Search

Background: The “1-3-6-12-day rule” for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. Methods: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0–7), moderate (8–15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. Results: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)—initiating DOACS within 1, 2, 3, and 4 days, respectively—than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27–0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27–0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. Conclusions: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation.

Introduction: Pilot data suggests that organized post-stroke care enhances achievement of secondary prevention goals in stroke patients. We aimed to further investigate whether organized post-stroke care favourably affects stroke recurrence and survival. Methods: Prospective, quasi-experimental study of consecutive stroke patients admitted at two tertiary stroke centers in Saxony, Germany. According to health insurance provider status, patients were non-randomly assigned to either 12-months post-stroke pathway plus conventional care or conventional care alone. The organized post-stroke care pathway was facilitated by certified case managers and included pre-scheduled home- and phone visits aiming at educational intervention and achievement of guideline-based secondary prevention treatment goals. Primary outcomes were stroke recurrence and vascular death at 12-months. Further outcomes included favourable functional outcome (i.e. mRS 0-1), health-related quality of life and vascular risk factor control at 12-months. Results: In total, 1109 patients were recruited between 11/2011 and 12/2020. Of these, 1009 patients (91%) were assigned to organized post-stroke care and 100 (9%) to conventional care (mean age 70.6±12.8 years, 54% male, median NIHSS 3 [IQR, 1-5] points, 77.5% AIS, 17.9% TIA and 4.6% ICH). Baseline demographics and clinical characteristics were well balanced between both groups (p≥0.05). At 12-months, recurrent stroke rate was lower in the post-stroke care than in the conventional care group (5.5% vs. 14%; aOR 0.35, 95%CI 0.18-0.66; p=0.001). This association was not modified by stroke severity (TIA/minor stroke versus major stroke). Vascular death occurred in 0.2% in the post-stroke care and 3% in the conventional care group (aOR 0.07, 95%CI 0.01-0.41; p=0.003). Organized post-stroke care more frequently yielded individual treatment goals for hypertension, lipids, HbA1c, body-mass-index and secondary prevention adherence than conventional care (p Conclusions: Our results substantiate the effectiveness of case management-based post-stroke care in unselected stroke patients.

Introduction: Recent meta-analytic evidence supported efficacy and safety of bridging intravenous thrombolysis (IVT) prior to endovascular therapy (EVT) for large vessel occlusion (LVO) but large confirmatory trials are still lacking and optimal candidates for treatment have been a topic of contention lately. Objectives: We aimed to determine a cut-off in treatment times that allows identification of those who would benefit most from bridging IVT. Methods: We analyzed prospectively collected data from consecutive LVO patients who underwent EVT at a tertiary stroke center in Germany from 01/2017 to 12/2021. Patients underwent detailed cardiovascular phenotyping, repeated cranial imaging, and received standardized multidisciplinary stroke unit care. Functional outcome was assessed via modified Rankin scale three months after discharge. Ordinary ridge regression models were built to assess the impact of treatment time cut-offs on functional outcome with adjustment for age, sex, cardiovascular risk factors, baseline NIHSS, cerebrovascular territory, ASPECT score, stroke etiology and carotid artery stenting. Results: Out of 935 patients who had undergone EVT, 170 received bridging IVT (median age 74 [63-82, IQR], 52.4% females), fulfilled our criteria and were included in our analysis. Overall, onset-to-recanalization time but not onset-to-needle time was associated with functional outcome (β1=0.36, 95%CI [0.14,0.58], p=0.001 vs. p=ns). However, those who received EVT with a time delay longer than 190 minutes additionally displayed an association of onset-to-needle time and functional outcome (β1=0.64, 95%CI [0.25,1.04], p=0.02 vs. β2= 2.96, 95%CI [1.32,4.60], p=0.016). Conclusions: Our data indicates that the beneficial effect of swift bridging IVT on functional outcome is most pronounced in cases where initiation of subsequent EVT is substantially delayed.

Background and Purpose: This study aims to assess the number of patients with acute ischemic cerebrovascular events seeking in-patient medical emergency care since the implementation of social distancing measures in the coronavirus disease 2019 (COVID-19) pandemic. Methods: In this retrospective multicenter study, data on the number of hospital admissions due to acute ischemic stroke or transient ischemic attack and numbers of reperfusion therapies performed in weeks 1 to 15 of 2020 and 2019 were collected in 4 German academic stroke centers. Poisson regression was used to test for a change in admission rates before and after the implementation of extensive social distancing measures in week 12 of 2020. The analysis of anonymized regional mobility data allowed for correlations between changes in public mobility as measured by the number and length of trips taken and hospital admission for stroke/transient ischemic attack. Results: Only little variation of admission rates was observed before and after week 11 in 2019 and between the weeks 1 and 11 of 2019 and 2020. However, reflecting the impact of the COVID-19 pandemic, a significant decrease in the number of admissions for transient ischemic attack was observed (−85%, −46%, −42%) in 3 of 4 centers, while in 2 of 4 centers, stroke admission rates decreased significantly by 40% and 46% after week 12 in 2020. A relevant effect on reperfusion therapies was found for 1 center only (thrombolysis, −60%; thrombectomy, −61%). Positive correlations between number of ischemic events and mobility measures in the corresponding cities were identified for 3 of 4 centers. Conclusions: These data demonstrate and quantify decreasing hospital admissions due to ischemic cerebrovascular events and suggest that this may be a consequence of social distancing measures, in particular because hospital resources for acute stroke care were not limited during this period. Hence, raising public awareness is necessary to avoid serious healthcare and economic consequences of undiagnosed and untreated strokes and transient ischemic attacks.

Introduction: Stroke accounts for 4% of patients with acute vertigo, which is missed in up to one third of cases. Hypothesis: We hypothesized that detection of stroke underlying acute vertigo using HINTS plus (head-impulse test, nystagmus type, test of skew, hearing loss) can be improved by videooculography for automated analysis of head-impulse test (V-HIT). Materials and Methods: We evaluated patients with acute vestibular syndrome (AVS) presenting to the emergency room using HINTS plus and V-HIT-assisted HINTS plus in a randomized sequence. In addition, patients underwent cranial MRI and caloric testing. Image-confirmed posterior circulation stroke or vertebrobasilar TIA were defined as reference standard to calculate accuracy of applied vertigo assessment protocols. After study completion, we repeated statistical analysis for a third protocol that was composed post hoc by replacing the results of head-impulse test with those derived from caloric testing in the HINTS plus protocol. Results: We included 30 AVS patients (ages 55.4 ± 17.2 years, 14 females). Of these, 11 (36.7%) had MRI-confirmed posterior circulation ischemic stroke (n=4) or vertebrobasilar TIA (n=7). Conducting V-HIT-assisted HINTS plus as part of the emergency work up was feasible and displayed a tendency toward higher accuracy than conventional HINTS plus (sensitivity: 81.8%, 95%CI 48.2-97.7%; specificity 31.6%, 95%CI 12.6-56.6% vs. sensitivity 72.7%, 95%CI 39.0-94.0%; specificity 36.8%, 95%CI 16.3-61.6%). (Figure) The new caloric-supported algorithm displayed high accuracy (sensitivity 100%, 95%CI 66.4%-100%; specificity 66.7%, 95%CI 41%-86.7%). Conclusions: Our study provides pilot data on the capacity of videooculography to improve accuracy of acute vertigo assessment using HINTS plus and indicates potential value of acute caloric testing as integrative part of standardized AVS emergency work up.

