p=0.003). Bland-Altman analysis showed a mean difference of 1.55% in the degree of stenosis between both methods with lower and upper limits of agreement of -16.7 to 19.8%. Conclusions: Although we found an overall good agreement between both stenosis grading methods, the semi-automated vessel software analysis seems to overcall the stenosis in severe ranges when compared with manual caliper measurements.

Introduction: Novel multi-parametric criteria for duplex ultrasonography (DUS) grading of extracranial internal carotid artery (ICA) steno-occlusive disease have been recently introduced by the German ultrasound expert panel (DEGUM). We sought to determine diagnostic accuracy of the DEGUM criteria against the gold standard catheter angiography. Methods: We prospectively enrolled consecutive patients who routinely underwent diagnostic or therapeutic catheter angiography of the extracranial carotid arteries in four German study sites. Internal carotid artery disease was graded according to the DEGUM multi-parametric criteria for DUS. On angiography, extracranial ICA disease was graded using the NASCET approach. Ultrasonography and endovascular raters were blinded to clinical data and any other imaging modalities. To correspond to clinically relevant NASCET groups, all stenosis measurements were stratified into ranges: normal, mild (1-49%), moderate (50-69%), severe (70-99%) and occlusion. Results: We studied 130 patients who underwent both DUS and catheter angiography for assessment of carotid arteries (mean age, 64±11 years; 67% men; median time between DUS and angiography, 1 day [interquartile range, 2.5]). To date, fifty-two carotid artery pairs were independently rated and available for comparative analysis. Compared with catheter angiography, DUS had the following positive (PPV) and negative predictive values (NPV): PPV 50% and NPV 72% (3 true positive, 3 false positive, 33 true negative, 13 false negative) for detection of moderate, and PPV 57% and NPV 77% (20 true positive, 15 false positive, 13 true negative, 4 false negative) for detection of severe stenosis. Conclusions: Our preliminary data indicate that the novel DEGUM multi-parametric ultrasonography criteria do not eliminate the need for a confirmatory test for identification of clinically relevant grades of extracranial ICA disease.

Introduction: Elevated arterial blood pressure (BP) increases the risk of intracerebral hemorrhage after intravenous (IV) thrombolysis with tPA in acute ischemic stroke (AIS). While arterial BP is usually monitored using intermittent oscillometric measurements with an upper arm cuff, the vascular unloading technique (VUT) provides non-invasive continuous BP monitoring with a finger cuff. Hypothesis: We hypothesized that VUT monitoring is feasible in AIS patients receiving IV tPA, is comparable to the standard technique, and allows detection of BP peaks that might be missed in oscillometric BP monitoring. Methods: We performed an interim analysis of an ongoing prospective method comparison study. AIS patients were simultaneously monitored over 24 h following IV tPA bolus using VUT and contralateral oscillometric BP assessment every 30 min. Results: We present interim data from 15 out of 24 AIS (4 m, 11 f; aged 72.5±14.9 y, mean±SD) receiving IV tPA. Nominal significance level was set to 0.029 in accordance with Pocock’s rule. Missing data were less than 5% for both techniques. There was a positive correlation between VUT and oscillometric BP assessment (Pearson’s correlation coefficient r=0.91, p180 or diastolic BP>110 mmHg) were detected by VUT monitoring (at least one episode≥5 min) in 12 patients, and by oscillometric BP assessment (≥one time point of measurement) in 7 patients (p Conclusions: Our interim data suggest that VUT-based BP monitoring is feasible in AIS patients receiving IV tPA, and might be more sensitive than intermittent oscillometric BP assessment in detecting potentially harmful blood pressure peaks. Figure 1: Bland Altman plot

Anticoagulant therapy is recommended for the secondary prevention of stroke in patients with atrial fibrillation (AF). T he identification of patients at high risk for early recurrence, which are potential candidates to prompt anticoagulation, is crucial to justify the risk of bleeding associated with early anticoagulant treatment. The aim of this study was to evaluate in patients with acute ischemic stroke and AF the association between findings at trans-thoracic echocardiography (TTE) and 90 days recurrence. In consecutive patients with acute ischemic stroke and AF, TTE was performed within 7 days from hospital admission. Study outcomes were recurrent ischemic cerebrovascular events (stroke or TIA) and systemic embolism. 854 patients (mean age 76.3 +/- A 9.5 years) underwent a TTE evaluation; 63 patients (7.4 %) had at least a study outcome event. Left atrial thrombosis was present in 11 patients (1.3 %) among whom 1 had recurrent ischemic event. Left atrial enlargement was present in 548 patients (64.2 %) among whom 51 (9.3 %) had recurrent ischemic events. The recurrence rate in the 197 patients with severe left atrial enlargement was 11.7 %. On multivariate analysis, the presence of atrial enlargement (OR 2.13; 95 % CI 1.06-4.29, p = 0.033) and CHA(2)DS(2)-VASc score (OR 1.22; 95 % CI 1.04-1.45, p = 0.018, for each point increase) were correlated with ischemic recurrences. In patients with AF-associated acute stroke, left atrial enlargement is an independent marker of recurrent stroke and systemic embolism. The risk of recurrence is accounted for by severe atrial enlargement. TTE-detected left atrial thrombosis is relatively uncommon.

Introduction Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation” (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0–2 favorable outcome, 3–6 unfavorable outcome). Results Of the 1029 patients enrolled, 561 were women (54.5%) ( p Conclusions Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes.

Background Recent studies showed that the safety and benefit of early intravenous (IV) thrombolysis on favourable outcomes in acute ischemic stroke are also seen in the elderly. Furthermore, it has shown that age increases times for pre- and in-hospital procedures. We aimed to assess the applicability of these findings to telestroke. Methods We retrospectively analysed 542 of 1659 screened consecutive stroke patients treated with IV thrombolysis in our telestroke network in East-Saxony, Germany from 2007 to 2012. Outcome data were symptomatic intracranial hemorrhage (sICH) by ECASS-2-criteria, survival at discharge and favourable outcome, defined as a modified Rankin scale (mRS) of 0–2 at discharge. Results Thirty-three percent of patients were older than 80 years (elderly). Being elderly was associated with higher risk of sICH ( p = 0.003), less favourable outcomes ( p = 0.02) and higher mortality ( p = 0.01). Using logistic regression analysis, earlier onset-to-treatment time was associated with favourable outcomes in not elderly patients (adjusted odds ratio (OR) 1.18; 95% CI 1.03–1.34; p = 0.01), and tended to be associated with favourable outcomes (adjusted OR 1.13; 95% CI 0.92–1.38; p = 0.25) and less sICH (adjusted OR 0.88; 95% CI 0.76–1.03; p = 0.11) in elderly patients. Age caused no significant differences in onset-to-door-time ( p = 0.25), door-to-treatment-time ( p = 0.06) or onset-to-treatment-time ( p = 0.29). Conclusion Treatment time seems to be critical for favourable outcome after acute ischemic stroke in the elderly. Age is not associated with longer delivery times for thrombolysis in telestroke.

