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Introduction: Many guidelines now recommend early rehabilitation for acute stroke patients. However, evidence remains lacking regarding the specific timings for initiation of various rehabilitation steps and management when complications are encountered in acute stroke rehabilitation. This survey aimed to investigate actual clinical situations in acute stroke rehabilitation in Japan and to improve the medical systems for rehabilitation and plan further studies. Methods: This nationwide, cross-sectional, web-based questionnaire survey was administered between February 7, 2022, and April 21, 2022, targeting all primary stroke centers (PSCs) in Japan. Among several components of the survey, this paper focused on the timing of the initiation of three rehabilitation steps (passive bed exercise; head elevation; and out-of-bed mobilization), along with the management of rehabilitation (continued or suspended) in the event of complications during acute stroke rehabilitation. We also investigated the influence of facility features on these contents. Results: Responses were obtained from 639 of the 959 PSCs surveyed (response rate: 66.6%). In cases of ischemic stroke and intracerebral hemorrhage, most PSCs initiated passive bed exercise on day 1, head elevation on day 1, and out-of-bed mobilization on day 2 (with day of admission defined as day 1). In cases with subarachnoid hemorrhage, rehabilitation steps were delayed compared to other stroke subtypes or showed wide variation depending on the facility. Passive bed exercise was accelerated by the presence of protocols for rehabilitation and weekend rehabilitation. Out-of-bed mobilization was accelerated by the presence of a stroke care unit. Facilities with board-certified rehabilitation doctors were cautious regarding the initiation of head elevation. Most PSCs suspended rehabilitation training in the event of symptomatic systemic/neurological complications. Conclusion: Our survey revealed the actual situation of acute stroke rehabilitation in Japan and indicated that some facility features appear to influence early increases in physical activity levels and early mobilization. Our survey provides fundamental data to improve the medical systems for acute stroke rehabilitation in the future. [ABSTRACT FROM AUTHOR]

Background: The Hunter area in New South Wales, Australia, is a well-defined geographical area with a population of 578,486 (2006). This paper presents trends from 1996 to 2008 for prospectively registered hospital admissions of adults aged 20 years and above with acute stroke. Method: Crude, age-standardised and age-specific stroke attack rates per 100,000 population and case fatality rates at standard time points were calculated. A medical record audit of stroke and stroke mimics was undertaken to determine discharge coding accuracy. Results: 9,796 acute stroke events were registered among 8,830 individuals at 14 public acute hospitals. Crude and age-standardised attack rates decreased consistently from 1996 to 2008. Crude rates fell from 184 to 176 per 100,000 population and age-standardised rates from 129 to 106 per 100,000 (attack rate reduction of 0.85% per year, p = 0.027; and 2.38% per year, p < 0.001, respectively). Annual attack rates for females were on average 27.70% (p < 0.001) lower than for males. Age-specific rates fell for each age bracket between 45 and 74 years. Case fatality rates remained constant. There was a 97.5% proportion of agreement between audit and coding. Conclusion: This study demonstrates falling stroke attack rates but stable case fatality over 13 years in a mixed urban and rural population of New South Wales, Australia. It suggests benefits from cardio- and cerebrovascular prevention strategies; however, it also indicates that stroke remains a major disease burden in this region. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The Los Angeles Motor Scale (LAMS) is a 3-item, 0-to-5-point motor stroke-deficit scale derived from the Los Angeles Prehospital Stroke Screen. We assessed the predictive validity (for interventions performed and discharge disposition) of the LAMS performed in the field by paramedics in a geographic region of over 5,200 km2, covering both rural and urban areas. Methods: We analyzed data gathered from Phase I of the LIT-PASS study (Large Vessel Occlusion Identification Through Prehospital Administration of Stroke Scales) which included all patients with suspected acute cerebrovascular disease, as assessed by the Balance, Eyes, Face, Arm, Speech, Terrible Headache/Time to Call 911 (BE-FAST) test. Results: Among 1,906 patients with median age 72 years (interquartile range [IQR] 60–81), 53% were female with a median on-scene time of 15 min (IQR 12–19). C statistics for the interventions of mechanical thrombectomy, alteplase administration, computed tomography angiography, and perfusion imaging were 0.681, 0.643, and 0.680, respectively. The cut point for predicting these 3 interventions was confirmed to be LAMS ≥ 4. LAMS ≥ 4 had sensitivity 0.730 (0.661–0.790) and specificity 0.570 (0.539–0.601) for mechanical intervention (endovascular thrombectomy, coiling, or clipping) and relative risk of 2.98 (2.19–4.07) for in-hospital death. Conclusions: This real-world field study validates the LAMS as an effective tool for prehospital assessment of suspected strokes in determining transport decisions, with predictive validity for interventions performed. [ABSTRACT FROM AUTHOR]