Background and Purpose— Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods— We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results— Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients ( P =0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4–3.7; P P =0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2–4.9; P =0.01) end points separately. Conclusions— Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.

Introduction: To explore kidney safety profile of osmotic diuretic mannitol in patients with malignant middle cerebral artery (MCA) infarction. Methods: We analyzed data from consecutive patients with malignant MCA infarction (01/2008-12/2017). Malignant MCA infarction was defined according to clinical and radiographic DESTINY criteria. Clinical and laboratory variables were collected for all patients. We compared clinical endpoints including acute kidney failure (AKF; according to Kidney Disease: Improving Global Outcomes [KDIGO] definition) and hemodialysis between patients who received mannitol and those who did not. Multivariable model was built to explore predictor variables of AKF, in-hospital death and functional outcome at discharge. Results: Overall, 228 patients with malignant MCA infarction were analyzed: median age 67 years (IQR, 56-76), 58% men, median NIHSS 23 (17-32) points. Decompressive craniectomy was performed in 103/228 (45.2%) patients. Mannitol was administered in 100/228 (43.9%) patients over an average of 85 (30.3-139.3) hours. Average dosage was 700 (250-1050) g. Patients treated with mannitol more frequently suffered from AKF (40% vs. 7.9%; p0.05). Conclusions: Acute kidney failure appears to be a frequent complication of osmotic diuretic mannitol in patients with malignant MCA infarction. Given the lack of evidence supporting effectiveness of mannitol in these patients, its use should be carefully considered.

Introduction: Recent studies linked coronavirus disease 2019 (COVID-19) to thromboembolic complications likely mediated by increased blood coagulability and inflammatory endothelial impairment. Objective: We aimed to assess the risk of acute stroke in patients with COVID-19 related to clinical severity of the disease. Methods: We conducted an observational multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory-confirmed COVID-19 who experienced acute stroke during hospitalization. Furthermore, we performed a systematic review using PubMed/MEDLINE, EMBASE, Cochrane Library and bibliographies of identified articles following PRISMA guidelines including data from observational studies of acute stroke in COVID-19 patients. Data was extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RR) and 95% confidence intervals (95%CIs) for acute stroke related to COVID-19 severity using random effects model. Between-study heterogeneity was assessed using Cochran’s Q and I 2 -statistics. PROSPERO identifier : CRD42020187194. Results: Of 165 patients hospitalized for COVID-19 (49.1% males, median age 67 [57-79], 72.1% severe or critical) included in the multicenter study, overall stroke rate was 4.2% (95%CI: 1.9-8.7). Systematic literature search identified two observational studies involving 576 patients that were eligible for meta-analysis. Among 741 pooled COVID-19 patients overall stroke rate was 2.9% (95%CI: 1.9-4.5). Risk of acute stroke was increased for patients with severe compared to non-severe COVID-19 (RR 4.12, 95%CI 1.7-10.25; p=0.002) with no evidence of heterogeneity (I 2 =0%, p=0.82). Conclusions: Synthesized analysis of data from our multicenter study and previously published cohorts demonstrate that severity of COVID-19 is associated with an increased risk of acute stroke, underscoring the necessity of neurological monitoring in patients infected with SARS-CoV-2.

Introduction: Hypothermia may be neuroprotective in acute ischemic stroke. Stroke patients with anterior circulation large vessel occlusion (acLVO) who receive endovascular therapy (EVT) are frequently hypothermic after the procedure. We sought to analyze whether this unintended hypothermia was associated with improved functional outcome. Methods: We extracted data of consecutive patients (01/2016-04/2019) from our prospective EVT database that includes all patients screened for EVT at our center. We included patients with acLVO who received EVT and analyzed recanalization (mTICI 2b-3) and complications (i.e., pneumonia, bradyarrhythmia, venous thromboembolism) during the hospital course. We assessed functional outcome at 3 months and analyzed risk ratios (RR) for good outcome (mRS scores 0-2) and mortality of patients who were hypothermic (> 36°C) after EVT. We compared the frequency of complications and calculated RRs for good outcome and mortality in the subgroup with recanalization. Results: Among 674 patients with anterior circulation ischemic stroke, 372 patients received EVT for acLVO (178 [47%] male, age 77 years [65-82], NIHSS score 16 [12 - 20]). Of these, 186 patients (50%) were hypothermic (median [IQR] temperature 35.2°C [34.7-35.6]) and 186 patients were normothermic (media temperature 36.4 [36.2-36.8]) after EVT. At 3 months, 54 of 186 (29.0%) hypothermic patients compared with 65 of 186 (35.0%) normothermic patients had a good outcome (RR, 0.83; 95%CI 0.62-1.12) and 52 of 186 (27.9%) hypothermic patients compared with 46 of 186 (24.7%) normothermic patients had died (RR, 1.13; 95%CI 0.8-1.59). This relation was consistent in 307 patients (82.5% of all EVTs) with successful recanalization (good outcome: RR, 0.85; 95%CI 0.63-1.14.; mortality: RR, 1.05; 95%CI 0.7-1.57). More hypothermic patients suffered pneumonia (37.8% vs. 24.7%; p=0.003) or bradyarrhythmia (55.6% vs. 18.3%; p Conclusion: Unintended hypothermia following EVT for acLVO was not associated with improved functional outcome or reduced mortality but an increased complication rate in patients with acute ischemic stroke.