The aim of this study was to investigate for a possible association between both prestroke CHAThis prospective study enrolled consecutive patients with acute ischemic stroke, AF, and assessment of prestroke CHAOf the 1020 patients included in the analysis, 606 patients had an admission NIHSS score lower and 414 patients higher than 10. At 90 days, 510 patients had mRS ≥3. A linear correlation was found between the prestroke CHAIn patients with AF, in addition to the risk of stroke, a high CHA

The German Society of Ultrasound in Medicine (known by its acronym DEGUM) recently proposed a novel multi-parametric ultrasound approach for comprehensive and accurate assessment of extracranial internal carotid artery (ICA) steno-occlusive disease. We determined the agreement between duplex ultrasonography (DUS) interpreted by the DEGUM criteria and CT angiography (CTA) for grading of extracranial ICA steno-occlusive disease. Consecutive patients with acute cerebral ischemia underwent DUS and CTA. Internal carotid artery stenosis was graded according to the DEGUM-recommended criteria for DUS. Independent readers manually performed North American Symptomatic Carotid Endarterectomy Trial-type measurements on axial CTA source images. Both modalities were compared using Spearman’s correlation and Bland-Altman analyses. A total of 303 acute cerebral ischemia patients (mean age, 72 ± 12 years; 58 % men; median baseline National Institutes of Health Stroke Scale score, 4 [interquartile range 7]) provided 593 DUS and CTA vessel pairs for comparison. There was a positive correlation between DUS and CTA (r s = 0.783, p

Background Several clinical studies have indicated that selective serotonin reuptake inhibitors (SSRIs) administered in patients after acute ischemic stroke can improve clinical recovery independently of depression. Due to small sample sizes and heterogeneous study designs interpretability was limited in these studies. The mechanisms of action whereby SSRI might improve recovery from acute ischemic stroke are not fully elucidated. Methods We searched MEDLINE using the PubMed interface to identify evidence of SSRI mediated improvement of recovery from acute ischemic stroke and reviewed the literature on the potential underlying mechanisms of action. Results Among identified clinical studies, a well‐designed randomized, double‐blind, and placebo‐controlled study (FLAME ‐ fluoxetine for motor recovery after acute ischemic stroke) demonstrated improved recovery of motor function in stroke patients receiving fluoxetine. The positive effects of SSRIs on stroke recovery were further supported by a meta‐analysis of 52 trials in a total of 4060 participants published by the Cochrane collaboration. Based on animal models, the mechanisms whereby SSRIs might ameliorate functional and structural ischemic‐brain damage were suggested to include stimulation of neurogenesis with migration of newly generated cells toward ischemic‐brain regions, anti‐inflammatory neuroprotection, improved regulation of cerebral blood flow, and modulation of the adrenergic neurohormonal system. However, to date, it remains speculative if and to what degree these mechanisms convert into humans and randomized controlled trials in large populations of stroke patients comparing different SSRIs are still lacking. Conclusion In addition to the need of comprehensive‐clinical evidence, further elucidation of the beneficial mechanisms whereby SSRIs may improve structural and functional recovery from ischemic‐brain damage is needed to form a basis for translation into clinical practice.

Background Low adherence to secondary prevention guidelines in stroke survivors may increase the risk for recurrent stroke and adversely impact quality of life. We aimed to determine the feasibility of a self-developed standardized post-stroke pathway and its impact on secondary stroke prevention and long-term outcome in patients with acute stroke. Methods Consecutive patients with acute stroke were prospectively included in a standardized post-stroke pathway accomplished through a single certified CM (case manager), which comprised educational discussions and quarterly checkups for vascular risk factors and adherence to antithrombotic/anticoagulant medication in addition to usual care. At 12 months, we compared achieved target goals for secondary prevention, functional outcome, stroke recurrence, and vascular death with age- and gender-matched controls that received only usual care after stroke. Results We included 45 cases and 45 controls. The following target goals were more frequently achieved in CM-patients than in controls: blood pressure (100% vs. 46.2%, P

Acute ischemic stroke (AIS) patients receiving non-vitamin-K antagonist oral anticoagulants (NOAC) are commonly excluded from thrombolytic therapy, as interpretation of coagulation tests remains unclear. We aimed to investigate the applicability of a novel institutional protocol for thrombolysis based on current expert recommendations and NOAC specific coagulation assessment. We included hospitalized AIS patients receiving NOAC for at least 24 h and consecutive AIS patients not receiving NOAC into a prospective study. We performed standard coagulation tests and specific tests for dabigatran, rivaroxaban and apixaban plasma levels. We studied 65 patients: mean age 72 ± 13 years, 30 (46 %) male, median NIHSS score 3 (IQR 6). Fifteen (23 %) were on NOAC treatment (5 dabigatran, 5 rivaroxaban, and 5 apixaban, respectively) and 50 (77 %) were not. In patients without NOAC, dabigatran was not detectable (0 ng/ml), and plasma levels of rivaroxaban (median: 10.0 ng/ml, IQR 7.0) and apixaban (7.2 ng/ml, IQR 6.7) were below our lower thresholds that allow thrombolysis. In patients with dabigatran pre-treatment, trough levels (58.0 ng/ml, IQR 143.0) were below our upper threshold that would allow thrombolysis in 3/5 patients. In patients receiving rivaroxaban, trough level (68.0 ng/ml, IQR 64.0) was below our predefined upper thresholds that would allow thrombolysis in 4/5 patients. In all patients on apixaban, trough level was above our predefined threshold of 40 ng/ml that precludes thrombolysis (98.2 ng/ml, IQR 84.3). Predefined thresholds of NOAC plasma levels in the decision of thrombolysis in NOAC treated AIS patients might supplement routine coagulation tests and should be validated in a larger study population.

