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Robot-assisted gait training following acute stroke could allow patients with severe disability to receive a high dosage and intensity of gait training compared with conventional physical therapy (CP). However, given the limited data on gauging the efficacy of Hybrid Assistive Limb (HAL) on gait training in patients with acute stroke, we aimed to evaluate several outcome measures following gait training with HAL. Patients with first-ever stroke, who required a walking aid and were able to start gait training within 1 week of stroke onset were included in the current study. Patients were assigned to either the CP or HAL group. Outcome measures were collected at baseline, and at the 2nd (at 2–6 weeks), and 3rd (at 3–5 months) assessments. All patients underwent physical therapy until the 3rd assessment; patients in the HAL group underwent gait training using HAL until the 2nd assessment. Thirty-seven patients (19 from CP and 18 from HAL, median age = 69 years) completed the study. At the 2nd assessment, the total Functional Independence Measure (FIM) score was higher in the HAL group than in the CP group (90.1 vs. 79.0, p = 0.042). In conclusion, the FIM scale could be used to identify responsiveness to acute stroke rehabilitation using HAL. • Hybrid Assistive Limb (HAL) promotes functional recovery post-stroke. • There is limited published data on the efficacy of HAL on gait training post-stroke. • The FIM scale is useful to gauge efficacy of HAL for acute stroke rehabilitation. [ABSTRACT FROM AUTHOR]

Purpose: Carbon dioxide (CO 2) is a potent cerebral vasomotor agent. Despite reduction in CO 2 levels (hypocapnia) being described in several acute diseases, there is no clear data on baseline CO 2 values in acute stroke. The aim of the study was to systematically assess CO 2 levels in acute stroke. Material and methods: Four online databases, Web of Science, MEDLINE, EMBASE and CENTRAL, were searched for articles that described either partial pressure of arterial CO 2 (PaCO 2) and end-tidal CO 2 (EtCO 2) in acute stroke. Results: After screening, based on predefined inclusion and exclusion criteria, 20 studies were retained. There were 5 studies in intracerebral hemorrhage and 15 in ischemic stroke, totalling 660 stroke participants. Acute stroke was associated with a significant decrease in CO 2 levels compared to controls. Cerebral haemodynamic studies using transcranial Doppler ultrasonography demonstrated a significant reduction in cerebral blood flow velocities and cerebral autoregulation in acute stroke patients. Conclusion: The evidence from this review suggests that acute stroke patients are significantly more likely than controls to be hypocapnic, supporting the value of routine CO 2 assessment in the acute stroke setting. Further studies are required in order to evaluate the clinical impact of these findings. • Changes in arterial partial pressure of carbon dioxide have a potent effect on the cerebral vasculature. • There remains no clear data on baseline carbon dioxide values in acute stroke. • Acute stroke patients are significantly more likely than controls to be hypocapnic. • This supports the value of routine CO 2 assessment in the acute stroke setting. [ABSTRACT FROM AUTHOR]

Abstract Goal We performed a systematic review and meta-analysis aiming to clarify the relationship between acid-suppressive medication (ASM) and the risk of pneumonia in acute stroke. Methods The included studies examined patients with an acute ischemic and/or hemorrhagic stroke, assessed the relationship of one or both groups of ASM, histamine-2 receptor antagonist (H2RA) and proton-pump inhibitor (PPI), as a variable of interest, and used the occurrence of hospital-acquired pneumonia (HAP) as an outcome measure. The search was conducted in MEDLINE, Cochrane, Embase, and Google Scholar. Random-effects meta-analyses were used to obtain pooled estimates of the effect. Results 5 retrospective cohort-studies fulfilled study criteria. The results revealed a higher risk of pneumonia for both, patients receiving PPI (adjusted relative risk [RR] 2.37, 95% confidence interval [CI] 1.36–4.17, I 2 0%) and H2RAs (adjusted RR 1.73, 95% CI 0.74–4.25, I 2 68.3%), although the latter did not reach statistical significance. A comparison of the overall acid versus non-acid groups using unadjusted values yielded likewise an increased risk for pneumonia for patients receiving ASM (unadjusted RR 4.65, 95% CI 1.64–13.16, I 2 93. 3 %). Conclusion Results of this meta-analysis show an increased risk for HAP in acute stroke patients who receive ASM, particularly those exposed to PPIs. Larger, well-controlled studies in acute stroke populations are needed to establish a clearer association between ASM and HAP. These results, however, urge caution when prescribing ASM – especially to stroke patients considered to be at high risk for pneumonia. Highlights • Proton-pump inhibitors increase risk of hospital acquired pneumonia after stroke. • Link between H2 blockers and risk for pneumonia after stroke is not significant. • Acid-suppressive medication overall increase the risk for pneumonia after stroke. [ABSTRACT FROM AUTHOR]

Abstract Background and purpose The optimal dose of alteplase for acute ischemic stroke among geriatric patients is unclear. We aimed to assess the efficacy and safety of a low-dose (0.6 mg/kg) and standard-dose (0.9 mg/kg) alteplase for varying severity of Asian geriatric stroke patients. Methods The favorable functional outcome on day 90 after stroke onset, and the symptomatic intracranial hemorrhage (SICH) rate following 24–36 h of intravenous alteplase were measured. The baseline NIHSS of 4–8, 9–13, ≥14 were defined as mild, moderate, and high severity, respectively. Results Totally, 249 geriatric patients treated with low-dose (n = 108) and standard-dose (n = 141) alteplase. Compared to standard-dose alteplase, low-dose alteplase had decrease in favorable functional outcome (22.2% versus 34.8%), and no difference in SICH rates was observed. For mild severity patients, the mortality was significantly increased with standard-dose alteplase (the NNT/NNH = 22.9/8.0 for mild severity, the NNT/ NNH = 15.0/14.7 for moderate severity, and the NNT/NNH = 13.5/19.6 for high severity). Conclusions Standard-dose and low-dose alteplase were comparable in reducing major disability, but low-dose alteplase for mild stroke showed much reduced mortality on day 90 for octogenarians. Highlights • Totally, 249 geriatric stroke patients treated with low-dose of 0.6 mg/kg (n =108) and standard-dose (n =141) alteplase. • The stroke severity was defined by NIHSS of 4–8, 9–13, and ≥14 as mild (n =53), moderate (n =64), and high severity (n =128). • For mild severity, the low-dose group had much reduced mortality. The NNT (mRS 0–2) and NNH (mRS 6) were 22.9 and 8.0. • For moderate and high severity patients, the efficacy and safety between the low- and standard-dose groups were comparable. • The NNT/NNH was 15.0/14.7 for moderate severity, and was 13.5/ 19.6 for high severity. [ABSTRACT FROM AUTHOR]