Introduction: In patients with acute ischaemic stroke (AIS) dysregulation of cardiac function with decreased heart rate variability (HRV) due to impaired integrity of the autonomic nervous system is a frequent complication which is associated with increased mortality and worsening of clinical outcome. HRV biofeedback has previously been suggested to improve cardiac autonomic function by increasing parasympathetic tone. Hypothesis: We hypothesized that HRV biofeedback can be used to complement stroke unit care and alleviate autonomic cardiac dysfunction following AIS. Methods: We randomly allocated patients with AIS to either receive 9 sessions of HRV (n=24) or sham (n=24) biofeedback in addition to standard stroke unit care. These patients underwent detailed assessment of autonomic cardiac function including analysis of HRV via standard deviation of NN intervals (SDNN) and spectral analysis. Furthermore, we assessed vasomotor and sudomotor autonomic function, severity of autonomic symptoms and neurological and functional outcomes. Results: We included 48 patients (19 females, ages 65±14 years, baseline NIHSS 2.2 ± 2.2, mean ± standard deviation). Patients who had undergone HRV biofeedback displayed improved cardiac function compared to baseline (SDNN 72.6 ± 52.4 ms vs. 45.5 ± 34.7 ms, p Discussion: HRV biofeedback can modulate autonomic cardiac function post AIS to increase HRV and alleviate autonomic symptoms which might be beneficial in facilitating recovery from functional impairment. This seems to be mediated by a predominantly parasympathetic mechanism of action.

Introduction: A recent exploratory analysis suggested comparable outcomes among ischemic stroke patients undergoing endovascular therapy (EVT) for anterior circulation large vessel occlusion (acLVO), regardless whether selected via telestroke or admitted directly to an EVT-capable stroke center. The aim of this study was to determine the benefit of EVT in prospectively registered telestroke patients undergoing EVT for acLVO. Methods: We studied consecutive patients with acLVO who underwent EVT at our tertiary stroke center between January 2016 and March 2018. All transferred patients received repeated vascular imaging at our center. We compared clinical and imaging variables as well as safety and efficacy outcomes including symptomatic intracranial hemorrhage (sICH), major reperfusion (mTICI 2b/3), 90-days favorable functional outcome (mRS ≤2) and 90-days survival between patients transferred from telestroke hospitals and patients directly admitted to our stroke center. Results: Of 513 prospectively registered ischemic stroke patients screened for EVT eligibility during the 27-months study period, 164 had acLVO and eventually underwent EVT: median age 76 years (interquartile range, 66-82); 46% men; median NIHSS score 17 (13-20) points. Of these patients, 73 (44.5%) were transferred from a telestroke hospital and 91 (55.5%) were directly admitted to our tertiary stroke center. While telestroke patients had longer onset-to-needle (median: 128 [95-150] vs. 103 [87-122] min; p=0.051) and onset-to-groin puncture (median: 295.5 [248-340] vs. 180 [132-220] min; 0.05) in clinical and imaging variables were present between the two groups. The rates of sICH (2.7% vs. 1.1%; p=0.586), major reperfusion (80.8% vs. 76.9%; p=0.545), 90-days favorable functional outcome (23.9% vs. 28.9%; p=0.481) and 90-days survival (73.2% vs. 67.0%; p=0.393) were similar between telestroke and directly admitted patients. Conclusions: Our prospective data confirms that telestroke and directly admitted ischemic stroke patients have comparable outcomes following EVT for acLVO.

Introduction: The selective serotonin reuptake inhibitors (SSRIs) fluoxetine, citalopram and escitalopram have been suggested to improve functional recovery after acute ischemic stroke (AIS) due to modulation of autonomic cardiovascular and inflammatory pathways independently of changes in depressivity. Although sertraline has shown highest degree of tolerability and efficacy among SSRIs in the treatment of depression, its effects on functional recovery from AIS remain unknown. Hypothesis: We hypothesized that sertraline is associated with improved functional recovery from AIS which is paralleled by alleviation of autonomic symptoms and depressivity. Methods: We analyzed data of an ongoing prospective observational study in AIS patients who were admitted to our stroke center from 03/2017 to 08/2018 and had no disability pre-stroke (mRS 0-1). Patients who received sertraline for post stroke depression or improvement of recovery following institutional protocol and those not receiving any SSRI were include. Assessment of cardiovascular risk factors, neurological deficits (NIHSS), symptoms of depression (Beck’s depression inventory) and autonomic disturbances (autonomic symptom questionnaire) were assessed at baseline, discharge and after three months. Results: We present data from 61 patients (70 [20] years, median [IQR], NIHSS: 7.0 [6.0], 23 females) receiving sertraline post-stroke and 27 untreated patients (71.0 [21.0] years, NIHSS: 5.0 [3.0], 13 females). Cardiovascular risk profiles showed no differences between groups (p=ns). Patients treated with sertraline compared to untreated patients tended to achieve favorable functional outcome (3-month mRS 0-2) and functional independence (3-month mRS 0-1) more frequently (52% vs. 41.7% and 18% vs. 12.5%, p=ns) and displayed enhanced decrease of NIHSS scores from admission to discharge (24.1% vs. 17.3%, p2 =0.63) symptoms after 3 months, independently of depressivity. Discussion: Our data support the hypothesis of improved functional recovery from AIS in patients receiving sertraline de novo after AIS which might in parts be mediated by modulation of autonomic pathways.

Introduction: While data from randomized controlled trials suggest an overall benefit of endovascular therapy (EVT) in older patients suffering from anterior circulation large vessel occlusion (acLVO), real world evidence is lacking. We aimed to explore the likelihood of achieving favorable stroke outcomes in octogenarians undergoing EVT for acLVO. Methods: We prospectively studied consecutive ischemic stroke patients aged 80 years or older who were considered for EVT due to acLVO at our tertiary stroke center (01/2016-06/2018). We compared clinical characteristics and efficacy outcomes including 90-days functional independence (i.e., mRS scores 0-2) and 90-days survival among patients who underwent EVT and those who did not undergo EVT. A multivariable regression model was built to identify predictors of favorable outcomes. Results: In total, 185 patients aged 80 years or older were prospectively screened for EVT eligibility during the 30-months study period: median age was 84 years (interquartile range, 82-88); 30% were men; median NIHSS score was 18 (interquartile range, 14-21) points. Of these patients, 97 (52.4%) were eventually treated for proximal acLVO. The main reasons to withhold EVT were large infarct size (54.6%) and recanalization (30.7%), followed by unknown time window (5.7%), lack of perfusion mismatch or collaterals (4.5%) and early clinical improvement (2.3%). No differences according to vascular risk factors, baseline imaging and clinical variables were evident among both groups. There was a non-significant trend toward survival (50.6% versus 37.3%, p=0.09) but not functional independence (9.9% versus 5.3%, p=0.39) at 90 days in patients who underwent EVT compared with the non-EVT group. In the multivariable model, favorable outcomes were not predicted by pre-stroke disability, stroke severity, infarct size or treatment with intravenous tPA. Conclusions: While age alone should not exclude patients from endovascular therapy, diminished likelihood of favorable outcomes may challenge postacute stroke care in octogenarians.