Background: A novel multiparametric approach from the Neurosonology Research Group (NSRG) of the World Federation of Neurology has been proposed for duplex ultrasound (DUS) grading of internal carotid artery (ICA) stenosis. We aimed to determine the accuracy of CT-angiography (CTA) compared with the widely used NSRG ultrasound criteria for diagnosis of extracranial ICA stenosis. Methods: We studied consecutive acute ischemic stroke patients who were admitted to our tertiary stroke center from 01/2012 to 12/2012 and underwent CTA and DUS. On DUS, ICA stenosis and complete occlusion were graded according to the published NSRG multiparametric criteria. Axial CTA source images were independently assessed and NASCET-type measurements were manually performed for each extracranial ICA. In addition, each ICA was reviewed for complete occlusion. We calculated accuracy parameters of CTA for identification of 50-99% and 70-99% ICA stenosis, as well as complete ICA occlusion using DUS as reference. Results: A total of 339 patients (age 72±12yrs; 58% men; median NIHSS 4, interquartile range 8) provided 651 DUS and CTA measurement pairs for comparison. On DUS, 50-99% stenosis was found in 28, 70-99% stenosis in 16, and complete occlusion in 29 internal carotid arteries. The sensitivity of CTA against DUS was low for both detection of 50-99% and 70-99% ICA stenosis (64% and 31%, respectively). Further accuracy parameters of CTA were as follows: specificity 97%, PPV 49%, NPV 98% and overall accuracy 96% (18 true positive, 604 true negative, 19 false positive and 10 false negatives), and 99%, 56%, 98% and 98% (5 true positive, 631 true negative, 4 false positive and 11 false negatives), respectively. The highest accuracy of CTA was obtained for discriminating between complete ICA occlusion and non-occlusion: 100%, 96%, 91%, 100% and 99%. Conclusions: In comparison with the new and widely used NSRG criteria, CTA NASCET-type measurements seem to underestimate the degree of extracranial ICA stenosis. The validity of the NSRG criteria is currently evaluated in a prospective multicenter validation study utilizing invasive angiography as the gold standard.

Background: Telestroke networks apply specialized stroke care in rural areas. A short “onset-to-treatment-time” (OTT) reduces the risk of disability and death after thrombolysis. To minimize OTT the “door-to-needle-time” (DNT) should be less than 60 minutes. However, this is not achieved in many telestroke networks. We postulate that telestroke networks can accomplish adequate OTT′s despite of extended DNT′s. Methods: We retrospectively analyzed data of consecutive stroke patients treated with thrombolytics within the Stroke-East-Saxony-Network (SOS-NET) from 07/2007 to 07/2012. Time of symptom onset, hospital admission, CT scan, teleconsultation and thrombolysis were derived from in-patient records. DTN and OTT time were calculated. We report median values and interquartile range (IQR) as well as symptomatic intracranial hemorrhage (sICH) by ECASS-2-criteria. Results: 1659 patients of 3172 teleconsultations had an acute ischemic stroke. Thrombolysis was recommended in 688 and performed in 657 patients. Complete data were available for 368 patients (median age 77 [IQR) 12] years, NIHSS score 12 [IQR 10]). Twenty-three patients (6.3%) suffered sICH. Time from symptom onset to hospital admission was 63 minutes (IQR 47) and hospital admission to CT scan 16 minutes (IQR 15). The teleconsultation took 20 minutes (IQR 13) and time from teleconsultation to treatment was 40 minutes (IQR 22). DNT was 70 (IQR 33), OTT 143 minutes (IQR 72). Discussion: Compared to a primary stroke center DNT was longer in the SOS-NET (70 minutes [IQR 33] vs. 20 minutes [IQR 18]) which could be explained with less expertise of the affiliated hospitals and duration of teleconsultation. However, OTT was 143 minutes [IQR 72] and not different to OTT in this single center (120 [IQR 90]) or in a large regional registry (144 minutes [IQR 115-170]), respectively. This is probably because telestroke care prevents transportation of patients. Conclusion: OTT is more important in the assessment of stroke care in rural areas than DNT alone. Telestroke care can implement adequate OTT despite delayed DNT. Nevertheless, DNT still got room for improvement.

Background and Purpose: Treatment with Selective Serotonin Reuptake Inhibitors (SSRIs) following acute ischemic stroke was shown to improve functional and motor recovery independently of depression, possibly mediated by long-term mechanisms such as increased brain plasticity. In animal studies, chronic SSRI treatment is superior over short-term SSRI in evoking neurogenesis but the applicability of this observation to humans remains unelucidated. We hypothesized that pre-treatment with SSRI in acute ischemic stroke patients is associated with improved recovery compared to post-stroke SSRI. Subjects and Methods: We performed an exploratory analysis in consecutive acute ischemic stroke patients who were pre-treated or treated de novo either with fluoxetine, citalopram or escitalopram. Effects of SSRI-pre-treatment on short-term clinical (total NIHSS and NIHSS motor items) and functional (mRS) outcome at discharge compared to post-stroke SSRI were assessed using bivariate and multivariate analyses. Results: Of 2653 patients screened, 239 were included (aged 69±14 years, mean±SD; 42% men, baseline median NIHSS 7 [IQR, 10]). Compared to post-stroke SSRI (n=188), in the SSRI pre-treatment group (n=51) favorable functional outcome at discharge (mRS≤2) was more frequent (41% vs. 20%; p=0.002), duration of hospitalization was shorter (median: 7 versus 11 days; p Conclusions: Our data suggest that pre-treatment with SSRI may be linked to early clinical recovery after acute ischemic stroke and support the hypothesis that pre-stroke SSRI might be superior to post-stroke SSRI.

Background: Currently there is no standardized guidance on post-stroke management and adherence to secondary stroke prevention guidelines is modest in stroke survivors. We aimed to determine the feasibility of a self-developed evidence-based post-stroke pathway and its impact on secondary stroke prevention and long-term functional outcome. Methods: Acute ischemic stroke patients were prospectively included in a standardized poststroke pathway facilitated by a single certified case manager (CM). The one-year pathway comprised educational discussions on stroke as well as quarterly check-ups for vascular risk factors, life-style changes and adherence to antithrombotic/anticoagulant therapy. The CM intervened when deviations from stroke prevention guidelines were present and if judged necessary. At 12 months, we compared achieved target goals for secondary prevention, functional outcome, stroke recurrence and vascular death with age- and gender-matched controls that received usual post-stroke care. Results: We included 45 cases and 45 controls. At 12 months, the following target goals were more frequently achieved in patients with CM than in controls: blood pressure (100% vs. 46%, p Conclusions: Our pilot data suggest that organized post-stroke care may enhance achievement of secondary prevention goals. Its possible effect on stroke recurrence, long-term disability and quality of life is currently investigated in a prospective cohort study.