Background and Aims: Syphilis and stroke are high prevalent diseases in south Brazil and estimates of concomitance and possible role of syphilis in acute stroke are lacking. Our aims are to estimate the prevalence of syphilis and neurosyphilis (NS) in a cohort of tertiary stroke center. Methods: We reviewed all hospital records of stroke/transitory ischemic attack (TIA) using International Classification of Diseases, 10th revision, at discharge, frequency of syphilis screen, serology positivity, cerebrospinal fluid (CSF) analysis, and prevalence of NS in this stroke population applying CDC criteria. Results: Between 2015 and 2016, there were 1,436 discharges for cerebrovascular events and in 78% (1,119) of these cases, some syphilis screening was performed. We have found a frequency of positive serology for syphilis of 13% (143/1,119), and higher stroke severity was the main determinant for non-screening. Applying standard NS criteria, 4.7% (53/1,119) cases with CSF analysis had NS diagnosis: 8 based on CSF-Venereal Disease Research Laboratory (VDRL) positive and 45 based on abnormal CSF white cells or protein, but CSF VDRL negative. NS VDRL positive cases were younger, had higher serum VDRL title, had more frequent HIV infection, and received NS treatment more often. Demographic and clinical characteristics were not different between NS VDRL negative and non-NS cases. Conclusion: Positive syphilis serology is frequent in patients with acute stroke/TIA in our region. Acute post-stroke CSF abnormalities make the diagnosis of NS difficult in the context of CSF VDRL negative. [ABSTRACT FROM AUTHOR]

Background and Purpose: MLC601 has been shown in preclinical studies to enhance neurorestorative mechanisms after stroke. The aim of this post hoc analysis was to assess whether combining MLC601 and rehabilitation has an effect on improving functional outcomes after stroke. Methods: Data from the CHInese Medicine NeuroAiD Efficacy on Stroke (CHIMES) and CHIMES-Extension (CHIMES-E) studies were analyzed. CHIMES-E was a 24-month follow-up study of subjects included in CHIMES, a multi-centre, double-blind placebo-controlled trial which randomized subjects with acute ischemic stroke, to either MLC601 or placebo for 3 months in addition to standard stroke treatment and rehabilitation. Subjects were stratified according to whether they received or did not receive persistent rehabilitation up to month (M)3 (non- randomized allocation) and by treatment group. The modified Rankin Scale (mRS) and Barthel Index were assessed at month (M) 3, M6, M12, M18, and M24. Results: Of 880 subjects in CHIMES-E, data on rehabilitation at M3 were available in 807 (91.7%, mean age 61.8 ± 11.3 years, 36% female). After adjusting for prognostic factors of poor outcome (age, sex, pre-stroke mRS, baseline National Institute of Health Stroke Scale, and stroke onset-to-study-treatment time), subjects who received persistent rehabilitation showed consistently higher treatment effect in favor of MLC601 for all time points on mRS 0–1 dichotomy analysis (ORs 1.85 at M3, 2.18 at M6, 2.42 at M12, 1.94 at M18, 1.87 at M24), mRS ordinal analysis (ORs 1.37 at M3, 1.40 at M6, 1.53 at M12, 1.50 at M18, 1.38 at M24), and BI ≥95 dichotomy analysis (ORs 1.39 at M3, 1.95 at M6, 1.56 at M12, 1.56 at M18, 1.46 at M24) compared to those who did not receive persistent rehabilitation. Conclusions: More subjects on MLC601 improved to functional independence compared to placebo among subjects receiving persistent rehabilitation up to M3. The larger treatment effect of MLC601 was sustained over 2 years which supports the hypothesis that MLC601 combined with rehabilitation might have beneficial and sustained effects on neuro-repair processes after stroke. There is a need for more data on the effect of combining rehabilitation programs with stroke recovery treatments. [ABSTRACT FROM AUTHOR]

Background: This study assessed the incidence and predictors of short-term stroke recurrence in ischemic stroke patients with active cancer, and elucidated whether cancer-associated hypercoagulation is related to early recurrent stroke. Methods: We retrospectively enrolled acute ischemic stroke patients with active cancer admitted to our hospital between 2006 and 2017. Active cancer was defined as diagnosis or treatment for any cancer within 12 months before stroke onset, known recurrent cancer or metastatic disease. The primary clinical outcome was recurrent ischemic stroke within 30 days. Results: One hundred ten acute ischemic stroke patients with active cancer (73 men, age 71.3 ± 10.1 years) were enrolled. Of those, recurrent stroke occurred in 12 patients (11%). When patients with and without recurrent stroke were compared, it was found that those with recurrent stroke had a higher incidence of pancreatic cancer (33 vs. 10%), systemic metastasis (75 vs. 39%), multiple vascular territory infarctions (MVTI; 83 vs. 40%), and higher -D-dimer levels (16.9 vs. 2.9 µg/mL). Multivariable logistic regression analysis showed that each factor mentioned above was not significantly associated with stroke recurrence independently, but high D-dimer (hDD) levels (≥10.4 µg/mL) and MVTI together were significantly associated with stroke recurrence (OR 6.20, 95% CI 1.42–30.7, p = 0.015). Conclusions: Ischemic stroke patients with active cancer faced a high risk of early recurrent stroke. The concurrence of hDD levels (≥10.4 µg/mL) and MVTI was an independent predictor of early recurrent stroke in active cancer patients. Our findings suggest that cancer-associated hypercoagulation increases the early recurrent stroke risk. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to clarify the incidence, clinical and radiological features and outcomes of isolated posterior inferior cerebellar artery (PICA) dissection in isolated PICA territory infarctions. Methods: We retrospectively reviewed consecutive inpatients with ischemic stroke secondary to isolated PICA dissection from our stroke database between January 2004 and December 2013 and reviewed the literature with regard to those patients. Results: Of 167 consecutive patients with an isolated PICA territory infarction, a total of 10 patients (6.0%, 3 women, 48.1 ± 7.1 years) were diagnosed as having an isolated PICA dissection. Patients with PICA dissection were younger (p < 0.001), more commonly experienced headache at onset (p = 0.008), less commonly had hyperlipidemia (p = 0.044) and showed a lower modified Rankin Scale score at discharge (p = 0.002) when compared with patients without arterial dissection. In 6 of these 10 patients, PICA dissections had not been suspected on initial magnetic resonance angiography (MRA) and were confirmed by follow-up MRA or digital subtraction angiography. In the follow-up period (median 1.5 years, interquartile range 0.5-6.3 years), there were no recurrent ischemic or hemorrhagic stroke events. Conclusions: Isolated PICA dissection as an etiological mechanism in isolated PICA territory infarctions may be more common than was previously recognized to be. The diagnosis of PICA dissection is often difficult and requires close and repeated morphological evaluation. We should carefully identify PICA dissections as a possible cause of PICA territory infarctions. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The global burden of stroke is immense, both in medical and economic terms. With the aging population and the ongoing industrialization of the third world, stroke prevalence is expected to increase and will have a major effect on national health expenditures. Currently, the medical treatment for acute ischemic stroke is limited to intravenous recombinant tissue plasminogen activator (IV r-tPA), but its time dependency leads to low utilization rates in routine clinical practice. Prehospital delay contributes significantly to delayed or missed treatment opportunities in acute stroke. State-of-the-art acute stroke care, starting in the prehospital phase, could thereby reduce the disease burden and its enormous financial costs. Summary: The first part of this review focuses on current education measures for the general public, the emergency medical services (EMS) dispatchers and paramedics. Although much has been expected of these measures to improve stroke care, no major effects on prehospital delay or missed treatment opportunities have been demonstrated over the years. Most interventional studies showed little or no effect on the onset-to-door time, IV r-tPA utilization rates or outcome, except for prenotification of the receiving hospital by the EMS. No data are currently available on the cost-effectiveness of these commonly used measures. In the second part, we discuss new developments for the improvement of prehospital stroke diagnosis and treatment which could open new perspectives in the nearby future. These include the implementation of prehospital telestroke and the deployment of mobile stroke units. These approaches may improve patient care and could serve as a platform for prehospital clinical trials. Other opportunities include the implementation of noninvasive diagnostics (like transcranial ultrasound and blood-borne biomarkers) and the reevaluation of neuroprotective strategies in the prehospital phase. Key Messages: Timely initiation of treatment can effectively reduce the medical and economic burden of stroke and should begin with optimal prehospital stroke care. For this, prehospital telemedicine is a particularly attractive approach because it is a scalable solution that has the potential to rapidly optimize acute stroke care at limited cost. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The aim of the current study was to determine the sensitivity and specificity of CT perfusion (CTP) for the detection of ischemic strokeby performing a systematic review and meta-analysis of published reports. Methods: We searched PubMed, Embase and the Cochrane library using the terms 'perfusion computed tomography', 'ischemic stroke' and synonyms. We included studies that: (1) reported original data, (2) studied the diagnostic value of CTP for detecting ischemic stroke, (3) used MRI-DWI, follow-up MRI or follow-up CT as the reference standard, (4) included at least 10 patients who were suspected of ischemic stroke, and (5) reported the number of true positives, true negatives, false positives and false negatives for the diagnosis of ischemic stroke. Results: Fifteen studies were finally included in the current review with a total of 1,107 patients. A pooled analysis resulted in a sensitivity of 80% (95% confidence interval, CI: 72-86%) and a specificity of 95% (95% CI: 86-98%). Almost two thirds of the false negatives were due to small lacunar infarcts; the remaining false negatives were mostly due to limited coverage. Conclusions: The current systematic review shows that CTP has a high sensitivity and a very high specificity for detecting infarcts. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Diagnosis-related groups (DRGs) are increasingly being used for various purposes in many countries. However, there are no studies comparing different DRG systems in the care of stroke. As part of the EuroDRG project, researchers from 11 countries (i.e. Austria, England, Estonia, Finland, France, Germany, Ireland, the Netherlands, Poland, Sweden and Spain) compared how their DRG systems deal with stroke patients. The study aims to assist clinicians and national authorities to optimize their DRG systems. Methods: National or regional databases were used to identify hospital cases with a diagnosis of stroke. DRG classification algorithms and indicators of resource consumption were compared for those DRGs that individually represent at least 1% of stroke cases. In addition, standardized case vignettes were defined, and quasi prices according to national DRG-based hospital payment systems were ascertained. Results: European DRG systems vary widely: they classify stroke patients according to different sets of variables (between 1 and 7 classification variables) into diverging numbers of DRGs (between 1 and 10 DRGs). In 6 of the countries more than half of the patients are concentrated within a single DRG. The countries' systems also vary with respect to the evaluation of different kinds of stroke patients. The most complex DRG is