Background: Recent clinical trials have proven efficacy of endovascular therapy (EVT) for anterior circulation large vessel occlusion (acLVO). The DAWN and DEFUSE 3 trials have selected patients for EVT beyond 6h from symptom onset. We sought to determine how many patients of our center would qualify to apply advanced DAWN or DEFUSE 3 imaging criteria based on clinical symptoms and imaging with non-contrast CT (NCCT) and CT angiography (CTA). Methods: We prospectively registered consecutive ischemic stroke patients who were screened for EVT eligibility between 01/2016 and 12/2017. Of these patients, we identified those who fulfilled DAWN (age ≥18years, pre-morbid mRS score ≤1 , NIHSS score ≥10, onset-to-CT time 6-24 hours) and DEFUSE 3 (age 18- 90 years, pre-morbid mRS score ≤2, NIHSS score ≥6, onset-to-CT time 6-16 hours) inclusion criteria, respectively. Of these, we identified patients with acLVO on CTA and early ischemic changes in ≤1/3 of the middle cerebral artery territory (DAWN) or NCCT-ASPECTS >6 (DEFUSE-3), respectively. Results: Among 1011 patients who presented during the study period, 362 patients (36%) had an onset-to-CT time between 6-24 hours and 244 patients (24%) between 6-16 hours. Among the 6-24 hours cohort, 62 patients had an NIHSS score ≥10. Of these, 30 patients had acLVO of whom 13 patients had early ischemic changes ≤1/3 of the MCA territory on NCCT. Among the 6-16 hours cohort, 69 patients had an NIHSS score ≥6. Of these, 33 patients had acLVO of whom 18 patients had a NCCT-ASPECTS >6. Despite early ischemic changes in ≤1/3 of the MCA territory in 320 patients presenting >6 hours from symptom onset, no acute vascular imaging was performed in 108 patients. Overall, 19 patients (2% of the complete cohort) fulfilled clinical and imaging criteria utilized in DAWN or DEFUSE-3 trials. Of these, only 10 patients (1% of the complete cohort) received additional perfusion CT of whom 7 patients eventually underwent EVT. Conclusions: Only a minority (2%) of patients in our cohort would have qualified to apply advance imaging criteria based on DAWN or DEFUSE-3 trials for EVT beyond 6 hours from stroke onset. However, the positive results of these trials may have an impact on future assessment of EVT eligibility in patients presenting at a later time window.

Introduction: Density of hyperdense middle cerebral artery sign (HMCAS) quantified via Hounsfield units (HU) on CT may predict clot composition and stroke TOAST subtype, with clots from cardioembolism displaying lower HMCAS densities due to fibrin predominance than erythrocyte-dominant clots originating from large artery atherosclerosis (LAA). Hypothesis: We hypothesized that embolic stroke of undetermined source (ESUS) is linked to higher density of HMCAS due to its high probability of a cardiac source and that HMCAS as a surrogate marker of clot composition predicts successful reperfusion following endovascular therapy (EVT). Methods: We analyzed data from an ongoing prospective observational study (since 01/2016) in consecutive patients with acute ischemic stroke (AIS) undergoing EVT for proximal occlusion of the middle cerebral artery (MCA) detected on CT-angiography and confirmed on digital subtraction angiography. Stroke subtypes were determined according to TOAST and ESUS criteria. On thin-slice (1.5mm) non-contrast CT, a blinded neuroradiologist assessed average and maximum HU values for HMCAS. Multiple regression analyses were undertaken to explore the association of HMCAS density normalized for contralateral MCA (HMCAS ratio) with stroke subtypes and major reperfusion (TICI 2b/3) following EVT. Results: In this interim analysis 110 out of 253 patients were included (55.1% females, ages 74 [64-80], median [IQR], baseline NIHSS 17 [13-20], 76 with IVT before EVT) of which 19 (17.8%) had ESUS, 65 (60.8%) had cardioembolism and 23 (21.5%) had LAA. Density analyses showed HMCAS ratios of 1.26 ± 0.22 (mean ± SD) in the entire cohort with no differences among subgroups (ESUS: 1.19 ± 0.26, LAA: 1.24 ± 0.25, cardioembolic stroke: 1.29 ± 0.19, p = ns), the latter being also true for HMCAS ratios of maximum HU values and absolute HU values (p = ns). On multivariate regression model adjusted for intravenous tPA and onset to groin puncture time, HMCAS average ratio did not predict major reperfusion (per 1-unit HU increase: 2.13; [0.25-18.29], OR [95% CI]) or stroke subtype. Discussion: Density analysis of HMCAS appears not to be helpful in detection of ESUS, diagnostic discrimination between stroke subtypes, or prediction of reperfusion following EVT.

Introduction: While three randomized trials recently showed no difference in clinical outcomes between general anesthesia and conscious sedation in stroke patients undergoing endovascular therapy (EVT) for acute ischemic stroke, preliminary data suggest that anesthesia duration itself might adversely affect stroke outcomes. Therefore, we aimed to explore the impact of general anesthesia duration on functional outcome in stroke patients undergoing EVT for large vessel occlusion (LVO). Methods: We analyzed prospectively collected data from consecutive ischemic stroke patients who underwent EVT for LVO in the anterior circulation from 01/2016 to 06/2017. To investigate the sole effect of anesthesia, we excluded patients whose anesthesia lasted >= 72 hours (e.g., due to perceived course of malignant infarction) or was prolonged due to medical reasons (e.g., symptomatic intracranial bleeding, malignant infarction). Multivariate linear regression model adjusted for covariates was employed to evaluate whether modified Rankin Scale (mRS) scores at 3 months could be predicted by duration of anesthesia. Results: Of 155 ischemic stroke patients undergoing EVT for LVO during the study period, 82 received general anesthesia initiated prior to or during the procedure. Of these patients, 68 fulfilled our inclusion criteria: median age 75 years (IQR, 16); 46% men; median NIHSS score 18 (6); median ASPECT score 7 (2). The median duration of general anesthesia was 440 (1015) minutes and of ventilation/intubation 590 (2150) minutes. Multivariate linear regression analysis revealed that each minute increment in general anesthesia independently predicted mRS scores at 3 months (r 2 =0.368, F=5.13, p Conclusions: Prolonged anesthesia might negatively affect functional outcome after endovascular therapy in acute ischemic stroke patients undergoing endovascular therapy for large vessel occlusion.

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 at 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: A total of 120 patients (median age, 69 [IQR, 16] years; 74% men; median time between DUS and angiography, 1 day [IQR, 2.5]) provided 162 DUS/angiography carotid artery pairs for final analysis. On angiography, moderate stenosis was found in 48 (30%) and severe stenosis in 63 (39%) arteries. Sensitivity of DUS for detection of moderate and severe stenosis was 35% (95%CI, 22-51%) and 81% (69-90%), with a NPV of 77% (68-84%) and 85% (75-92%), respectively. Specificity was 89% (81-94%) and 97% (94-99%), with a PPV of 57% (37-75%) and 62% (51-73%), respectively. Considering the entire spectrum of the disease (0-100%), the Bland-Altman interval limit of agreement was 51% (Figure). Conclusions: At laboratories experienced with ultrasound grading of the extracranial ICA, the novel DEGUM multi-parametric ultrasonography criteria do not eliminate the need for a confirmatory test for identification of clinically relevant grades of the disease.