To investigate whether ultra-early recombinant tissue-plasminogen activator (rt-PA) administration can improve patient outcomes on mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO). Participants comprised rt-PA-eligible 204 patients with internal carotid artery or middle cerebral artery occlusion in the SKIP trial, who were randomly assigned to receive mechanical thrombectomy alone or combined intravenous thrombolysis (rt-PA: alteplase at 0.6 mg/kg) plus mechanical thrombectomy. We assessed associations between onset-to-puncture time and onset-to-rt-PA administration time and frequency of favorable outcome at 90 days and any intracerebral hemorrhage (ICH) at 36 h after onset. As a cut-off onset-to-puncture time for favorable outcome, receiver operating characteristic curves defined 2.5 h (57% sensitivity, 62% specificity). For onset-to-puncture times ≤2.5 h and > 2.5 h, frequencies of favorable outcomes were 72% and 63% (p = 0.402) in patients with rt-PA therapy and 44% and 58% (p = 0.212) in patients without rt-PA therapy, respectively. In terms of onset-to-rt-PA administration time, frequencies of favorable outcomes among patients with ultra-early rt-PA administration at ≤100, >100 min after onset, and without rt-PA therapy with onset-to-puncture time ≤ 2.5 h, and with and without rt-PA therapy with onset-to-puncture time > 2.5 h were 84% and 64%, 63%, and 44% and 58%, respectively (p = 0.025). Frequencies of any ICH among those patients were 37% and 32%, 32%, and 63% and 40%, respectively (p = 0.006). Ultra-early rt-PA administration should improve patient outcomes on mechanical thrombectomy among patients with LVO. Relatively late rt-PA administration might increase the frequency of any ICH. • The benefits of rt-PA depend on the time of administration after stroke onset. • To investigate the impact of ultra-early rt-PA on clinical outcome before mechanical thrombectomy. • The rt-PA-eligible 204 patients with ICA or MCA occlusion were included. • Combined ultra-early rt-PA with thrombectomy had the best clinical outcome. • Relatively late rt-PA before thrombectomy might increase the frequency of any intracranial hemorrhages. [ABSTRACT FROM AUTHOR]

Abstract Objectives We aimed to develop and evaluate a hub-and-spoke model in the East Delhi by assessing knowledge and creating awareness through sensitization programs in target communities and among general physicians (GPs) along with implementation of a standard stroke management protocol (SMP) at our institute in order to extend the benefit of thrombolytic therapy. Methods We carried out a prospective interventional study using sensitization program comprising 1046 community participants and 101 GPs under “Saving the Brain Initiative” project. Network included one hub and six nearby spoke hospitals. The pre-awareness and post-awareness data along with clinical outcome of thrombolysis collected over 2012–2017 was analyzed. Results We observed lack of awareness in communities and among GPs regarding stroke symptomatology and treatment options. There was 17.3% increase in patients with stroke post-awareness programs. Door-to-door time improved as 49.3% of patients reached hospital within <2 h of onset as compared to 32.2% in pre-awareness period. 89.4% patients had good outcome and were discharged with improved NIHSS. In the post-awareness period, the rate of thrombolysis increased by 4.0%. Conclusions Sensitization of primary physicians, paramedical and medical staff along with community dwellers and implementation of SMP through hub-and-stroke model is instrumental in improving the rate of thrombolysis and its outcome. Highlights • Strengthened the stroke pathways through “Saving the Brain Initiative” • Created hub-and-spoke stroke management model • Overcame the identified barriers for effective IVT in acute stroke management • Conducted awareness programs in communities and among general physicians • Proposed stroke management model for resource-limited settings [ABSTRACT FROM AUTHOR]

Background and purpose Long-term follow-up of large trials have confirmed the superiority of endovascular thrombectomy (ET) for treating acute ischemic stroke (AIS). However, it is still unknown whether these results can be generalized to clinical practice. In this study, we aimed to determine the long-term outcomes of AIS post-ET in the real-world clinical practice. Methods This observational study is based on a single-center prospective registry study. AIS patients were treated with second-generation stent retrievers from December 2012 to April 2016. The primary outcome was modified Ranks scale (mRS) at the time of the latest assessment. Favorable outcome was defined as mRS scores 0–2, and the unfavorable outcome was defined as mRS scores 3–6. Results Eighty-nine AIS subjects with large artery occlusion in anterior circulation undergoing ET were eligible for analysis. Median follow-up duration was 20 months (interquartile range 6–32), and 47 subjects (53%) achieved favorable outcome whereas 17 subjects (19%) were functional dependence and 25 subjects (28%) died. Independent predicators for long-term unfavorable outcome were higher baseline National Institutes of Health Stroke Scale (NIHSS) score (odd ratio:1.21;95% confidence interval 1.09–1.35; p < 0.001) and symptomatic intracerebral hemorrhage (sICH) (odd ratio:16.45;95% confidence interval 1.34–193.44; p = 0.026). More subjects of large-artery-atherosclerosis underwent permanent intracranial stenting (22%vs.10%) as compared with those of cardioembolism, while subjects of cardioembolism were more likely to experience sICH (13%vs.8%) and died (32%vs.16%). Conclusions Over half of AIS patients can achieve favorable long-term outcomes post-ET. Higher baseline NIHSS scores and sICH are independently associated with unfavorable outcome. Overall, clinical practice in this single canter can replicate the long-term outcomes from the published endovascular clinical trials. [ABSTRACT FROM AUTHOR]