Selective serotonin reuptake inhibitors (SSRIs) administered in patients following acute ischemic stroke have shown to improve clinical recovery independently of changes in depression. Animal studies have demonstrated that sustained SSRI treatment is superior to short-term SSRI in evoking neurogenesis but how this benefit translates into humans remains to be answered. We hypothesized that in acute ischemic stroke patients, SSRI treatment started before the event leads to improved short-term outcomes compared to de novo SSRI treatment poststroke.We performed an exploratory analysis in consecutive acute ischemic stroke patients and compared patients already receiving fluoxetine, citalopram, or escitalopram with those who started treatment de novo.Of 2653 screened patients, 239 were included (age, 69 ± 14 years; 42% men, baseline median National Institutes of Health Stroke Scale score, 7 [IQR, 10]). Of these patients, 51 started treatment with SSRI before stroke and 188 were prescribed newly SSRIs during hospitalization. In the adjusted multivariate logistic regression models, SSRI pretreatment was associated with favorable functional outcome at discharge defined as a modified Rankin Scale score of 2 or less (odds ratio [OR], 4.00; 95% confidence interval [CI], 1.68-9.57; P.005), improved early clinical recovery (OR, 2.35; 95% CI, 1.15-4.81; P = .02), and a trend toward prediction of superior motor recovery (OR, 1.82; 95% CI, .90-3.68; P.01).Our data suggest that SSRI pretreatment may improve clinical outcomes in the early stages of acute ischemic stroke supporting the hypothesis that prolonged SSRI treatment started prestroke is superior to poststroke SSRI.

Background and Purpose— The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods— The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results— Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA 2 DS 2 -VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30–0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively ( P =0.003). Conclusions— Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA 2 DS 2 -VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

Kristian Barlinn,1 Jessica Kepplinger,1 Volker Puetz,1 Ben M Illigens,2 Ulf Bodechtel,1 Timo Siepmann1 1Department of Neurology, University Hospital Carl Gustav Carus Dresden, University of Technology Dresden, Dresden, Germany; 2Department ofNeurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Abstract: There is growing evidence that depression increases the risk of incident stroke. However, few studies have considered possible residual confounding effects by preexistent cerebrovascular and cardiac diseases. Therefore, we synthesized data from cohort studies to explore whether depressed individuals free of cerebrovascular and cardiac diseases are at higher risk of incident stroke. We searched the electronic databases PubMed and Medline for eligible cohort studies that examined the prospective association between depression and first-ever stroke. A random-effects model was used for quantitative data synthesis. Sensitivity analyses comprised cohort studies that considered a lag period with exclusion of incident strokes in the first years of follow-up to minimize residual confounding by preexistent silent strokes and excluded cardiac disease at baseline. Overall, we identified 28 cohort studies with 681,139 participants and 13,436 (1.97%) incident stroke cases. The pooled risk estimate revealed an increased risk of incident stroke for depression (relative risk 1.40, 95% confidence interval [CI] 1.27–1.53; P

Background The Stroke Eastern Saxony Network (SOS-NET) provides telecare for acute stroke patients. Stroke neurologists recommend intravenous thrombolysis based on clinical assessment and cerebral computed tomography (CT) evaluation using Alberta Stroke Program Early CT score (ASPECTS). We sought to assess whether ASPECTS misinterpretation by stroke neurologists was associated with thrombolysis-related symptomatic intracranial hemorrhage (sICH). Methods We retrospectively analyzed consecutive SOS-NET patients treated with thrombolytics from July 2007 to July 2012. Experienced neuroradiologists re-evaluated CT scans blinded to clinical information providing reference standard. We defined ASPECTS underestimation as ASPECTS stroke neurologist − ASPECTS neuroradiologist more than 1 point. Primary outcome was sICH by European Cooperative Acute Stroke Study II criteria. Secondary outcome was unfavorable outcome at discharge defined as modified Rankin Scale scores 3 or more. Results Of 1659 patients with acute ischemic stroke, thrombolysis was performed in 657 patients. Complete primary outcome and imaging data were available for 432 patients (median age, 75; interquartile range [IQR], 12 years; National Institutes of Health Stroke Scale score, 12 [IQR, 11]; 52.8% women). Nineteen patients (4.4%) had sICH, and 259 patients (60.0%) had an unfavorable outcome at discharge. Interobserver agreement between ASPECTS assessment was fair (κ = .51). ASPECTS underestimation was neither associated with sICH (adjusted odds ratio (OR), 1.32; 95% confidence interval (CI), .36-4.83, P = .68) nor unfavorable outcome (adjusted OR, 1.10; 95% CI, .47-2.54; P = .83). Conclusions Despite fair interrater agreement between stroke neurologists and expert neuroradiologists, underestimation of ASPECTS by the former was not associated with thrombolysis-related sICH in our telestroke network.

A 42-year-old man with no history of trauma experienced acute numbness in his right arm and leg. A pulsating left cervical tumor was noted on clinical examination. Carotid ultrasound demonstrated significant widening of the left proximal internal carotid artery (ICA) and a large nonocclusive hypoechoic structure compatible with an aneurysm and intraluminal thrombus (figure, B, D, and E). MRI confirmed a fusiform extracranial ICA aneurysm and showed a left-sided small embolic stroke (figure, A and C). The patient underwent anticoagulation with low-molecular-weight heparin and eventually surgical treatment (i.e., resection and saphenous vein graft interposition). Histopathology revealed severe atherosclerosis. Extracranial ICA aneurysms are rare and can cause embolic stroke.1 The underlying etiology is diverse, with atherosclerosis being the most common entity.2

Background Peripheral arterial disease (PAD) is common in patients with acute cerebral ischemia. Indexes of resistance derived from the systolic and diastolic velocities are routinely used in diagnostic transcranial Doppler (TCD) to detect intracranial arterial disease. We sought to explore whether these indexes can predict the presence of PAD in acute cerebral ischemia. Methods We prospectively evaluated consecutive patients with acute cerebral ischemia. On TCD, peak-systolic and end-diastolic velocities in both middle cerebral and basilar arteries were manually measured to calculate pulsatility index (PI) and resistance index (RI). Increased resistance was defined as PI equal to 1.2 or more and RI equal to .75 or more. Ankle–brachial index (ABI) measurements were performed and an ABI equal to .9 or more was considered predictive of definite PAD. Results We included 95 patients (45 male, 50 female) aged 66 ± 9 years with a median National Institutes Health Stroke Scale score of 3 (interquartile range, 8) points. The ABI was abnormal and consistent with definite PAD in 24 of 95 (25.3%; 95% confidence interval [CI], 16.4-34.2) patients. Increased PI did not differ among patients with and without PAD (20.8% vs. 28.2%, P = .60). Only 1 patient with PAD had increased RI as opposed to 4 patients without PAD (4.2% vs. 5.6%, P = 1.0). Increased PI was not found to be an independent predictor of PAD (odds ratio [OR], .68; 95% CI, .22-2.12; P = .51). Increases in both PI and RI independently predicted arterial hypertension (OR, 1.62; 95% CI, 1.19-2.21; P = .002 and OR, 3.20; 95% CI, 1.51-6.77; P = .002, respectively). Conclusions Our findings indicate that PAD cannot be inferred from intracranial flow parameters predictive of arterial disease and risk factors such as hypertension among patients with acute cerebral ischemia.