Introduction: Selection of patients for endovascular therapy (EVT) may depend on the hospital providing first line assessment. In our collaborative stroke network, we aimed to compare clinical characteristics and outcomes in ischemic stroke patients undergoing EVT who were transferred from telestroke hospitals following teleconsultation and in those transferred from hospitals providing on-site neurology service. Methods: We analyzed prospectively collected data from consecutive ischemic stroke patients who underwent emergent EVT at our comprehensive stroke center (01/2010 to 12/2014) after acute transfer from either telestroke hospitals or non-telestroke hospitals with on-site neurology service. We compared baseline characteristics, onset-to-EVT time, symptomatic intracranial hemorrhage (sICH), favorable functional outcome (mRS 0-2) at discharge and in-hospital mortality. Results: Among 133 transferred patients who underwent emergent EVT: median age 67 years (IQR, 15); 56% men; median NIHSS score 17 (21); 52% had anterior and 48% posterior circulation stroke. Sixty-five patients (49%) were transferred from telestroke and 68 (51%) from non-telestroke hospitals. Telestroke patients were less severely affected (median NIHSS scores: 15 [7] vs. 22 [20]; p=.0005) and more likely to have anterior circulation stroke (69% vs. 35%; p Conclusions: Patients transferred from telestroke hospitals were twice as often treated for anterior circulation stroke than those from non-telestroke neurological hospitals within our stroke network. This might be explained by more conservative selection of patients potentially amenable for EVT in hospitals harboring on-site neurology service but no EVT-capability. As our data was acquired prior to evidence from the positive EVT trials, further research is warranted to elaborate these findings.

Background: Although intravenous thrombolysis (IVT) with tissue plasminogen activator (tPA) and endovascular therapy (EVT) are considered standard-of-care treatment of acute ischemic stroke in adults, safety and efficacy of these treatment modalities in children is unknown to date. We reviewed current literature and synthesized data on safety and efficacy of IVT and EVT in children with ischemic stroke. Methods: We performed a systematic review and meta-analysis of all available case series and observational studies that evaluated safety of IVT and EVT in pediatric stroke patients aged less than 18 years. We searched the electronic databases Medline, PubMed, Cochrane Library, Google Scholar for eligible studies. Safety outcomes comprised any intracerebral hemorrhage post-treatment and in-hospital mortality. A random-effects model was used to compute pooled effect estimates and the I 2 statistic was used to assess heterogeneity. Our analysis complied with PRISMA statement. Results: We identified 152 records through database searching, of which only 3 studies with a total of 16,335 pediatric patients with ischemic stroke met our eligibility criteria. Of these studies, two explored safety of sole IVT and one combinatory IVT/EVT. In-hospital mortality rates were similar between pediatric stroke patients treated with either IVT or IVT/EVT and controls (odds ratio=0.85, 95%CI: 0.15-4.87; p=0.857), with moderate evidence of heterogeneity ( I 2 =64%). Risk of intracerebral hemorrhage was substantially increased in children receiving IVT (odds ratio=3.60, 95%CI: 1.66-7.80; p=0.001) compared with controls, with no evidence of heterogeneity ( I 2 =0%). Efficacy of revascularization therapies could not be analyzed due to lack of uniform outcome data in the included studies. Conclusions: Our synthesized data analysis revealed a substantial lack of evidence for acute revascularization treatment of children with ischemic stroke. While an increased risk of intracerebral hemorrhage related to IVT emerged in our analysis, further research is needed to elaborate these findings.

Background & Purpose: The safety and efficacy of direct oral anticoagulants (DOAC) for the prevention of thromboembolism in patients with non-valvular atrial fibrillation (NVAF) have been compared to vitamin-k antagonists (VKA) in randomized-controlled clinical trials. There are limited data regarding neuroimaging profile and outcomes in intracerebral hemorrhage (ICH) occurring during DOAC treatment. We sought to compare neuroimaging findings and outcomes in VKA- and DOAC-related ICH. Methods: We prospectively evaluated consecutive NVAF patients with non-traumatic, anticoagulant-related ICH that were admitted during a 1-year period in 9 stroke centers. Baseline hematoma volume was calculated by ABC/2 formula. Baseline stroke severity and 3-month functional outcome (FO) were assessed using NIHSS- and mRS-scores. The ICH severity was determined using ICH-score (severe ICH: ICH-score of 3-5). Results: We evaluated 91 patients with ICH due to DOAC (n=30) or VKA (n=61). The two groups did not differ in demographic, vascular risk factors, HAS-BLED & CHA2DS2-VASc scores, antithrombotic medications with the exception of higher renal failure prevalence in VKA (28% vs. 4%). DOAC group had significantly (p3 ). The rates of severe ICH (13% vs. 34%), perihematomal edema (44% vs.74%), midline shift (20% vs. 49%), 3-month disability (mRS-score: 3-6; 37% vs. 64%) and 3-month mortality (10% vs. 35%) were significantly (p>0.05) higher in VKA group. DOAC-related ICH was independently (p Conclusion: DOAC-related ICHs appear to have more favorable neuroimaging profile and functional outcome compared to VKA-related ICHs.

Background: The diagnostic value of cerebrospinal fluid (CSF) analysis in identification of stroke etiology in patients with juvenile stroke remains not well studied. We sought to determine the frequency and underlying causes of pathological CSF-findings in juvenile stroke patients who underwent CSF-analysis as part of their diagnostic work-up. Methods: We retrospectively abstracted data from consecutive (01/2008 to 12/2015) patients aged 18 to 45 years with acute ischemic stroke or transient ischemic attack. Routine work-up included MRI with dissection-sensitive sequences, Holter-ECG, transthoracic and transesophageal echocardiography, duplex ultrasound of extra- and intracranial arteries and screening for coagulopathies, vasculitis and Fabry disease. CSF-analysis was routinely performed in patients with hitherto cryptogenic stroke. We assessed frequency and causes of pathological CSF-findings including microbiological and virological abnormalities, and their impact on the choice of specific therapy for secondary stroke prevention. Results: Among 379 juvenile patients with acute ischemic stroke or transient ischemic attack, CSF analysis was performed in 201 patients (53%). Of these, 26 patients (13%) had CSF pleocytosis (leucocyte cell count ≥5 Mpt/l). CSF-pleocytosis was rated false positive (e.g. traumatic lumbar puncture, reactive pleocytosis due to acute stroke) after exclusion of specific conditions in 23 of these patients. Only 2 patients with CSF-pleocytosis (1% of patients who underwent CSF analysis) had specific CSF-findings (Lyme disease and neurosyphilis with consecutive cerebral vasculitis) as a cause of stroke and subsequent impact on secondary stroke prevention therapy. One patient had serological evidence of chronic infection with Mycoplasma pneumoniae that was rated as a contributing factor to stroke pathophysiology. Conclusions: The diagnostic yield of routine CSF-analysis in juvenile stroke patients was remarkably low in our study. Our data suggest that CSF-analysis should only be performed if further findings raise the suspicion of cerebral vasculitis.