Multiple trials have shown that mechanical thrombectomy (MT) is superior to medical therapy. However, no robust evidence is available regarding MT beyond 24 h. In this study, we aimed to determine the safety and efficacy of endovascular stroke therapy in this late window. We conducted a retrospective study of prospectively collected data of patients who met extended window trial criteria, but underwent MT beyond 24 h. Safety and efficacy outcomes included symptomatic intracerebral hemorrhage (sICH), procedural complications, number of passes, successful recanalization (mTICI 2b − 3), delta (Δ) NIHSS (baseline-discharge), and favorable outcomes (mRS 0–2 at 90 days). A total of 39 patients were included with a median age of 69 years (IQR 61.5, 73.5); 54% were females. Hypertension was present in 76% of patients; 23% were smokers. Half of the patients had M1 occlusion (48.7%). Median preprocedural NIHSS was 11 (IQR 7.0, 19.5). Successful revascularization was achieved in 87%; median number of passes was 2 (IQR 1.0, 3.0). Median ΔNIHSS was 3.0 (IQR -1.5, 8.0). Favorable outcome was achieved in 49% (95% CI: 34%–64%), and 95% were free of complications. A total of 3 patients (7.7%) had sICH. In an exploratory analysis, posterior circulation occlusion was associated with higher mRS at 90 days (OR: 14.7, p = 0.016). Favorable discharge facility was associated with lower mRS at 90 days (OR: 0.11, p = 0.004). Our study showed comparable clinical outcomes of MT beyond 24 h compared to MT trials within 24 h in patients with favorable imaging profile, especially in anterior circulation occlusions. • Mechanical thrombectomy performed over 24 h of stroke onset showed favorable outcomes and safety. • Results were comparable to previously published large studies within 24 h. • Imaging selection was utilized based on prior published studies and recommendations. [ABSTRACT FROM AUTHOR]

Background The only pharmacological treatment with proven cost-effectiveness in reducing acute ischemic stroke (AIS) associated disability is intravenous thrombolysis with recombinant tissue plasminogen activator but it's utilization rate is still low in most of the world. We estimated the minimum thrombolysis utilization rate needed to decrease the prevalence of stroke-related disability at a population level by using a discrete-event simulation model. Methods The model included efficacy according to time to treatment up to 4.5 h, and four scenarios for the utilization of intravenous thrombolysis in eligible patients with AIS: a) 2%; b) 12% c) 25% and d) 40%. We calculated the prevalence of AIS related disability in each scenario, using population based data. The simulation was performed from 2002 to 2017 using the ARENA software. Results A 2% utilization rate yielded a prevalence of disability of 359.1 per 100,000. Increasing thrombolysis to 12% avoided 779 disabled patients. If the utilization rate was increased to 25%, 1783 disabled patients would be avoided. The maximum scenario of 40% decreased disability to 335.7 per 100,000, avoiding 17% of AIS-related disability. Conclusion The current utilization rate of intravenous thrombolysis of 2% has minimal population impact. Increasing the rate of utilization to more than 12% is the minimum to have a significant population effect on disability and should be a public policy aim. [ABSTRACT FROM AUTHOR]

Background Because patients with warfarin-associated intracerebral hemorrhage (WAICH) have a high risk of ongoing bleeding, disability, and death, urgent coagulopathy reversal should be considered. On the other hand, thromboembolism may occur with reversal or withholding of anticoagulant therapy. The current status of acute hemostatic treatments and clinical outcomes in WAICH patients was investigated. Methods WAICH patients admitted within 3 days of onset were prospectively enrolled in 10 stroke centers. Thromboembolic and hemorrhagic complications and functional outcomes were followed-up for one year. Results Of 50 WAICH patients (31 men, 73 ± 9 years old) enrolled, all stopped warfarin on admission. Elevated prothrombin time-international normalized ratios (PT-INR) were normalized in 43 (86%). Anticoagulant therapy was resumed with intravenous full-dose unfractionated heparin followed by warfarin in 9 (18%), intravenous low-dose unfractionated heparin followed by warfarin in 14 (28%) and warfarin alone in 14 (28%) at a median of 2.5 (IQR 1.25–9), 4 (2–5.5) and 6 (3–11) days after onset, respectively, after emergent admission. Onset-to-admission time (per 1-hour increase; OR 0.55, 95% CI 0.19–0.84) was inversely associated with hematoma expansion. Anticoagulant therapy was resumed with intravenous full-dose unfractionated heparin in 9 (18%), low-dose heparin in 14 (28%) and warfarin alone in 14 (28%) at a median of 2.5, 4 and 6 days after onset, respectively. During one-year follow-up (n = 47), 11 thromboembolic and 6 hemorrhagic complications were documented. Twenty four patients showed unfavorable outcomes, corresponding to a modified Rankin Scale score of 4–6. Thromboembolic complications (OR, 10.62; 95% CI, 1.05–227.85), as well as advanced age (per 1 year; OR, 1.27; 95% CI, 1.10–1.61) and higher National Institutes of Health Stroke Scale (NIHSS) score (per 1 point; OR, 1.24; 95% CI 1.07–1.55), were independently associated with unfavorable outcome. Conclusions PT-INR normalization on admission and early anticoagulant resumption were common in WAICH patients. Thromboembolic complications were independently associated with unfavorable outcome. [ABSTRACT FROM AUTHOR]

Purpose Prognostic values of blood glucose levels following admission remain unclear. We investigated associations between blood glucose levels during the initial 72 h and outcomes of acute ICH. Methods Participants comprised hyperacute ICH patients who received intravenous antihypertensive treatment. Blood glucose levels were measured on admission and at 24 and 72 h after starting treatment, along with hemoglobin (Hb)A1c level on admission. Associations with clinical outcomes of hematoma expansion (> 33% increase), none to minimal disability (3-month modified Rankin Scale [mRS] 0–1) and bedridden or death (3-month mRS 5–6) were analyzed. Results Of the 176 patients (70 women; 65 ± 12 years), 30 (18%) showed hematoma expansion, and 33 (19%) had none to minimal disability and 15 (10%) were bedridden or died. On multivariate regression analysis, blood glucose at 24 h (per 10 mg/dl odds ratio [OR], 0.84; 95% confidence interval [CI], 0.69–0.98) and blood glucose at 72 h (OR, 0.75; 95%CI, 0.59–0.92) were inversely associated with none to minimal disability, and blood glucose at 24 h (OR, 1.14; 95%CI, 1.00–1.30) was positively associated with bedridden or death. No parameters were associated with hematoma expansion. Conclusions High blood glucose levels at 24 and 72 h were independently associated with poor functional outcomes 3 months after ICH. We need to investigate whether blood glucose control during the acute period ameliorates clinical outcomes. [ABSTRACT FROM AUTHOR]