To prospectively evaluate the prognostic impact of multimodal computed tomography-based imaging in ischemic stroke patients potentially eligible for reperfusion therapy.Anterior circulation stroke patients underwent non-contrast CT (NCCT), CT-angiography, and CT-perfusion within 12 h from symptom-onset. Patients could be treated with intravenous-tissue plasminogen activator (IV-tPA), endovascular or combined reperfusion therapies. Cerebral imaging profiles (IP) were NCCT-Alberta Stroke Program Early CT Score (ASPECTS)7 (IP1); NCCT-ASPECTS5 and proximal occlusion on CT-angiography (IP2); CT-perfusion mismatch between cerebral blood volume (CBV)-ASPECTS, and cerebral blood flow (CBF)-ASPECTS ≥ 2 (IP3). Favorable outcome was defined as modified Rankin Scale ≤ 2 at 3 months.Of 102 included patients, 62 (61%) received any reperfusion therapy. In IP2 and IP3, favorable outcome was more frequent in patients with reperfusion therapy than in those without; however, this did not reach statistical significance (IP2: 39% vs 15%, p = 0.26; IP3: 50% vs 17 %; p = 0.31). No difference was seen in IP1 (58% vs 58%, p = 1.0). In IP2, patients with IV-tPA alone achieved better functional outcome (50% vs 11%, p = 0.03) and lower mortality (0% vs 28%, p = 0.045) than those without.Our results suggest a benefit with imaging profile selection based upon the combination of a small-to-moderate-sized infarction and a visible intracranial occlusion in patients receiving IV-tPA. Reperfusion therapy may be futile in patients without proven vessel occlusion.

Background: We developed a standardized pathway for post-stroke care facilitated through a case manager (CM) to ensure minimization of risk factors, life-style changes and continuation of secondary prevention medication. Methods: Consecutive acute stroke patients were prospectively assigned to a certified CM. The 1-year post-stroke care pathway comprised initial educational discussion, personal patients’ home visits and quarterly telephone contacts. Further personal contacts were conducted when judged necessary. Target values for vascular risk factors were pre-defined according to current stroke guidelines, compared with regular check-ups and intervened when necessary. A closing meeting including assessment of stroke recurrence was performed. Results: Between 12/2011 and 07/2013 we enrolled 74 of 111 screened patients: 57% male, mean age 71+/-14 yrs, median NIHSS 2 (range 0-16), 76% ischemic, 4% hemorrhagic stroke and 20% TIA. Of 74 patients, 10 refused follow-up care. Overall, 356 home visits (4.8/patient) and 1233 phone contacts (16.7/patient) were conducted. One hundred-eighty seven specific interventions were necessary mostly due to missing medication, non-compliance and social needs. Achieved vascular risk factor goals are presented in the Table. No recurrent stroke occurred. Among screened patients who refused CM, stroke recurrence rate was 22% after 12 months. Conclusion: The preliminary data of our pilot project suggest that case management is capable of achieving predefined goals for secondary prevention. To investigate its impact on stroke recurrence risk and prevention of long-term care dependency, we initiate a randomized controlled trial.

Variability in responsiveness to clopidogrel is a clinical problem in secondary prevention after cerebral ischaemia which has been suggested to be linked to competitive metabolization of clopidogrel and cytochrome P450 (CYP) 3A4-oxidated statins such as simvastatin. We assessed the hypothesis that simvastatin, in contrast to CYP 2C9-metabolized fluvastatin, reduces clopidogrel-mediated platelet inhibition.We performed a randomized, double-blind, double-dummy, two period crossover study in 13 patients with cerebral ischaemia (8F, 5 M), aged 64.1 ± 8.0 years (mean ± SD). After a 14 day period in which all patients received 75 mg clopidogrel day(-1) , patients additionally received either 20 mg simvastatin day(-1) or 80 mg fluvastatin day(-1) for 14 days. Regimens were crossed over after a 14 day wash-out period and switched regimens were continued for another 14 days. Platelet aggregation, clopidogrel active metabolite (CAM) plasma concentrations and routine laboratory parameters including prothrombin time (PT) Quick percent value were assessed at baseline and following each treatment phase.Clopidogrel reduced platelet aggregation in all patients as expected. Platelet aggregation and CAM plasma concentrations were unaltered when simvastatin or fluvastatin was added to clopidogrel. Simvastatin decreased PT Quick percent value (decrease from 109 ± 10.5% to 103 ± 11%, P0.05) when combined with clopidogrel but there was no such change following treatment with fluvastatin and clopidogrel.Our data indicate that treatment with CYP 3A4-metabolized simvastatin does not jeopardize clopidogrel-mediated inhibition of platelet aggregation. After co-administration of simvastatin and clopidogrel we observed a decrease in the PT Quick percent value which could be due to simvastatin-induced reduction of activity of prothrombin fragment 1 + 2.

Background: Peripheral arterial disease (PAD) is common in patients with acute cerebral ischemia, yet little testing, if any, is done during in-hospital stay. The pulsatility index (PI) from the systolic and diastolic velocity measurements on TCD is routinely used in stroke patients to assess resistance to flow and thereby intracranial atheromatous disease. We sought to explore whether the PI can indirectly predict the presence of PAD in these patients. Methods: We prospectively evaluated consecutive patients with acute cerebral ischemia by TCD and ankle-brachial-index (ABI) measurements. Clinical variables were collected at baseline. On TCD, peak systolic, end-diastolic and mean flow velocities in both middle cerebral and basilar arteries were manually measured. According to a complete four-cardiac cycle sweep without arrhythmias, PI was automatically calculated for each of the 3 arteries and the average was used for analysis. Bilateral brachial, tibial and pedal systolic blood pressures were measured using a 4-MHz continuous-wave Doppler (average over two measurements). ABI 0.91 to 0.99 was considered as borderline, ABI Results: We enrolled a total of 53 patients: 68% ischemic stroke, 32% TIA, 60% Caucasians, 42% male, mean age 64±10 yrs, median NIHSS 4 (range 0-20). ABI was borderline or abnormal in 26/53 (49%) including 12/53 (23%) patients with ABIs consistent with PAD. Baseline characteristics were similar between patients with and without PAD. The mean PI did not differ among patients with and without PAD (0.92±0.08 vs. 1.01±0.04, p=0.24). The PI was not found to be an independent predictor of PAD (OR=0.21, 95% CI 0.01-3.64, p=0.285). Similarly, the PI did not predict ABI (p=0.96). PI strongly predicted history of arterial hypertension (OR=530.04, 95%CI 5.18-54215.57, p=0.008). Conclusions: Our findings do not suggest that the presence of PAD can be inferred from intracranial flow parameters predictive of atheromatous disease and risk factors such as hypertension among patients with acute cerebral ischemia. However, the high frequency of PAD in these patients warrants further investigation to facilitate routine and early detection of this disease.