Introduction: It has recently been shown that insertable cardiac monitors (ICM) reveal intermittent atrial fibrillation (AF) in up to 12.4% of patients with embolic stroke of undetermined source (ESUS) at 1 year follow-up. We sought to analyze the detection rate of intermittent AF with ICM in real-life clinical practice. Methods: We prospectively studied consecutive patients with ESUS who received an ICM (NeuroLinq®) from 01/2014 to 06/2015). Baseline characteristics, treatment modalities and AF detection rate in the first year following ICM placement was assessed. Results: We enrolled 75 ESUS patients (64% men, median age 61 years) who underwent ICM placement. Two patients were excluded due to diagnosis of prion disease and Churg-Strauss syndrome after placement of ICM. Sixty-nine of 73 (95%) patients complied with the eligibility criteria adopted by the CRYSTAL-AF study. Intermittent AF was detected in 14 (19%) patients with a median time from ICM placement to diagnosis of 57 (range, 312) days. Conclusions: Our data suggest that the real-life detection rate of intermittent AF with ICM placed in patients with ESUS is comparable to that one observed under clinical trial conditions.

Introduction: The novel multi-parametric ‘DEGUM’ duplex ultrasonography (DUS) criteria may improve accuracy of extracranial carotid artery grading but have not been compared with the established Society of Radiologists in Ultrasound (SRU) consensus criteria yet. We sought to investigate the diagnostic agreement between these two widely used DUS approaches for grading of carotid artery steno-occlusive disease. Methods: This was a sub-analysis of the complete dataset from a prospective multicenter study, where a total of 120 patients underwent both DUS and catheter angiography for validation of the multi-parametric DEGUM ultrasound approach. In this analysis, two ultrasonography experts independently interpreted documented B-image, color-flow and Doppler spectra findings utilizing DEGUM and SRU criteria. Carotid arteries were categorized into clinically relevant NASCET strata: moderate (50-69%), severe (70-99%) and occlusion. On angiography, ICA was graded using the NASCET approach. Inter-rater and between-methods reliability was assessed through weighted Cohen’s kappa. Overall accuracy for both ultrasound approaches was computed using catheter angiography as the gold standard. Results: We analyzed a total of 162 carotid artery pairs on catheter angiography and DUS. There was almost perfect agreement between both ultrasonography diagnostic approaches in describing all clinically relevant grades of the disease (k w 0.91, CI95%: 0.89-0.94). Inter-rater reliability was found to be comparably high for both the DEGUM (k w 0.97, CI95%: 0.94-0.98) and the SRU (k w 0.98, CI95%: 0.97-0.99) ultrasonography approaches. Compared with catheter angiography, overall accuracy for moderate and severe stenosis ranges did not differ between the DEGUM (73% and 73%, respectively) and the SRU (73% and 70%, respectively) approaches. There was also no difference for detection of carotid artery occlusion (96% and 96%, respectively). Conclusions: Our analysis showed almost perfect diagnostic agreement between the DEGUM and the SRU approaches for ultrasonography grading of carotid artery steno-occlusive disease. Therefore, our data do not support superiority of one approach over the other in the evaluation of clinically relevant grades of the disease.

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.

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.

Objective: We sought to determine the safety of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients harboring unruptured intracranial aneurysm (UIA) in a prospective, multi-center study. Methods: We prospectively analyzed data from consecutive AIS treated with IVT during a 4-year period at four tertiary-care stroke centers. All patients routinely underwent CT or MR angiography during hospitalization. The presence of UIA was documented on the basis of neuroradiology reports. Symptomatic intracranial hemorrhage (sICH) was defined as imaging evidence of ICH combined with an increase in NIHSS-score of ≥4 points. Results: Our multicenter study evaluated a total of 1398 AIS patients treated with IVT with available neurovascular imaging data. The presence of concomitant UIAs was identified in 42 cases (3.0%, 95%CI by adjusted Wald method: 2.2%-4.1%) harboring a total of 48 IAs. Four of the forty-two (8%) AIS patients had multiple aneurysms. The mean maximum diameter of UIA was 4.3±2.7mm ranging between 2-15 mm. Nearly all UIA were saccular (45/48, 94%) and the majority were located in the anterior circulation (29/48; 61%). The maximum diameter was ≥7mm and ≥10mm in 6 (12.5%) and 3 (6.3%) cases respectively. The rates of symptomatic and asymptomatic ICH were 2.4% (95%CI by adjusted Wald method: 0%-12.6%) and 7.1% (95%CI by adjusted Wald method: 1.8%-19.7%) respectively. The single sICH reported in our multi-center study was not caused by aneurysmal rupture, since the incidental aneurysm was located in the posterior communicating artery in the hemisphere that was contralateral to the sICH. The rates of in-hospital mortality and favorable functional outcome at hospital discharge (defined as modified Rankin Scale score of 0-1) were 2.4% (95%CI by adjusted Wald method: 0%-12.6%) and 50.0% (95%CI by adjusted Wald method: 35.5%-64.5%) respectively. Conclusions: Our prospectively collected multi-center data indicate the potential safety of IVT in AIS patients with UIA.

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

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: Frequency of sleep-disordered breathing (SDB) among stroke and TIA patients ranges from 50% to 94%, and is associated with poor neurological outcomes. Per current stroke prevention guidelines from American Stroke Association, SDB is included in the list of modifiable risk factors for stroke and TIA prevention. The goal of our study was to determine screening practices for SDB in stroke medical community. Methods: A web-based survey was conducted between 12/2013 to 7/2014 among practitioners taking care of stroke patients across United States and Europe. Results: Among 112 total responses (18%), 91 were stroke physicians (81.25%), 9 were general neurologist (8.04%), 3 were sleep medicine physicians (2.68%) and 9 were other specialty (8.04%). Majority of practitioners (72%, n= 81) do not use SDB screening questionnaires in their stroke patients. Epworth sleepiness scale is the most used among SDB questionnaires (24%), followed by Berlin sleep questionnaire (9.5%) and STOP-BANG questionnaire (7%). Only 12% of practitioners use screening questionnaires in both in-patients and out- patients, where as 20% use only in out- patients and 5% use only in acute stroke setting. Only 50% of practitioners would refer their stroke patients to a sleep medicine specialist when patients were screened positive for SDB on questionnaires. Conclusion: Despite being an independent risk factor for stroke and TIA, majority of practitioners do not screen stroke and TIA patients for SDB. Further work is needed to improve screening practices for SDB in stroke medical community.