Background Inflammation plays an important role in the development of ischemic stroke. We hypothesized that inflammation of carotid atherosclerosis, as measured by 18 F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET), associates with the early recurrent ischemic lesions (ERILs). Methods This prospective study included patients with symptomatic carotid atherosclerosis. ERILs were defined as newly developed ischemic lesions in the territory of symptomatic internal carotid artery stenosis, as detected by follow-up diffusion-weighted imaging (DWI). The patients with and without ERILs were compared in terms of risk factors, inflammatory markers, and FDG uptake on PET. Results Of the 21 patients, 8 had ERILs (38.1%). Compared to the patients without ERILs, those with ERILs had higher FDG uptake (maximum standardized uptake value, 3.07 ± 0.79 vs. 2.17 ± 0.68, p = 0.013) and were more likely to have irregular carotid plaques (100% vs. 38.5%, p = 0.007). Inflammatory markers were not different between the two groups, and also did not correlate with FDG uptake. Conclusions Increased carotid plaque inflammation, as measured by FDG uptake on PET, may be a useful marker for identifying patients with symptomatic carotid atherosclerosis who are at risk of recurrence. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to identify clinical factors which may help in predicting the requirement of support of mechanical ventilation (MV) in patients with stroke. This was a prospective cohort study done at a tertiary referral center of India, from December 2008 to December 2009. All consecutive patients of acute stroke, who were admitted from emergency or through outpatient department, and were ≥18years and in whom written consent was available, were considered for the study. Of 193 patients included in the study, 60 (31.08%) patients were intubated due to various reasons. Multivariate analysis of statistically significant and most clinically important variables showed that overall predictor accuracy of requirement of mechanical ventilation is 88% if patients had history of progression of symptoms (OR=10.38; p<0.001), loss of consciousness at the time of onset (OR=3.18; p=0.011) and GCS motor score ≤5 (p

Abstract: Background: Stroke vascular territories may influence response to thrombolysis, although supporting data are limited. The aim of the study was to test the hypothesis that the current available prediction scores might inaccurately estimate the risk of symptomatic intracerebral hemorrhage (SICH) after intravenous thrombolysis in patients with posterior circulation stroke. Methods: We applied the Safe Implementation of Thrombolysis in Stroke (SITS) SICH risk score to data from four hospital-based stroke registries. Patients were grouped according to anterior or posterior circulation stroke. The main outcome measure was SICH per various definitions. Performance of the risk score was assessed with the c statistic. Results: Data of 518 thrombolyzed patients (434 anterior, 84 posterior) were studied. The overall rate of SICH varied from 3.5% to 6.9% depending on the SICH definition. Patients with posterior circulation stroke were less likely to have post-thrombolysis SICH per NINDS (P=0.042), per ECASS II (P=0.013), or any ICH (P=0.001), and their rate of SICH was markedly lower than predicted (1.2% versus 7.1% by the NINDS definition; 0% versus 4.8%, ECASS II; 0% versus 1.6%, SITS-MOST). The SITS SICH risk score shows moderate model discrimination across the SICH definitions, with c statistic ranging from 0.64 to 0.70. Conclusions: The risk of SICH after intravenous thrombolysis in patients with posterior circulation stroke was low enough to render the SITS SICH risk score or other similar prediction models unnecessary. Awareness of stroke territory might help clinicians judiciously use the risk assessment models. [Copyright &y& Elsevier]

Abstract: Background: Renal dysfunction is associated with poor outcomes in ischaemic stroke but remains unproven post intravenous thrombolysis. We studied the renal function in stroke patients treated with intravenous tissue plasminogen activator (IV tPA). Methods: We retrospectively analysed consecutive ischaemic stroke patients treated with IV tPA (0.9mg/kg) from January 2003 to December 2011. Collected data included demographics, medical histories, stroke severity measured by National Institutes of Health Stroke Scale (NIHSS), serum urea, creatinine, estimated glomerular filtration rate (eGFR), platelet, white cell count and international normalised ratio (INR) at baseline. Poor clinical outcome was defined as modified Rankin Scale (mRS) of 2 to 6 at 3months. Logistic regression analysis was performed to test the association between renal function and clinical outcomes adjusted for confounders. Results: In the 378 patients included, the median age was 72 (IQR=62–81) years, 54.2% were male. Median baseline NIHSS was 12 (IQR=8–18). There was a statistically significant association between all three renal function markers. After adjustments for confounding factors, baseline urea was significantly associated with poor outcome (OR=1.100; 95% CI 1.010–1.198permmol/L; p=0.028) and mortality (OR=1.117; 95% CI 1.027–1.213permmol/L; p=0.009), eGFR was associated with mortality (OR=0.984; 95% CI 0.970–0.998permL/min/1.73m2; p=0.026) but not poor outcome (OR=0.994; 95% CI 0.983–1.004permL/min/1.73m2; p=0.230), and serum creatinine was not significant for poor outcome (OR=1.037; 95% CI 0.967–1.113per10μmol/L; p=0.306) or mortality (OR=1.032; 95% CI 0.979–1.088per10μmol/L; p=0.238). No association was observed between ICH and any renal function test. Conclusions: Elevated serum urea was independently associated with poor clinical outcome and mortality in acute ischaemic stroke patients treated with IV tPA. [Copyright &y& Elsevier]