Background: The Stroke Eastern Saxony Network (SOS-NET) provides telemedical consultations for patients with acute ischemic stroke. Stroke neurologists recommend intravenous (IV) thrombolysis based on cerebral CT scan evaluation with the Alberta Stroke Program Early CT score (ASPECTS). We sought to assess whether: 1) underestimation of early ischemic changes (EIC) was associated with symptomatic intracranial hemorrhage (sICH); 2) whether high ASPECTS predicted favorable outcome after telethrombolysis. Methods: We retrospectively analyzed prospectively collected data of SOS-NET patients who received IV telethrombolysis from 10/08 to 07/12. Two experienced neuroradiologists re-evaluated cerebral CT scans blinded to clinical findings providing reference standard. We defined underestimation of EIC by stroke neurologists as ASPECTS deviations > +1 point and favorable outcome as modified Rankin scale (mRs) scores of 0 to 2 at discharge. We analyzed whether underestimation of EIC was associated with sICH by ECASS-2 criteria and whether ASPECTS dichotomized at 8-10 versus 0-7 was associated with favorable outcome. Results: Of 647 patients who received IV telethrombolysis during the study term, clinical and imaging data were available for 344 patients (median age 76 [IQR 70 - 81] years, NIHSS score 11.5 [IQR 6 - 18], 54.8% female, onset-to-treatment-time 143 minutes [IQR 110 - 190]). At discharge, 91 patients (27.2%) had a favorable outcome. Overall 14 patients (4.2%) suffered thrombolysis-related sICH. Compared to reference, stroke neurologists underestimated EIC extent in 30 patients (9%). ASPECTS deviations were not associated with thrombolysis-related sICH (3.3% vs. 4.3%; p=1.0). Patients with higher ASPECTS (n=299) were more likely to have a favorable outcome than patients with low ASPECTS (n=35) (35.3% vs. 10.3%; p=0.006). Conclusion: Underestimation of EIC by stroke neurologists was rare and not associated with thrombolysis-related sICH in our telestroke network. ASPECTS of 8 - 10 on pretreatment CT is associated with favorable clinical outcome following telethrombolysis.

Background: Acute ischemic stroke (AIS) patients receiving novel oral anticoagulants (NOAC) are commonly excluded from thrombolytic therapy as reliable bedside tests for anticoagulation monitoring are lacking. We aimed to prospectively investigate the applicability of our institutional protocol for the management of AIS patients on NOAC that is based on expert recommendations Methods: We studied consecutive AIS patients not receiving NOAC and hospitalized general patients receiving NOAC. We performed standard coagulation tests including INR, activated partial thromboplastin time (aPTT), thrombin time (TT) and trough level tests for dabigatran, rivaroxaban and apixaban. In AIS patients, blood samples were taken immediately after admission. Results: We enrolled 40 patients: mean age 73±15 yrs, 30% male, median NIHSS 3 (range 0-17), 62.5% AIS. Fifteen patients received NOAC (i.e., 5 dabigatran, 5 rivaroxaban, 5 apixaban). In AIS patients not receiving NOAC, coagulation parameters were within normal limits (INR 0.99±0.07, aPTT 27.4±2.6, TT 16.7±1.2) and significantly lower than in those on dabigatran (INR 1.28±0.15, aPTT 39.6±7.4, TT 111.9±40.8; p Conclusions: In AIS patients potentially amenable to thrombolytic therapy, altered routine coagulation tests may point to an intake of NOAC. Predefined values for dabigatran, rivaroxaban and apixaban need to be adjusted in a larger validation study and individually validated by local laboratories to be prepared for emergency situations.

BACKGROUND: In secondary prevention after ischemic stroke variability in individual responsiveness to clopidogrel is a clinically relevant problem. Among possible mechanisms that may contribute to this phenomenon, clopidogrel-statin interactions are discussed. Particularly, competitive metabolization of lipohilic statins (i.e. simvastatin) and clopidogrel by cytochrome P450 (CYP) 3A4 was suggested to reduce the inhibitory effect of clopidogrel on platelet aggregation. In contrast, hydrophilic fluvastatin is predominantly metabolized by CYP 2C9 and is therefore assumed not to alter clopidogrel efficacy. We assessed the hypothesis that simvastatin, in contrast to fluvastatin, reduces clopidogrel-mediated platelet inhibition. METHODS: We performed a randomized double blind placebo controlled crossover study in 13 patients with acute ischemic stroke. After an initial 13 day period in which all patients received 75 mg clopidogrel/day, one group (n=6) was randomized to additionally receive 20 mg simvastatin/day and placebo for 13 days. During this period the other group (n=7) received 80 mg fluvastatin and placebo in addition to clopidogrel. Regimens were crossed over after a 13 day wash-out period during which patients received clopidogrel only. Switched regimens were then continued for another 13 days. Assessment of ADP-induced platelet aggregation, plasma levels of clopidogrel active metabolite and coagulation was performed at baseline, at each regimen change and at study completion. RESULTS: We studied 7 female and 6 male patients, ages 63.9±3 years (mean±SD). Plasma levels of clopidogrel active metabolite and platelet aggregation were unaltered when simvastatin or fluvastatin were added to treatment with clopidogrel. Simvastatin decreased prothrombin ratio (decrease from 109±10,5% to 103±11%, p CONCLUSIONS: This study indicates that neither fluvastatin nor simvastatin alter clopidogrel-mediated platelet inhibition. In co-administration of simvastatin and clopidogrel we observed decrease in prothrombin ratio which could be due to simvastatin-induced reduction of prothrombin fragment 1 and 2 activity.