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.

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.

Background/Purpose: External counterpulsation (ECP) has been cited as a method that may improve brain perfusion and functional outcome in ischemic stroke. We sought to understand the tolerability and safety of ECP within 48 hours of ischemic stroke. Methods: A randomized, patient-blinded design was used in MCA strokes ineligible for reperfusion arriving within 46 hours of stroke onset at 3 CSCs. A 1-hour ECP session (ViaCare, Scottcare Inc.) was provided with 200-300 mm Hg pressures in treatment group patients, and the lowest device pressure with air-leak cuffs in shams. TCD and NIHSS measures were collected before, during and after ECP; patients were followed for 30-days post-treatment. Results: 23 patients were randomized (13 treatment; 10 sham); age (mean 58+12), race (78% White; 74% non-Hispanic) and gender (65% male) were similar between groups, baseline NIHSS was 6 in treatment cases and 6.5 in sham patients (p=ns), and all other baseline measures were similar between groups. There was no difference in time to ECP between groups. During ECP, an unexpected increase in sham group PSV, EDV, MFV, and proportional velocity change (PVC) was observed, with very little augmentation of MFV or PVC observed in the treatment group (Table). Tolerability was 100% in shams vs. 92% in the treatment group, with 54% sustained tolerance during high pressure. A >2 point NIHSS decrease during ECP occurred in 70% of shams vs. 38% of treatment group patients, and persisted at 30 days; mRS and Barthel indices at 30-days were similar between groups (Figure). One adverse event (AE) occurred in each group, and 1 treatment group patient had 3 serious AEs. No sICH, new ischemic strokes, or deaths occurred. Conclusions: ECP is safe in acute ischemic stroke, although 60-minute sustained tolerance of higher pressures remains questionable. The ViaCare device did not augment MFV compared to our experience with other ECPs. Sham arms should be cautiously undertaken in the future designs of ECP studies.

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.

Background and Purpose— We aimed to evaluate safety and tolerability of a novel operator-independent ultrasound device among stroke-free volunteers. Methods— A headframe containing 18 ultrasound transducers (each operating at 2 MHz, pulsed-wave) was used to expose both temporal windows and the suboccipital window. The transmission characteristics were set to emulate the acoustic characteristics of the exposure levels in the Combined Lysis of Thrombus in Brain Ischemia using Transcranial Ultrasound and Systemic tPA (CLOTBUST) trial and to never exceed Food and Drug Administration mandated diagnostic ultrasound exposure limits. Volunteers underwent 2 hours of insonation with transducer activation one at a time. Safety was captured using serial neurological examinations and pre- and postinsonation MRI for detection of the blood brain barrier permeability. Results— A total of 15 volunteers (40% men; 49±16 years; 27% black; all pre-exposure National Institutes of Health Stroke Scale scores 0) were enrolled. Five volunteers received pulsed-wave ultrasound via the best pair temporal transducers, 5 via sequential activation of the suboccipital transducers, and 5 via sequential activation of all bilateral temporal and suboccipital transducers. All subjects were safely insonated with no adverse effects as indicated by the neurological examinations during, immediately after the exposure, and at 24 hours, and no abnormality of the blood brain barrier was found on any of the MRIs. Conclusions— Our novel device was well tolerated by stroke-free volunteers and did not cause any neurological dysfunction nor did it affect blood brain barrier integrity. The safety and efficacy of the device are now being tested in stroke patients receiving intravenous tissue-type plasminogen activator in phase II–III clinical trials.

Background and Purpose— We sought to evaluate the diagnostic accuracy of ultrasound criteria for recanalization during real-time transcranial Doppler monitoring of intra-arterial reperfusion procedures in acute ischemic stroke patients in an international, multicenter study. Methods— Consecutive acute ischemic stroke patients with proximal intracranial occlusions underwent intra-arterial reperfusion procedures with simultaneous real-time transcranial Doppler monitoring at 3 tertiary-care stroke centers. Residual flow signals at the site of angiographically confirmed occlusions were monitored at a constant transtemporal insonation angle using a standard head-frame. Recanalization was assessed simultaneously by digital subtraction angiography and ultrasound using thrombolysis in myocardial infarction and thrombolysis in brain ischemia (TIBI) criteria, respectively. Independent readers blinded to digital subtraction angiography performed validation of TIBI flow grades. The interrater reliability for assessment of TIBI grades was investigated. Results— We evaluated time-linked real-time digital subtraction angiography transcranial Doppler images from 96 diagnostic digital subtraction angiography runs during intra-arterial reperfusion procedures in 62 acute ischemic stroke patients (mean age, 59±17 years; 58% men; median baseline National Institutes of Health Stroke Scale score, 18 [interquartile range 12–21]; median time from symptom onset to intra-arterial procedure initiation, 240 minutes [interquartile range 163–308]). The interrater reliability for evaluation of TIBI grades and assessment of recanalization was good (Cohen κ : 0.838 and 0.874, respectively; P Conclusions— At laboratories with high-interrater reliability, TIBI criteria can accurately predict brain recanalization in real time as compared with thrombolysis in myocardial infarction angiographic scores.