Abstract: Objective: We aimed to explore the association between abnormal glucose metabolism such as diabetes, prediabetes, and short-term prognosis in patients with acute ischemic stroke. Methods: Of 242 consecutive acute ischemic stroke patients, a 75-g oral glucose tolerance test was administered to 116 patients without previously diagnosed diabetes. One hundred forty patients were classified into diabetes, 52 patients were prediabetes (impaired glucose tolerance or impaired fasting glucose or both), and 50 patients were normal glucose tolerance (NGT). The association between each glycemic status and early neurological deterioration (END; increase in the NIH Stroke Scale (NIHSS) of ≥2 points during the first 14days after admission) or poor short-term outcome (30-day modified Ranking Scale [mRS] score 2–6) was evaluated. Results: In multivariable analysis, the risk of END was significantly higher in the diabetes group than in the NGT group (ORs=11.354; 95% CI, 1.492–86.415; p=0.019), even after adjustment for possible confounding factors (ORs=12.769; 95% CI, 1.361–119.763; p=0.026). Similar but insignificant associations were observed between prediabetes and NGT groups (ORs=6.369; 95% CI, 0.735–55.177; p=0.093). The risk of poor outcome (30-day mRS 2–6) was significantly higher in the diabetes group (ORs=3.667; 95% CI, 1.834–7.334; p<0.001) than in the NGT group, even after adjusting for confounding factors (ORs=3.340; 95% CI, 1.361–8.195; p=0.008). Similar but insignificant associations were observed between prediabetes and NGT groups (ORs=2.058; 95% CI, 0.916–4.623; p=0.08). Conclusion: In our patient population, both diabetes and prediabetes were associated with a poor early prognosis after acute ischemic stroke. [Copyright &y& Elsevier]

Abstract: Background: We aimed to devise a scale comprising a simple multiplication of initial National Institutes of Health Stroke Scale (NIHSS) score and onset-to-treatment time (OTT) as a scale for predicting outcomes after recombinant tissue plasminogen activator (rt-PA) therapy. Methods: Data from rt-PA patients in 10 stroke centers in Japan were investigated. NIHSS-time score was calculated as initial NIHSS score×OTT. Results: Subjects comprised 526 patients. Median NIHSS score was 12 (7–18), and median OTT was 2.42h (2.00–2.75h). Median NIHSS-time score was 27.7 (16.9–41.7). Good (modified Rankin Scale [mRS] 0–1) and poor (mRS 4–6) outcome rates at 3months for patients with NIHSS-time scores ≤10 were 71.1% and 7.8%, compared to 54.7% and 16.5% for scores >10 and ≤20, 38.9% and 31.9% for scores >20 and ≤30, 25.0% and 44.6% for scores >30 and ≤40, and 17.4% and 61.8% for scores >40, respectively. Cut-off NIHSS-time scores to predict good and poor outcomes with 50% probability were defined as 20 and 40, respectively. Multivariate logistic regression analysis revealed NIHSS-time score as an independent predictor of good (odds ratio [OR], 0.587; 95% confidence interval [CI], 0.422–0.818, p=0.002) and poor (OR, 1.756; 95%CI, 1.227–2.514, p=0.002) outcomes after adjusting for age, sex, NIHSS score, OTT, Alberta Stroke Program Early CT Score, internal carotid artery occlusion, and glucose level. Conclusions: NIHSS-time score predicts clinical outcomes in rt-PA patients. [Copyright &y& Elsevier]

Abstract: Background and purpose: Patients with severe acute stroke are at high risk for systemic infections which are associated with an increase in morbidity and mortality; nevertheless current guidelines do not recommend prophylactic antibiotic therapy. Sensitive detection of pathogens in the blood is desirable to guide early antibiotic therapy. We studied the yield of blood culture testing and microbiological PCR-based methods for early detection of post-stroke bacteremia. Methods: Serial blood culture tests either during the first fever episode (>38.5°C) or 24h after admission were performed every 12h for up to 96h after admission. Additionally, microbiological PCR-based techniques for the detection of microbiological pathogens were performed once during the first fever episode prior to initiating antibiotic treatment. Results: 21 severely affected acute stroke patients deemed at high risk for systemic infections (median (interquartile range (IQR)) at admission NIHSSS 19 (15–30) were enrolled; 20 patients were intubated within 5h after ICU admission. All patients developed clinical signs and laboratory constellations compatible with systemic infections within 36h after admission. However, no patient had pathogenic bacteria either in serial blood culture analyses during the first 96h after admission or by PCR-based techniques. Conclusions: Very early bacteremia seems not to be a feature of severe stroke in patients despite signs of early immune system depression and frequent subsequent evidence of infection including pneumonia. Consequently our data suggests, that routine early blood-based standard or molecular microbiological assays do not reveal bacteremia, this finding questions the usefulness of their routine performance in this context. [Copyright &y& Elsevier]

Abstract: Background: Ischemic lesion growth may be a surrogate marker of clinical outcome, but no such interrelationship after thrombolysis has yet been determined. We evaluated the association between early infarct growth on diffusion-weighted imaging (DWI) and long-term clinical outcome after thrombolysis. Methods: We retrospectively reviewed outcomes in patients with acute middle cerebral artery territory stroke who had been treated with intravenous tissue plasminogen activator or intra-arterial urokinase. DWI lesion volumes were measured at baseline and within 7days, and the difference was calculated. Clinical outcome was evaluated using the modified Rankin Scale (mRS) at 3months. Good and poor clinical outcomes were defined as: a) mRS 0–1 vs. mRS 2–6, b) mRS 0–2 vs. mRS 3–6, and c) responder analysis which was influenced by the baseline National Institutes of Health Stroke Scale (NIHSS) scores: good and poor outcomes were defined as mRS 0 vs. mRS 1–6 if the baseline NIHSS score was <8, mRS 0–1 vs. mRS 2–6 if the NIHSS score was 8–14, and mRS 0–2 vs. mRS 3–6 if the NIHSS score was >14. The relationship between the ischemic lesion volume change and clinical outcome was explored. The cut-off value of infarct growth predicting long-term outcome was estimated using receiver operating characteristic analysis. Results: Of the 81 patients included, 67 (82.7%) showed lesion growth, and absolute growth was significantly related to poor outcomes (P<0.001 all for mRS 2–6, mRS 3–6, and responder analysis). Multivariate analysis showed that absolute lesion growth was an independent predictor of poor outcome, defined as mRS 2–6 (P=0.002; odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02–1.10), mRS 3–6 (P=0.001; OR, 1.06; 95% CI, 1.02–1.10), and poor outcome by responder analysis (P=0.001; OR, 1.06; 95% CI, 1.03–1.10). The cut-off values of lesion growth that discriminated between good and poor outcomes were 14.11cm3 for mRS 2–6; 15.87cm3 for mRS 3–6; and 14.11cm3 in responder analysis. Conclusions: Early DWI lesion growth is an independent predictor of poor outcome after thrombolysis and may serve a potential surrogate marker of clinical outcome in acute stroke trials. [Copyright &y& Elsevier]