The aim of this study was to determine the importance of sleep apnea in relation to clinically silent microvascular brain tissue changes in patients with acute cerebral ischemia. Patients with acute cerebral ischemia prospectively underwent nocturnal respiratory polygraphy within 5 days from symptom-onset. Sleep apnea was defined as apnea–hypopnea-index (AHI) ≥5/h. Experienced readers blinded to clinical and sleep-related data reviewed brain computed tomography and magnetic resonance imaging scans for leukoaraiosis and chronic lacunar infarctions. Ischemic lesions were considered clinically silent when patients did not recall associated stroke-like symptoms. Functional outcome was assessed with modified Rankin Scale at discharge, 6 and 12 months. Fifty-one of 56 (91 %) patients had sleep apnea of any degree. Patients with moderate-to-severe leukoaraiosis (Wahlund score ≥5) were found to have higher mean AHI than those with none or mild leukoaraiosis (34.4 vs. 12.8/h, p

BackgroundTelemedicine may facilitate the selection of stroke patients who require emergency transfer to a comprehensive stroke center to receive additional therapies other than intravenous tissue plasminogen activator.Aims and/or hypothesisWe sought to analyze frequency, patient characteristics, and specific therapies among emergently transferred patients within the telemedical Stroke East Saxony Network.MethodsWe reviewed consecutive patients who were transferred emergently from remote spoke sites to hub sites. Certified stroke neurologists performed teleconsultations 24/7, with access to high-speed videoconferencing and transfer of brain images. Emergent transfers were initiated when considered necessary by the stroke neurologist.ResultsIn 2009 and 2010, we conducted 1413 teleconsultations and subsequently recommended transfer in 339 (24%) patients [mean age 64 ± 14 years, 54% males, median National Institutes of Health Stroke Scale score 5 (interquartile range, IQR 12). The mean teleconsultation-to-arrival time was 1·7 ± 0·8 h (median 1·6 h). Sixty-eight (20%) transferred patients had a nonstroke diagnosis. The remaining 271 (80%) patients had stroke diagnoses [ischemic stroke, 114 (34%); transient ischemic attack, 8 (2%); and intracranial haemorrhage, 149 (44%)]. Forty (35%) ischemic stroke patients received tissue plasminogen activator at spoke sites (‘drip and ship’). Of the 240 stroke patients emergently transferred to the main hub site, 119 (49·6%) received at least one specific stroke therapy.ConclusionA remarkable number of stroke patients can be transferred within a telemedical network to enable the delivery of specific stroke therapies that require advanced multispecialty expertise. Whether associated logistic efforts and costs have an impact on patients' clinical outcomes needs to be evaluated.

Objective: To determine the reliability and therapeutic impact of standardized cerebral CT evaluation and quantification of early ischemic changes (EIC) with the Alberta Stroke Program Early CT Score (ASPECTS) by stroke neurologists in the Stroke Eastern Saxony Network (SOS-NET), which provides telemedical consultations for patients with acute ischemic stroke. Methods: Two neuroradiologists re-evaluated all CT scans of consecutive SOS-NET patients in 2009 blinded to clinical information providing reference standard. We defined discrepant CT findings as all false-positive or false-negative EIC and brain pathology findings and ASPECTS deviations >1 point. We subsequently discussed the clinical impact of discrepant CT findings unblinded to clinical information. Weighted kappa (κ w ) statistic was used to determine the interobserver agreement for ASPECTS. Results: Of 582 patients, complete imaging data were available for 536 patients (351 cerebral ischemic events, 105 primary intracranial hemorrhages, and 80 stroke mimics). The neuroradiologists detected discrepant CT findings in 43 patients (8.0%) that were rated as clinically relevant in 9 patients (1.7%). Stroke neurologists recommended IV thrombolysis in 8 patients despite extensive EIC (ASPECTS ≤5). One of these patients had symptomatic intracranial hemorrhage. In 1 nonthrombolyzed patient, the stroke neurologist missed subdural hematoma. The interobserver agreement on ASPECTS between stroke neurologists and expert readers was substantial (κ w = 0.62; 95% confidence interval 0.54–0.71). Conclusions: Clinically relevant misinterpretation of the CT scans was rare in our acute telestroke service. ASPECTS is a reliable tool to assess the extent of EIC by stroke neurologists in telemedicine in real time.

Background&Purpose: Sleep apnea (SA) is an increasingly recognized stroke risk factor. Little is known about the relationship between SA and sleep-related ischemic stroke (SIS). As part of our prospective study of early in-hospital overnight sleep studies in stroke patients, we aimed to evaluate the proportion and severity of SA in patients with SIS. Subjects&Methods: We prospectively (11/2009-05/2011) performed overnight sleep studies in consecutive patients with acute cerebral ischemia without known SA during their hospital stay ( Results: Of 61 patients who met the inclusion criteria, 56 had analyzable sleep studies (18% TIA; 54% women; mean age 64±8 years; mean BMI 27.2±3.9; median baseline NIHSS score 1 point, range 0-15; median Epworth Sleepiness Scale score 5 points, range 0-13; mean AHI 23.6±19.3/h). SIS was found in 19 (34%) patients including 14 (25%) WUS. Nearly 91% (51/56) had SA; 32% (18/56) mild, 30% (17/56) moderate, and 29% (16/56) severe. There were no significant differences in baseline characteristics between SIS and non-SIS patients except for gender (males 26% vs. 57%, p=.03) and atrial fibrillation (32% vs. 5%, p=.008). Functional outcome at discharge (p=.24) and 6 months (p=.35) did not differ between SIS and non-SIS patients. When comparing SIS and non-SIS patients, no differences were found regarding the presence (95% vs. 89%, p=.49) or severity (e.g., severe SA: 32% vs. 27%, p=.69) of SA. Similarly, there were no differences in the presence (100% vs. 88%, p=.17) or severity (e.g., severe SA: 32% vs. 29%, p=.66) of SA when comparing WUS and non-WUS patients. AHI did not prove to be a significant independent predictor of SIS (p=.45) or WUS (p=.56). Conclusions: The similar proportions and severity of SA in our patients with sleep-related and non-sleep-related ischemic strokes may be due to the overall high prevalence of SA (91%) in the entire study population, which highlights the importance of early screening for SA in all ischemic stroke patients. As the majority of our patients had mild strokes, these findings warrant further investigation in a moderate-to-severe stroke population.