Background&Purpose: A recent meta-analysis showed that sonothrombolysis is safe and can double the rate of early recanalization in acute ischemic stroke (AIS). We sought to explore whether patients with severe strokes could clinically benefit from ultrasound amplification of tPA-induced recanalization. Subjects&Methods: We compared functional outcomes at 3 months among randomized AIS patients with pre-treatment NIHSS scores >=10 in the Combined Lysis of Thrombus in Brain Ischemia (CLOTBUST), Transcranial Ultrasound in Clinical Sonothrombolysis (TUCSON) and pilot randomized clinical safety study of sonothrombolysis with microspheres (Definity study). Patients had proximal arterial occlusions identified by baseline TCD and received intravenous (IV) tPA or IV tPA plus continuous 2-hour TCD ultrasound monitoring (=sonothrombolysis). Favorable outcome was defined as modified Rankin Scale (mRS) 0-1 at 3 months. Sustained complete recanalization was defined as Thrombolysis in Brain Ischemia (TIBI) flow grades 4-5 assessed by TCD at 2 hours after tPA bolus. Symptomatic intracranial hemorrhage (sICH) was defined using ECASS-2 definition as imaging evidence of ICH with clinical worsening (NIHSS >=4) within 72 hours from stroke onset. Results: A total of 139 AIS patients with severe stroke due to proximal arterial occlusions (mean age 69±13years, 56% men, median NIHSS 17, interquartile range 14-21, range 10-34) were randomized in CLOTBUST (n=105), TUCSON (n=21) and Definity (n=13). A total of 60 (43%) and 79 (57%) patients were randomized to IV tPA and sonothrombolysis, respectively. Patients treated with IV tPA and sonothrombolysis did not differ in terms of age, baseline stroke severity, baseline TIBI grades and onset-to-treatment time. Symptomatic ICH rates were similar in patients treated with IV tPA and sonothrombolysis (5.0% vs. 5.1%; p=0.987). More patients achieved sustained complete recanalization in the sonothrombolysis than in the IV tPA group (38.0% vs. 18.3%; p=0.012). Favorable outcome (mRS 0-1) tended to be more prevalent in the sonothrombolysis than in the IV tPA group (36.6% vs. 23.2%; p=0.104). Conclusions: Our data point to a signal-of-efficacy and provide basis to determine the sample size of a phase 3 randomized trial of sonothrombolysis in patients with severe strokes ( NCT01098981 ).

Background & Purpose: Recent observational data showed that delayed (>6 hours) recanalization in acute ischemic stroke (AIS) patients treated with systemic thrombolysis may be associated with a higher risk of symptomatic intracranial hemorrhage (sICH). We sought to investigate the relationship of persisting occlusion during the first two hours of iv-tPA and the likelihood of sICH using pooled data from three randomized sonothrombolysis studies. Subjects & Methods: We evaluated the risk of sICH among AIS patients randomized in the Combined Lysis of Thrombus in Brain Ischemia (CLOTBUST), Transcranial Ultrasound in Clinical Sonothrombolysis (TUCSON) and a pilot randomized clinical safety study of sonothrombolysis augmentation with ultrasound-activated perflutren-lipid microspheres (Definity study). Acute proximal arterial occlusions were identified in all patients at baseline using Trancranial Doppler (TCD). Patients underwent continuous or intermitted TCD-monitoring for a two-hour period following tPA-bolus. Persisting occlusion was defined as absence of improvement of baseline TIBI flow grade at the end of TCD-monitoring. sICH was defined using ECASS-2 definition as imaging evidence of ICH with clinical worsening (NIHSS≥4) within 72 hours from stroke onset. Results: A total of 176 AIS patients (mean age 68±14years, 57% men, median baseline NIHSS-score 16 points, interquartile range 11-20) were randomized in CLOTBUST (n=126), DEFINITY (n=15) and TUCSON (n=35). A total of 75 (43%) and 101 (57%) individuals were randomized to systemic thrombolysis and sonothrombolysis respectively. Persisting occlusion was identified at the end of TCD-monitoring in 65 patients (37%). Patients with persisting occlusion tended to have higher sICH rates compared to individuals with partial or complete recanalization (9.2% vs. 2.7%; p=0.078 by Fisher’s exact test). After adjusting for demographic characteristics, onset-to-treatment time, baseline stroke severity, baseline TIBI flow grade and treatment (sonothrombolysis vs. systemic thrombolysis) persisting occlusion was independently associated with a higher likelihood of sICH (OR:6.29, 95%CI:1.28-30.85; p=0.024). Conclusions: Failure to recanalize during the first two hours following tPA-bolus appears to increase sICH risk among AIS treated with standard systemic thrombolysis and sonothrombolysis. Possible mechanisms (elevated blood pressure with persistent occlusion and late, potentially harmful recanalization causing reperfusion injury to infracted brain tissue) are now subject of a prospective multicenter study (CLOTBUST-PRO).

Background&Purpose: Strokes in young adults differ from cerebrovascular events in the general population due to a wider variety of etiopathogenic mechanisms as well as by incidence and outcomes. Limited data exist regarding racial disparities in stroke outcomes in this specific age subgroup. We sought to prospectively evaluate potential racial disparities in early outcomes of young individuals with stroke in a multicenter, international study. Subjects&Methods: We prospectively evaluated consecutive first-ever stroke patients aged 18-45 years old who were admitted in 7 tertiary care stroke centers in North America (n=2), Europe (n=3) and Asia (n=2) over a four-year period (2008-2011). Demographics, vascular risk factors, etiopathogenic mechanism of stroke and stroke severity at hospital admission (assessed using the NIHSS-score) were documented. Early functional outcome at 1 month following stroke onset was evaluated using modified Rankin Scale (mRS) score. Results: A total of 826 young adults (mean age 37±7years; 60% men; 49% Caucasians, 19% African-Americans and 32% Asians; median baseline NIHSS-score 6 points, interquartile range 3-14) have been evaluated during the study period with first-ever ischemic (84%) or hemorrhagic (16%) stroke. Baseline stroke severity differed between Caucasians (median NIHSS-score 4 points, interquartile range 2-10), African-Americans (median NIHSS-score 7 points, interquartile range 3-15) and Asians (median NIHSS-score 9 points, interquartile range 5-14; p Conclusions: Racial disparities in early functional outcome following first-ever stroke in young individuals appear to be independent of other known outcome predictor variables. Asian young adults with stroke tend to have a lower likelihood to achieve functional independence at 30 days following stroke onset. The underlying mechanisms of the former association deserve further investigation.

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&Purpose: Microembolic signals (MES) on transcranial Doppler (TCD) are an independent risk factor for recurrent stroke and neurological deterioration in patients with extracranial symptomatic and asymptomatic carotid artery disease (CARAD). Clopidogrel load (300mg) combined with dual antiplatelet therapy has been shown to reduce asymptomatic embolization in patients with symptomatic CARAD. We sought to determine feasibility of clopidogrel load in decreasing asymptomatic embolization in patients with symptomatic CARAD undergoing urgent CEA within the first 8 days from the index event. Subjects&Methods: Consecutive patients with symptomatic CARAD (70%-99% stenosis) and presence of MES on 1-hour baseline ( Results: A total of 9 symptomatic CARAD patients (mean age 66±6years, 89% men, 56% ischemic strokes, median NIHSS 4 points, interquartile range 0-8, 44% TIAs) were treated with clopidogrel load followed by dual (66%) or single (33%) antiplatelet therapy. MES count was significantly reduced between baseline ( Conclusions: Our pilot study shows feasibility of administering clopidogrel load followed by dual or single antiplatelet therapy to reduce asymptomatic embolization in patients with symptomatic CARAD who are scheduled to undergo urgent CEA. The present findings are subject of a larger ongoing multi-center study.

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.