Abstract: Purpose: A nationwide survey was conducted regarding anticoagulant therapy in patients with acute intracerebral hemorrhage (ICH) on warfarin with nonvalvular atrial fibrillation (NVAF). Methods: A questionnaire on standard therapeutic strategy for warfarin-related ICH in patients with NVAF was mailed to 416 institutes. Results: A total of 329 physicians (79%) responded with a completed questionnaire. On admission, all respondents stopped warfarin medication and 94% normalized the international normalized ratio (INR) mainly by Vitamin K (63%), followed by fresh frozen plasma (20%), and prothrombin complex concentrate (10%). Afterwards, 91% of the respondents restarted anticoagulation and 3% used antiplatelet for prevention of thromboembolism, but the remaining 6% disagreed with restarting antithrombotic therapy. As contraindications for resuming anticoagulation, recurrent ICH (59%) and poor functional condition (59%) were often chosen. Of those who restarted anticoagulation, the timing was within 4days in 7%, 5 to 7days in 21%, 8 to 14days in 25%, 15 to 28days in 28% and 29days or later in 18%. The major key finding on follow-up CT to restart anticoagulation was the absorption tendency of hematomas (47%). When restarting anticoagulation, 76% of the respondents used warfarin alone and 20% used either unfractionated heparin plus warfarin or heparin alone. Conclusion: A large majority of respondents responsible for ICH management stopped oral warfarin medication and normalized INR on admission, and restarted anticoagulation after acute ICH in patients with NVAF. However, the strategies to normalize INR and to restart anticoagulant therapy varied greatly and depended on each individual physician''s decision. [Copyright &y& Elsevier]

Abstract: Background and purpose: The etiologic diagnosis of intracranial arterial occlusion is sometimes challenging because of the dynamic nature of acute stroke. We investigated whether short-term follow-up vascular imaging adds additional information to the differential diagnosis between intracranial atherosclerotic and embolic occlusion. Methods: Acute ischemic stroke patients with symptomatic middle cerebral artery (MCA) occlusion on MR angiography (MRA) within 24h of symptom onset were included. Follow-up MRA was performed 5–7days after stroke onset. Stroke subtypes were independently determined at baseline and follow-up MRAs based on clinical, laboratory and imaging findings. Results: In the 108 included patients, the most common etiologic subtype of initial stroke was intracranial large artery atherosclerosis (ICLAA) in 70 patients, followed by cardioembolism in 29 and other causes in 9. On follow-up MRA, 32 (29.6%) patients showed either significant or complete recanalization. Of these, 10 had been originally diagnosed with ICLAA, but were reclassified as a cryptogenic mechanism after follow-up MRA. Multiple logistic regression analysis showed that the presence of coexisting arterial atherosclerosis (odds ratio [OR], 6.91; 95% confidence interval [CI], 2.67–17.91; p<0.001); the absence of large territorial infarction (OR, 4.06; 95% CI, 1.39–11.85; p=0.010); and smoking (OR, 2.54; 95% CI, 1.028–6.29; p=0.043) were significantly associated with a final diagnosis of ICLAA. Conclusion: In the absence of follow-up vascular imaging, a substantial proportion of patients with intracranial middle cerebral arterial occlusion may be misdiagnosed as ICLAA. Evaluation of early dynamic changes in intracranial middle cerebral arterial occlusion may provide useful information for the differential diagnosis of intrinsic atherosclerosis and embolic occlusion. [Copyright &y& Elsevier]

Abstract: Objective: Readmission is an important indicator for the quality of healthcare services. The authors examined the reasons for 30-day readmission among urban stroke patients, and their clinical consequences. Methods: Consecutive patients admitted to a JCAHO certified primary stroke center with ischemic stroke or transient ischemic attacks (TIA) were included. Demographics, TOAST mechanism, risk factors, treatments administered and discharge destination were collected. Charts were reviewed for readmissions up to 30days from discharge. Reasons for readmission and outcomes in terms of disability and discharge destination were determined. Results: Two hundred sixty-five patients (50.9% male; 79.6%African American; mean age 60.9years) were included. There were 205(77.4%) strokes and 60(22.6%) TIAs. Thirteen (5%) patients died during their first admission. Of the remaining 252 patients, 25 (9.9%) were readmitted within 30days. The reason for readmission was neurological in 8/25 patients (32%; 3 ischemic strokes, 1 hemorrhagic stroke and 4 TIAs); and non-neurological in 17/25 patients (68%). The frequent non-neurological reasons were infections (6/25), electrolyte disturbances (3/25) and trauma related to falls (2/25). Patients with coronary artery disease were more likely to be readmitted (45.5% vs. 14.7%; p=0.001) An NIH stroke scale ≥10 predicted readmission (50.0% vs. 25.4% for NIHSS <10; p value 0.02). Patients discharged home or to acute rehabilitation units were less likely to be readmitted than those discharged to subacute rehabilitation units or nursing homes (8.2% vs. 23.8%; p value=0.01). Interpretation: Disabling strokes are more likely to be readmitted. The reason is often non-neurological, and sometimes preventable. Physicians should review cases that return within 30days and determine best practices that prevent readmission. [Copyright &y& Elsevier]