Background: In the recently stopped SAMMPRIS trial, enrolled patients had to be stable for at least 3 days since the index event. Following that, the early results suggest a benefit with aggressive medical therapy and risk factor modification. We sought to explore the frequency, risk of early neuroworsening (NW), stroke recurrence and short-term prognosis in patients with symptomatic intracranial atherosclerotic disease (IAD). Methods: We retrospectively reviewed our consecutive stroke database for patients with acute cerebral ischemia admitted in 2010 to our tertiary hospital. Demographics, vascular risk factors, clinical and imaging data were collected. The extent of IAD (mild 2 points) without any systemic cause. Functional outcome (mRS), stroke recurrence rate and death were also determined at discharge and follow-up. Results: A total of 438 patients with acute cerebral ischemia were reviewed (18% TIA; median age 65, range 21-99; 51% men, 61% Caucasians; median NIHSS 5, range 0-40), of which 408 (93%) had vascular imaging. IAD was present in 98/408 (24%) patients with 40 (9.8%) symptomatic 50-99% IAD. Baseline characteristics, clinical data and outcomes are summarized in the Table . The median follow-up time was 31 (0-507) days. After adjusting for known confounders, neither moderate nor severe IAD alone predicted early NW, functional outcome, stroke recurrence or death (at discharge or follow-up). However, when the 15 cases of 50-69% were combined with the 25 cases of 70-99% IAD (50-99%), symptomatic IAD was a significant independent predictor of early NW (OR 4.2, 95%CI 1.2-14.8, p=0.025), but not of stroke recurrence, outcome or death (at discharge or follow-up). In addition, NW had a strong positive correlation to poor modified Rankin and death (at discharge and follow-up, p Conclusions: Symptomatic 50-99% IAD is common in our patient population and it predicts early neuroworsening. The strong correlation between neuroworsening and poor functional outcome and death underscores the importance of prompt diagnostic work-up for IAD. Despite the initial results of SAMMPRIS it is unclear if stenting has no role in acute and subacute management of these patients. This could be a subject of a randomized controlled trial.

Background&Purpose: Although sickle cell disease (SCD) is strongly linked to stroke across all haplotypes in the pediatric population, Iranian children with Saudi-Asian haplotype are less affected by this complication. TCD is known to identify the highest risk group in African-Americans who need to receive and stay on blood transfusions, but it is unclear if the same flow velocity cut-offs can be applied to the Iranian population. We therefore aimed first to evaluate baseline TCD findings in Iranian children with SCD and no prior strokes. Subjects&Methods: Children with genetically confirmed SCD (Arabian haplotype, homozygote) and without SCD (controls) aged 3 to 16 years were prospectively recruited from pediatric outpatient clinic over a period of 9 months. All children had no previous stroke or any neurologic deficit. No transfusion was given within one month prior to TCD examination and patients were not on any medication that may affect cerebral hemodynamics. We performed TCD examinations in both groups to determine flow velocities in the middle cerebral (MCA) and terminal internal carotid arteries (TICA). Mann-Whitney U test was used to compare TCD variables between the two groups. Results: Of 74 screened children, 60 met the inclusion/exclusion criteria (62% female; mean age 10±4 years). Baseline characteristics did not differ between the cases and controls, except hemoglobin (Hb) which was significantly lower in the SCD group (mean 8.83±1.43 g/dL vs. 10.3±1.03 g/dL, p170 cm/s MFV. Conclusions: Among Iranian children with asymptomatic SCD and without receiving recent transfusion TCD velocities could be much lower than those observed in STOP studies, and some of the high risk group may be identified with velocities lower than 170 cm/s. A prospective validation of ethnicity-specific diagnostic criteria is warranted.

Background&Purpose: Although clinically silent infarcts (CSI) have been linked to an increased risk of stroke, only limited data exist regarding associated risk factors. Sleep apnea (SA), as an independent stroke risk factor itself, is associated with chronic microvascular changes (CMC), yet the relationship between SA and CSI remains unclear. We sought to determine the frequency and severity of SA in patients with CSI or CMC as well as how SA relates to outcomes in these patients. Subjects&Methods: Over an 18-month period, consecutive patients with acute cerebral ischemia prospectively underwent overnight in-hospital respiratory polygraphy within 5 days from symptom-onset. Sleep apnea was present when apnea-hypopnea-index (AHI) was ≥5/h. We collected demographics and clinical variables at baseline. All CTs and MRIs were independently reviewed by a neuroradiologist who was blinded to the sleep study findings and outcome. CSI was defined as any lesion consistent with a remote ischemic infarct without known history of a corresponding neurologic deficit. CMC was defined as diffuse white matter alterations not attributable to another neurologic condition. Modified Rankin Scale (mRS) was used to assess functional outcome at discharge and 180 days. Baseline demographics were analyzed using chi-square and Wilcoxon rank sum test. Correlations and logistic regression were used to predict CSI and CMC. Results: We evaluated a total of 56 patients for the presence of SA. Demographics, clinical variables and outcomes are shown in the Table . SA was present in 91% (n=51) of the study population. There was no correlation between AHI and the presence of CMC (p=0.75). After adjustment for gender, AHI was found to be a significant independent predictor of CSI (OR 1.04, 95%CI 1.0-1.08; p=0.03). In patients who had either CSI or CMC, the higher the AHI the less likely favorable functional outcome (mRS 0-2) was achieved at discharge (OR=0.94, 95%CI 0.89-0.99; p=0.02). AHI was not a significant independent predictor of functional outcome at 180 days (p=0.25). Conclusions: In our study population, SA was found to be frequent in both CMC and CSI with >1/3 of CMC patients and >1/2 of CSI patients having severe SA. Moreover, SA was found to be an independent predictor of clinically silent infarcts. The less favorable outcome in CSI and CMC patients with high AHI warrants further investigation in these at-risk populations, perhaps with early non-invasive ventilatory correction of sleep apnea.

Background and Purpose— The beneficial effect of intravenous thrombolytic therapy in patients with acute ischemic stroke attributable to internal carotid artery (ICA) occlusion remains unclear. The aim of this study was to evaluate the efficacy and safety of intravenous recombinant tissue-type plasminogen activator in these patients. Methods— ICARO was a case-control multicenter study on prospectively collected data. Patients with acute ischemic stroke and ICA occlusion treated with intravenous recombinant tissue-type plasminogen activator within 4.5 hours from symptom onset (cases) were compared to matched patients with acute stroke and ICA occlusion not treated with recombinant tissue-type plasminogen activator (controls). Cases and controls were matched for age, gender, and stroke severity. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale, dichotomized as favorable (score of 0–2) or unfavorable (score of 3–6). Safety outcomes were death and any intracranial bleeding. Results— Included in the analysis were 253 cases and 253 controls. Seventy-three cases (28.9%) had a favorable outcome as compared with 52 controls (20.6%; adjusted odds ratio (OR), 1.80; 95% confidence interval [CI], 1.03–3.15; P =0.037). A total of 104 patients died, 65 cases (25.7%) and 39 controls (15.4%; adjusted OR, 2.28; 95% CI, 1.36–3.22; P =0.001). There were more fatal bleedings (2.8% versus 0.4%; OR, 7.17; 95% CI, 0.87–58.71; P =0.068) in the cases than in the controls. Conclusions— In patients with stroke attributable to ICA occlusion, thrombolytic therapy results in a significant reduction in the proportion of patients dependent in activities of daily living. Increases in death and any intracranial bleeding were the trade-offs for this clinical benefit.