Abstract: Purpose: The aim of this study was to examine whether CHADS2 score is associated with clinical outcomes following recombinant tissue type plasminogen activator (rt-PA) therapy in stroke patients with atrial fibrillation (AF). Methods: We studied 218 consecutive stroke patients with AF [126 men, mean age 74.2 (SD 9.6) years] who received intravenous rt-PA therapy. CHADS2 score was calculated as follows: 2 points for prior ischemic stroke and 1 point for each of the following: age≥75years, hypertension, diabetes, and congestive heart failure. Results: Congestive heart failure was documented in 23 patients, hypertension in 138, age≥75years in 116, diabetes in 35, and prior stroke in 35. The distribution of each CHADS2 score was: score of 0, 16.1% of patients; 1, 30.3%; 2, 29.4%; and 3 to 5, 24.3%. The median initial NIHSS score for each CHADS2 category was 12 (IQR 8–17), 16 (10–20), 14.5 (10–20.75), and 16 (11–21), respectively (p =0.168). Symptomatic ICH within the initial 36h was found in 2.9%, 4.6%, 6.3%, and 0% of patients with each CHADS2 category, respectively. Cardiovascular events within 3months occurred in 0%, 0%, 7.8% and 5.7%, respectively. Percentage of patients with chronic independence at 3months corresponding to modified Rankin Scale≤2 was 57.1%, 45.5%, 31.3%, and 28.3%, respectively. Adjusted CHADS2 score was inversely associated with chronic independence (OR 0.72, 95% CI 0.55–0.93). Conclusion: Lower CHADS2 score was associated with chronic independence at 3months after intravenous rt-PA therapy in stroke patients with AF. [Copyright &y& Elsevier]

Abstract: Background and purpose: Detection rate of right-to-left shunt (RLS) may be lower in stroke patients with atrial fibrillation (AF) than in those without AF. This may be due to the mechanism of embolic stroke in AF patients that involves cardiac embolus rather than paradoxical embolism due to RLS. Patients with AF frequently have subclinical heart failure, resulting in elevated left atrial (LA) pressure, which may prevent opening of a patent foramen ovale (PFO). We aimed to investigate whether the detection rate of RLS in stroke patients with AF was affected by elevated LA pressure. Method: We enrolled consecutive acute stroke patients with AF and, as controls, consecutive acute stroke patients without AF. RLS was diagnosed using contrast transcranial Doppler. To assess LA pressure, the ratio of early mitral inflow velocity to diastolic mitral annular velocity (E/E′) was measured using transthoracic echocardiography. Result: We enrolled 171 patients with AF (AF group, age, 78years [IQR, 70–83]) and 171 patients without AF (control group, age, 73years [IQR, 64–81]). RLS was observed less frequently in AF patients than in the control group (9% vs. 18%, p=0.024). E/E′ ratio was higher in AF patients (13.1 [9.4–17.4] vs. 10.9 [8.2–13.7], p<0.001). Among controls, E/E′ ratio did not differ between patients with and without RLS (11.8 [8.5–12.9] vs. 10.8 [8.0–13.9], p=0.884). Conversely, in AF patients, E/E′ ratio was lower in patients with RLS than in those without RLS (9.0 [8.3–12.6] vs. 13.6 [10.2–18.1], p=0.008). Multivariate regression analysis demonstrated that E/E′ ratio of <11.0 was an independently associated with RLS (OR 4.61, 95%CI 1.21–17.62, p=0.025). Result: RLS was detected less frequently in AF patients than in controls. Elevated LA pressure was associated with the absence of RLS in AF stroke patients and may prevent opening of a PFO. [Copyright &y& Elsevier]

Abstract: Background and purpose: The present study investigated the relationship between serial changes in ischemic lesion volume (ILV) and neurological recovery after t-PA therapy. Methods: A total of 110 consecutive patients with ICA and MCA occlusion on MRA treated with t-PA within 3h of onset were prospectively studied. MRI including MRA, DWI, and FLAIR, was performed before, 1h, 24h, and 7days after t-PA infusion to measure serial changes in ILV. Results: The mean (SD) values of ILV at baseline, 1h, 24h, and 7days after t-PA infusion were 30.2 (61.0), 48.1 (76.3), 98.3 (125.3), and 125.9 (149.8) cm3, respectively. Recovery at 7days was remarkable in 46 patients and good in 21 patients. Change in NIHSS score (baseline NIHSS minus NIHSS at 7days) correlated with ΔILV (ILV at 7days minus baseline ILV) (r =0.611, P <0.0001). Sensitivity and specificity curve analysis demonstrated that a cutoff value for ΔILV of 40cm3 (sensitivity, 80.0%; specificity, 79.3%) indicated remarkable recovery, and that 80cm3 (78.8% and 76.3%) indicated good recovery. Conclusion: The thresholds of ΔILV enlargement for remarkable and good recovery after t-PA therapy were 40 and 80cm3, respectively. [Copyright &y& Elsevier]

Abstract: We examined the association between plasma adiponectin (ADPN) levels and cardiovascular mortality in acute stroke patients. We enrolled 552 consecutive acute stroke patients. Measurements were made at baseline and the patients were followed prospectively. The primary endpoint was cardiovascular (stroke or ischemic heart disease) death and the secondary endpoint was all-cause death. During the median follow-up period of 17months, 39 patients died, 15 being due to stroke. No patients died of ischemic heart disease. After adjustment for age, sex, presence of hypertension, diabetes mellitus, and hyperlipidemia, the highest tertile of ADPN level (>11.7μg/ml) was associated with stroke mortality (hazard ratio: 6.55, 95% confidence interval: 1.73–24.8), but not with all-cause mortality (hazard ratio: 1.89, 95% confidence interval: 0.95–3.77). High levels of plasma ADPN can be a predictor of stroke mortality during the 17months following an episode of acute stroke in patients. [Copyright &y& Elsevier]

Abstract: Purpose: Time from stroke onset to treatment (OTT) is potentially an important factor affecting subsequent outcome in patients treated with t-PA. The aim of the study was to assess the correlation between OTT and early recanalization rate after IV-t-PA therapy. Methods: Consecutive stroke patients treated with t-PA within 3h of onset were prospectively studied. Patients with major brain artery occlusion on MRA before t-PA infusion were enrolled. The correlation between OTT and the early recanalization rate within 1h after t-PA infusion was determined. Results: 102 patients (M1 occlusion, 41 patients; M2, 19; ICA, 31; BA, 8; and PCA, 3) were enrolled. Follow-up MRA within 1h after t-PA infusion showed early recanalization in 42 (41.2%) patients (complete in 13 patients, partial in 29). The early recanalization rate was 53.8% with OTT ≤100min, 57.1% in 101–110min, 50.0% in 111–120min, 63.6% in 121–130min, 33.3% in 131–140min, 30.0% in 141–150min, 36.4% in 151–160min, 18.2% in 161–170min, and 32.0% in 171–180min. OTT was negatively correlated with the early recanalization rate (r =−0.767, P =0.0301). After adjusting the presence of age (>74), ICA occlusion, baseline NIHSS score (<10), and glucose (>150mg/dl), adjusted OR for early recanalization of OTT ≤130min against OTT >130–180min was 2.97 (95% CI 1.27–6.96, P =0.012). Conclusion: Early recanalization depended on time from stroke onset to IV-t-PA administration. Thus, t-PA should be given to acute stroke patients as soon as possible. [Copyright &y& Elsevier]

Abstract: In modern medicine brain imaging is an essential prerequisite not only to acute stroke triage but also to determining the specific therapy indicated. This article reviews the need for imaging the brain in acute stroke, penumbral pathophysiology, penumbral imaging techniques, as well as current status of various imaging modalities that are being employed to select patients for specific therapeutic approaches. [Copyright &y& Elsevier]

Abstract: A secreted isoform of the receptor for advanced glycation end products (RAGE), soluble RAGE (sRAGE), can neutralize the adverse effects of RAGE signaling by acting as a decoy. RAGE signaling contributes to the development of diabetic microangiopathy, however few studies have addressed pivotal roles of RAGE signaling in acute stroke. We examined plasma sRAGE levels associated with clinical features in acute stroke patients. Plasma sRAGE was measured in 482 patients (318 men; mean age 71years) admitted within three days of stroke onset. Median values of sRAGE were significantly different among stroke subtypes (p =0.001); 1010pg/ml in atherothrombotic infarction, 933pg/ml in lacunar, 1280pg/ml in cardioembolic infarction, 1050pg/ml in other types of infarctions, and 943pg/ml in primary intracerebral hemorrhage. Severe leukoaraiosis on brain MR images, high NIHSS scores on admission, cigarette smoking, and normal estimated glomerular filtration rate were significantly associated with low sRAGE levels (p <0.05). The low level of sRAGE was associated with severe leukoaraiosis, reflecting long-standing presence of hypertensive angiopathy. Kidneys play a role in the removal of sRAGE. RAGE signaling can contribute to the deterioration of neuronal damage under severe leukoaraiosis, result in a high NIHSS score on admission in acute stroke patients, especially those with smoking habits. [Copyright &y& Elsevier]

Abstract: Background and purpose: The intravenous t-PA thrombolysis is not thought to be effective in most patients with internal carotid artery (ICA) occlusion. However, we have sometimes observed dramatic recovery in patients with ICA occlusion after t-PA therapy. The aim of the present study was to investigate the mechanism of dramatic recovery in such patients. Methods: Consecutive ICA occlusion patients treated with t-PA were prospectively studied. MRI, including MRA, was performed before and within 1 h and 24 h after t-PA thrombolysis. Patients were divided into 2 groups: dramatic recovery (D group) and non-dramatic recovery (ND group). Results: The subjects consisted of 21 consecutive stroke patients (14 males; mean age, 76.5±8.4 years). Six (28.6%) patients (D group) had dramatic improvement and 15 (71.4%) patients (ND group) did not. The frequency of partial or complete recanalization within 1 h and 24 h after t-PA infusion was 14.3% and 50.0% for the ICA, 9.5% and 40.0% for the MCA, and 23.8% and 65.0% for the ICA or MCA, respectively. There was no difference in the frequency of ICA recanalization 24 h after t-PA infusion between the 2 groups (66.7% for D group vs. 42.9% for ND group, P =0.629); however, MCA recanalization was more frequent in the D group than in the ND group (100.0% vs. 14.3%, P =0.0004). Conclusion: Recanalization of the MCA, which provides collateral flow, appears to play an important role in dramatic recovery after t-PA therapy in patients with ICA occlusion. [Copyright &y& Elsevier]

Abstract: Introduction: Baseline severity and clinical stroke syndrome (Oxford Community Stroke Project, OCSP) classification are predictors of outcome in stroke. We used data from the ‘Tinzaparin in Acute Ischaemic Stroke Trial’ (TAIST) to assess the relationship between stroke severity, early recovery, outcome and OCSP syndrome. Methods: TAIST was a randomised controlled trial assessing the safety and efficacy of tinzaparin versus aspirin in 1484 patients with acute ischaemic stroke. Severity was measured as the Scandinavian Neurological Stroke Scale (SNSS) at baseline and days 4, 7 and 10, and baseline OCSP clinical classification recorded: total anterior circulation infarct (TACI), partial anterior circulation infarct (PACI), lacunar infarct (LACI) and posterior circulation infarction (POCI). Recovery was calculated as change in SNSS from baseline at day 4 and 10. The relationship between stroke syndrome and SNSS at days 4 and 10, and outcome (modified Rankin Scale at 90 days) were assessed. Results: Stroke severity was significantly different between TACI (most severe) and LACI (mildest) at all four time points (p <0.001), with no difference between PACI and POCI. The largest change in SNSS score occurred between baseline and day 4; improvement was least in TACI (median 2 units), compared to other groups (median 3 units) (p <0.001). If SNSS did not improve by day 4, then early recovery and late functional outcome tended to be limited irrespective of clinical syndrome (SNSS, baseline: 31, day 10: 32; mRS, day 90: 4); patients who recovered early tended to continue to improve and had better functional outcome irrespective of syndrome (SNSS, baseline: 35, day 10: 50; mRS, day 90: 2). Conclusions: Although functional outcome is related to baseline clinical syndrome (best with LACI, worst with TACI), patients who improve early have a more favourable functional outcome, irrespective of their OCSP syndrome. Hence, patients with a TACI syndrome may still achieve a reasonable outcome if early recovery occurs. [Copyright &y& Elsevier]