considered 3.8 times more resource intensive than an index case in Finland. By contrast, in England, the DRG system does not account for complex cases. Comparisons of quasi prices for the case vignettes show that hypothetical payments for the index case amount to only EUR 907 in Poland but to EUR 7,881 in Ireland. Conclusions: Large variations in the classification of stroke patients raise concerns whether all systems rely on the most appropriate classification variables and whether the DRGs adequately reflect differences in the complexity of treating different groups of patients. Learning from other DRG systems may help in improving the national systems. Clinicians and national DRG authorities should consider how other countries' DRG systems classify stroke patients in order to optimize their DRG system and to ensure fair and appropriate reimbursement. In future, quantitative research is needed to verify whether the most important determinants of cost are considered in different patient classification systems, and whether differences between systems reflect country-specific differences in treatment patterns and, most importantly, what influence they have on patient outcomes. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Telemedicine is improving acute stroke care in remote areas. Delay in hospital-to-hospital transfer is a common reason why acute ischemic stroke patients are excluded from interventional therapy. The progressive implementation of these procedures, requiring highly specialized professionals in comprehensive stroke centers, will certainly challenge even more the geographic equity in the access to the best acute stroke treatments. We aimed to assess the benefits of telemedicine in selecting stroke patients for endovascular treatments. Methods: In our Reference Comprehensive Stroke Center (RCSC), we perform urgent intra-arterial procedures in acute stroke patients. Patients may be primarily admitted (PA) or referred from community hospitals with (TMHs; 2 centers) or without telemedicine (nonTMHs; 7 centers). We prospectively studied all consecutive stroke patients undergoing urgent endovascular recanalization procedures in the RCSC. We studied different outcome measures according to the patients' initial admission: PA patients, TMH patients or nonTMH patients. For all patients, demographic and outcome data including serial National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores at 3 months were recorded. Clinical improvement was defined as a decrease ≥4 points on the NIHSS at 7 days or discharge and favorable outcome as mRS ≤2 at 3 months. Whether an endovascular procedure was indicated was decided according to clinical, radiological and transcranial Doppler (TCD) data, independently of the patient's initial admission center. Results: During a 2-year period, 119 patients received endovascular treatment: PA patients 74 (63.1%), TMH patients 25 (20.5%), nonTM patients 20 (16.4%). The mean distance to the RCSC was 52 ± 15 km for TMHs and 34.5 ± 12 km for nonTMHs (p = 0.4). There were no differences in baseline characteristics including age (71, 71.6 and 66.5 years; p = 0.25), baseline NIHSS (18.5, 19 and 18; p = 0.57) and previous use of intravenous tissue plasminogen activator (56.5, 56.5 and 57.9%; p = 0.95). The rate of recanalization (modified Thrombolysis in Cerebral Infarction Score ≥2a) was similar in all groups (75, 66.6 and 68.4%; p = 0.682). TMH and PA patients had similar clinical improvement (61 vs. 63.8%; p = 0.51) and good functional outcome (36.8 vs. 35.3%; p = 0.722). Conversely, nonTMH patients presented a lesser degree of clinical improvement (31.3%) and poorer functional outcome (15.8%) than TMH (p = 0.019 and p = 0.046) and PA patients (p = 0.05 and p = 0.013). TMH patients had significantly shorter door-to-groin puncture times (47 vs. 69 min; p = 0.047). Conclusions: Telemedicine assessment to select patients for endovascular procedures improves the efficiency in stroke management and possibly the early and long-term outcome in patients receiving intra-arterial reperfusion treatment. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Hyperintensity of distal vessels on FLAIR-MRI has been associated with a higher grade of arterial collaterals and a smaller infarct volume in acute stroke patients. No studies analyze the influence of the hyperintense vessel (HV) sign on the speed of the ischemia progression during the first hours. Our aim was to study the association of the HV sign with progression of infarction in acute stroke patients. Methods: From a prospectively derived stroke database, we retrospectively selected acute stroke patients with a large artery occlusion of the anterior circulation admitted to our comprehensive stroke center with available baseline CT scan and a multimodal MRI carried out thereafter to make a decision about endovascular treatment. Progression of the ischemic area was calculated as the difference in the Alberta Stroke Program Early CT Scan (ASPECTS) score between CT scan and diffusion-weighted imaging (DWI). Slow progression was considered as no change or 1 point decrease on the ASPECTS score between both exams. The presence of HV on FLAIR sequence was graded as absent, subtle or prominent by two readers. Results: A total of 70 patients were included in the study. Mean time between baseline CT and MRI was 124 ± 82 min. ASPECTS score on baseline CT was 10 in 34% of patients, 9 in 49% and 8 or less in 17%. ASPECTS score was 2 (1-3) points lower in the DWI and this decrease did not correlate with the time elapsed between the two exams. Distal HV sign was observed in 57/70 (81%) patients (subtle in 33 and prominent in 24). HV was more frequently observed in patients with proximal artery occlusion. There were no differences regarding stroke severity, stroke subtype and ASPECTS score on baseline CT between groups. Patients with prominent HV showed a lower progression of the ischemic area [median ASPECTS score decrease, 1 (1-0)] compared with patients with subtle HV [median ASPECTS score decrease, 2 (2-1)] and patients with absence of HV [median ASPECTS score decrease, 3 (4-3)] (p < 0.001). Prominent HV was independently associated with slow progression of ischemia in a multivariate logistic regression analysis adjusted by systolic blood pressure on admission, site of occlusion and time elapsed between both neuroimaging exams compared to the absence of HV (OR, 16.2; 95% CI, 2.1-123.1) and to subtle HV sign (OR, 6.1; 95% CI, 1.5-23.9). Conclusion: HV sign on FLAIR, especially if prominent, is associated with a slow progression of the ischemic area in acute stroke patients with cerebral artery occlusion of the anterior circulation. This radiological sign may predict the speed of the ischemia progression, opening an opportunity for reperfusion therapies in longer time windows. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Purposes: In a case-control study in patients with acute ischemic stroke and extracranial internal carotid artery (eICA) occlusion, thrombolytic treatment was associated with increased mortality. The aim of this cohort study was to assess the efficacy and safety of thrombolysis in patients with eICA occlusion compared to those without eICA occlusion. Methods: Consecutive patients treated with intravenous tissue-type plasminogen activator within 4.5 h from symptom onset included in the Safe Implementation of Thrombolysis in Stroke - International Stroke Thrombolysis Registry (SITS-ISTR) in 20 Italian centres were analyzed. Acute carotid occlusion was diagnosed using ultrasound examination, angio-CT scan or angio-MRI. Since the SITS-ISTR database did not plan to report the site of vessel occlusion, each participating center provided the code of the patient with eICA occlusion. Patients were divided into 2 groups, those with and those without eICA occlusion. Main outcome measures were: death, disability (modified Rankin Scale, mRS, 3-6) and any intracranial bleeding at 3 months. Multiple logistic regression analysis was performed to reveal predictors for main outcomes. The following variables of interest were included in the analysis: presence of eICA occlusion, age, gender, diabetes mellitus, hyperlipidemia, atrial fibrillation, congestive heart failure, previous stroke, current smoking, antiplatelet treatment at stroke onset, baseline NIHSS score, baseline blood glucose, cholesterol and blood pressure, history of hypertension and stroke onset to treatment time. Results: A total of 1,761 patients without eICA occlusion and 137 with eICA occlusion were included in the study. At 3 months, 42 patients were lost to follow-up (3 with eICA occlusion). Death occurred in 30 (22.4%) patients with eICA occlusion and in 175 (10.2%) patients without (p < 0.0001). Death or disability at 3 months occurred in 91 of 134 patients with eICA occlusion (67.9%) compared with 654 of 1,722 patients without eICA occlusion (37.9%, p < 0.0001). No or minimal disability at 3 months (mRS 0-1) was reported in 25 (18.7%) patients with eICA occlusion and in 829 (48.2%) patients without (p < 0.0001). Any intracranial bleeding detected by CT or MRI at posttreatment imaging was seen in 16 (11.7%) patients with eICA occlusion and in 314 (17.8%) of those without (p = 0.09). The proportion of symptomatic intracerebral hemorrhage was 5.8% for patients with eICA occlusion and 8.0% for patients without (p = 0.16). At logistic regression analysis, eICA occlusion was associated with mortality (odds ratio, OR 5.7; 95% confidence interval, CI 2.9-11.1) and mortality or disability (OR 5.0; 95% CI 2.9-8.7) at 90 days. Conclusions: This cohort study in patients with acute ischemic stroke treated with thrombolysis showed an association between eICA occlusion and adverse outcome. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Purpose: Previous studies have found mortality among ischemic stroke patients to be higher on weekends. We sought to evaluate whether weekend admission was associated with worse outcomes in a large comprehensive stroke center (CSC) cohort. Methods: Consecutive ischemic stroke patients presenting within 6 h of symptom onset were identified using the 8 CSC SPOTRIAS (Specialized Programs of Translational Research in Acute Stroke) database. Patients who received intra-arterial therapy or who were enrolled in a nonobservational clinical trial were excluded. All patients meeting the inclusion criteria were then divided into two groups: weekday admissions or weekend admissions. Weekend admission was defined as Friday 17:01 to Monday 08:59. The remainder were classified as weekday admissions. Multivariate logistic regression was used, adjusting for age, stroke severity on admission [according to the National Institutes of Health Stroke Scale (NIHSS)] and admission glucose, in order to compare the outcomes of the weekend versus the weekday groups. Results: Eight thousand five hundred and eighty-one subjects from the combined SPOTRIAS database were screened from 2002 to 2009; 2,090 (24.4%) of these met the inclusion criteria. There was no significant difference in tissue plasminogen activator treatment rates between the weekday and weekend groups (58.5 vs. 60.4%, p = 0.397). Weekend admission was not a significant independent predictor of inhospital mortality (8.4 vs. 9.9%, p = 0.056), length of stay (4 vs. 5 days, p = 0.442), favorable discharge disposition (38.0 vs. 42.2%, p = 0.122), favorable functional outcome at discharge (41.6 vs. 43.4%, p = 0.805), favorable 90-day functional outcome (54.2 vs. 46.9%, p = 0.301), or 90-day mortality (18.2 vs. 19.8%, p = 0.680) when adjusting for age, NIHSS and admission glucose. Conclusions: In this large cohort of ischemic stroke patients treated at CSCs, we did not observe the 'weekend effect.' This may be due to access to stroke specialists 24 h a day on 365 days a year, nurses with stroke experience and the organized system for delivering care that is available at CSCs. These results suggest that EMS protocol should be reexamined regarding the preferential delivery of weekend stroke victims to hospitals that provide all levels of reperfusion therapy. This further highlights the importance of organized stroke care. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Collateral circulation stabilizes cerebral blood flow in patients with acute occlusion, but its prognostic role is less studied in intracranial atherosclerosis and appears different in moderate to severe stenosis. We aimed to study the associations between antegrade flow across stenosis, collateral flow via leptomeningeal anastomosis, and the neurological outcome and recurrence risk in patients with symptomatic intracranial stenosis. Methods: We examined a cohort of consecutive patients admitted for stroke or transient ischemic attack (TIA) with symptomatic intracranial stenosis confirmed by digital subtraction angiography in a single-center retrospective study. Angiograms were graded systematically in a blinded fashion for antegrade and collateral flow, using Thrombolysis in Cerebral Infarction (TICI) and American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading, respectively, and integrated to a simple composite circulation score. Demographic and clinical variables, modified Rankin Scale (mRS) scores at 3 months, recurrent stroke or TIA in 12 months were collected. Uni- and multivariate analyses were performed to identify independent predictors of good outcome (mRS 0-2) and recurrence in a logistic regression model. Results: Among 69 patients with pure intracranial atherosclerosis ≥50%, compromised antegrade flow (TICI 0-2a) was observed in 26 (36%) patients and was associated with more severe arterial stenosis (mean 86 vs. 74%, p = 0.001). Poor collateral compensation resulting in a poor composite circulation score was observed in 8 (12%) patients. Patients with a good circulation score (n = 61, 88%) had preserved flow, which was associated with more favorable outcome (OR 7.50, 95% CI 1.11-50.7, p = 0.04) and less recurrent TIA or stroke (OR 0.18, 95% CI 0.04-0.96, p = 0.04). Prognosis was not significantly associated with antegrade or collateral grade per se. Conclusion: Good collateral compensations are more important in patients with symptomatic intracranial stenosis and compromised antegrade flow, and are associated with favorable outcome and less recurrence risk. The feasibility of composite flow assessment should be explored in future studies to identify high-risk intracranial stenosis with compromised hemodynamics. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: To date limited information regarding outcome-modifying factors in patients with acute intracranial large artery occlusion (ILAO) in the anterior circulation is available. Leukoaraiosis (LA) is a common finding among patients with ischemic stroke and has been associated with poor post-stroke outcomes but its association with ILAO remains poorly characterized. This study sought to clarify the contribution of baseline LA and other common risk factors to 90-day outcome (modified Rankin Scale, mRS) after stroke due to acute anterior circulation ILAO. Methods: We retrospectively analyzed 1,153 consecutive patients with imaging-confirmed ischemic stroke during a 4-year period (2007-2010) at a single academic institution. The final study cohort included 87 patients with acute ILAO subjected to multimodal CT imaging within 24 h of symptom onset. LA severity was assessed using the van Swieten scale on non-contrast CT. Leptomeningeal collaterals were graded using CT angiogram source images. Hemorrhagic transformation (HT) was determined on follow-up CT. Multivariate logistic regression controlling for HT, treatment modality, demographic, as well as baseline clinical and imaging characteristics was used to identify independent predictors of a poor outcome (90-day mRS >2). Results: The median National Institutes of Health Stroke Scale (NIHSS) at baseline was 15 (interquartile range 9-21). Twenty-four percent of the studied patients had severe LA. They were more likely to have hypertension (p = 0.028), coronary artery disease (p = 0.015), poor collaterals (p < 0.001), higher baseline NIHSS (p = 0.003), higher mRS at 90 days (p < 0.001), and were older (p = 0.002). Patients with severe LA had a uniformly poor outcome (p < 0.001) irrespective of treatment modality. Poor outcome was independently associated with higher baseline NIHSS (p < 0.001), worse LA (graded and dichotomized, p < 0.001), reduced leptomeningeal collaterals (graded and dichotomized, p < 0.001), presence of HT (p < 0.001), presence of parenchymal hemorrhages (p = 0.01), baseline mRS (p = 0.002), and older age (p = 0.043). The association between severe LA (p = 0.0056; OR 13.86; 95% CI 1.94-∞) and baseline NIHSS (p = 0.0001; OR 5.11; 95% CI 2.07-14.49 for each 10-point increase) with poor outcome maintained after adjustment for confounders in the final regression model. In this model, there was no significant association between presence of HT and poor outcome (p = 0.0572). Conclusion: Coexisting LA may predict poor functional outcome in patients with acute anterior circulation ILAO independent of other known important outcome predictors such as comorbid state, admission functional deficit, collateral status, hemorrhagic conversion, and treatment modality. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: Vessel size imaging is a novel technique to evaluate pathological changes of the microvessel density quantity Q and the mean vessel size index (VSI). As a follow-up study, we assessed these parameters for microscopic description of ischemic penumbra and their potentials in predicting lesion growth. Methods: Seventy-five patients with a perfusion-diffusion mismatch were examined within 24 h from symptom onset. We defined three regions of interest: the initial infarct (INF), the ischemic penumbra (IPE), and the healthy region (HEA) symmetric to the IPE. For 23 patients with a 6th-day follow-up, IPE regions were divided into areas of infarct growth and areas of oligemia. Result: The median values of Q and VSI were: for INF 0.29 s-1/3 and 15.8 μm, for IPE 0.33 s-1/3 and 20.6 μm and for HEA 0.36 s-1/3 and 17.4 μm. The Q in the IPE was significantly smaller than in HEA, and VSI was significantly larger. The Q with a threshold of 0.32 s-1/3 predicted the final infarction with a sensitivity of 69% and a specificity of 64%. Conclusions: The reduced Q and increased VSI in the IPE confirmed our previous pilot results. Although Q showed a trend to identify the severity of ischemia in an overall voxel population, its potential in predicting infarct growth needs to be further tested in a larger cohort including a clear status of reperfusion and recanalization. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Information is scare regarding the safety of intravenous thrombolysis in patients under anticoagulant treatment, given that this is an exclusion criterion in clinical trials. We analyzed the risk of hemorrhagic complications following thrombolysis in patients under treatment with low-molecular-weight heparins (LMWH) and oral anticoagulants (OA). Methods: In a multicentered prospective study of consecutive acute stroke patients treated with intravenous alteplase we recorded age, gender, baseline NIHSS score, treatment delay, risk factors, etiology and previous therapy. The neurological progress (National Institutes of Health Stroke Scale at 7 days) and functional evolution at 3 months (modified Rankin Scale score), mortality and symptomatic intracerebral hemorrhage (SICH) were compared between patients with LMWH or OA and those without prior anticoagulant therapy. Results: Of the 1,482 patients, 21 (1.4%) had received LMWH and 70 (4.7%) OA (international normalized ratio, INR, 0.9-2.0). Patients on OA were older, presented higher basal glucose levels, had been treated later and had a higher prevalence of hypertension, dyslipidemia, prior stroke, atrial fibrillation and cardioembolic pathologies. The severity of stroke on admission was similar in the different groups. The percentages of patients achieving independence (mRS 0-2) at 3 months were 33, 44 and 58 (LMWH, OA and no prior anticoagulant treatment, respectively; p = 0.02 for both comparisons of LMWH vs. no treatment and OA vs. no treatment); the mortality rates were 30, 25 and 12% (p = 0.010, p = 0.001, respectively) and the SICH were 14, 3 and 2% (p < 0.0001 for comparison of LMWH vs. no treatment). In the case of treatment with OA, the outcomes were independent of the INR value. Following adjustment for confounding variables, the prior use of OA was associated with higher mortality (OR: 2.15, 95% CI: 1.1-4.2; p = 0.026) but not with SICH transformation or lower probability of independence. The use of LMWH was associated with higher mortality (OR: 5.3, 95% CI: 1.8-15.5; p = 0.002), risk of SICH (OR: 8.4, 95% CI: 2.2-32.2; p = 0.002) and lower probability of achieving independence (OR: 0.3, 95% CI: 0.1-0.97; p = 0.043). Conclusions: The use of intravenous thrombolysis appears to be safe in patients previously treated with OA with INR levels <2 since there is no increase in SICH. The prior use of LMWH appears to increase the risk of SICH, death and dependence and, as such, the decision for systemic treatment with thrombolytic agents needs to be taken with caution in these cases. Larger case series are necessary to confirm these findings. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The effects of lipid levels on clinical outcomes after ischemic stroke are controversial. Whether admission lipid levels and prior statin use are associated with early intracerebral hemorrhage (ICH) and long-term functional outcome after recombinant tissue plasminogen activator (rt-PA) therapy for stroke patients was investigated. Methods: Ischemic stroke patients who received intravenous rt-PA from a multicenter registry were studied. Lipid levels on admission, including total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and triglyceride levels, as well as prior statin use, were assessed. The primary outcome was favorable outcome at 3 months corresponding to a modified Rankin Scale score ≤1. The secondary outcome was any or symptomatic ICH within the initial 36 h. Results: Of 489 enrolled patients (171 women, 70.8 ± 11.6 years old), 60 used statins prior to stroke, 93 developed ICH (19.0%), and 188 (38.4%) had a favorable 3-month outcome. Of the lipid levels, only the HDL-C level was an independent predictor of favorable outcome after multivariate adjustment for baseline characteristics (OR 1.95, 95% CI 1.10-3.47 per 1 mmol/l; p = 0.023) and after further adjustment for pretreatment radiological findings (OR 2.03, 95% CI 1.07-3.84; p = 0.029). For the 187 stroke patients without cardioembolism, the HDL-C level was more strongly associated with favorable outcome (OR 4.94, 95% CI 1.91-12.76 per 1 mmol/l; p = 0.001). There were no significant associations between ICH and any lipid levels. Prior statin use was not associated with outcomes. Conclusions: The admission HDL-C level was associated with favorable outcome 3 months after intravenous rt-PA therapy in stroke patients without cardioembolism. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The relevance of blood pressure variability (BPV) in the development of intracerebral hemorrhage (ICH) after intravenous thrombolysis (IVT) in acute stroke still remains uncertain. Methods: 427 consecutive patients treated with IVT in the years 2007-2009 were studied. Blood pressure (BP) values were analyzed from admission to follow-up imaging scan and described as mean, maximum, minimum, standard deviation (SD), difference between maximum and minimum, successive variation (SV) and maximum SV. ICH was categorized based on radiologic criteria and symptomatic ICH (sICH) was defined as ICH plus worsening of the National Institute of Health Stroke Scale by ≥4 points or leading to death. Three-month outcome was described by means of the modified Rankin Scale. Results: We observed any ICH in 51 (11.9%) and sICH in 10 (2.3%) patients. Systolic and diastolic BP profiles, including mean, maximum, minimum, SD, difference between maximum and minimum, SV and maximum SV, did not differ between ICH-negative, ICH-positive and sICH patients. In univariate analysis, high systolic BPV was associated with sICH (p = 0.03). A logistic regression model to predict ICH only found early CT findings (OR = 2.74, 95% CI = 1.47-5.11, p < 0.01) as independently associated with ICH. Poor 3-month outcome was independently predicted by age (OR = 0.96, 95% CI = 0.94-0.97, p < 0.001), NIHSS on admission (OR = 0.84, 95% CI = 0.80-0.87, p < 0.001), ICH (OR = 0.29, 95% CI = 0.13-0.66, p < 0.01) and high systolic BPV (OR = 1.68, 95% CI = 1.05-2.69, p < 0.05). Conclusions: We demonstrate that high BPV in patients receiving IVT leads to poor outcome but does not increase the risk of ICH/sICH. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Some studies suggest that low-frequency transcranial ultrasound (LFTUS) can enhance thrombolysis, but other studies suggest that it may have adverse effects on intracranial tissues. We previously reported that LFTUS with appropriate parameters was effective and safe in a normotensive rat model of thromboembolic middle cerebral artery occlusion (MCAO) stroke. The goal of this study was to test the safety of this strategy in a spontaneously hypertensive rat (SHR) model of permanent MCAO. Methods: Right MCAO was achieved in male SHRs using intraluminal nylon sutures. Rats exhibiting left hemiparesis were randomly assigned to one of four different groups: (1) normal saline (NS) group (n = 8), intravenous administration of NS as placebo at 3 h after MCAO; (2) NS+LFTUS group (n = 10), NS administration with simultaneous application of LFTUS (480.4 kHz, continuous wave, at an intensity of 0.3 W/cm2) for 1 h; (3) tissue plasminogen activator (tPA) group (n = 11), intravenous administration of alteplase (10 mg/kg body weight) over 1 h instead of NS; or (4) tPA+LFTUS group (n = 11), tPA administration and application of LFTUS. Twenty-four hours after treatment, neurological change was evaluated, and brains were removed and examined histologically. Results: There was no significant difference (p > 0.09) when comparing changes in neurologic status and body weight, infarct ratio, edema ratio, or hemorrhagic transformation among the four groups. Conclusions: Our findings suggest that sonothrombolytic treatment with LFTUS with appropriate parameters is safe when used for the treatment of ischemic stroke in hypertensive rats under the undesired permanent MCAO condition. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: 'Exception from informed consent for research' (EFIC) is a rigorous procedure regulated by the FDA that requires community assent but allows enrollment without patient or family consent. Recently, several acute stroke trials have explored the use of EFIC to improve enrollment. We obtained ischemic stroke survivors' opinions regarding hypothetical enrollment into a clinical trial at the time of their stroke without personal or proxy consent. Methods: During 2005, 460 ischemic stroke patients (or their proxy) who met case criteria were prospectively interviewed and followed. After 2 years, patients were asked to think back to the time of their stroke and indicate whether they would have wished to be enrolled in an acute stroke research study before individual or proxy consent could be obtained, understanding that consent would be sought as soon as possible thereafter, and they rated how agreeable they would have been to acute stroke research with different levels of invasiveness. Predictors of a positive opinion regarding the hypothetical research were analyzed using logistic regression. Variables included in the model were age, race, sex, education, initial NIHSS, modified Rankin Scale prior to stroke and 30 days after stroke, and proxy versus patient responder. Results: At 2 years after stroke, after excluding patient deaths, missing data or refusals, there were 194 patient/proxy responses included in this analysis. Overall, 72-79% of responses were favorable for chart review or blood draw without consent. The proportions answering agreeably to questions about medications or invasive strategies were smaller (62.9 and 59.8%). Older subjects were less likely to offer an agreeable response regarding use of medications [OR 0.97 per year (95% CI 0.94-0.99)] and invasive procedures [OR 0.97 per year (95% CI 0.94-0.99)]. Nonblacks tended to be more agreeable than blacks to invasive procedures. Men had twice the odds of being agreeable to blood draws than women. Conclusions: We found that the majority of interviewed ischemic stroke patients were agreeable to being enrolled in acute stroke research with exception from informed consent, although the rates of agreement were lower than we expected among a cohort of patients who had already agreed to research. Older subjects, black race, and women were less likely to agree to blood draws or treatment strategies. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to clarify the clinical impact of endovascular treatment (EVT) on acute cerebral large vessel occlusion using a nationwide survey of Japan conducted in 2009. Methods: Patients admitted within 24 h after stroke onset were registered retrospectively. Treatment selection, methods, and clinical results were analyzed. Results: A total of 1,963 patients (855 women, 1,108 men) treated in 2008 were registered from 68 medical centers in Japan. Mean age on admission was 74.1 ± 12.2 years (range 7-100 years). The first treatment was conservative therapy in 68%, intravenous tissue plasminogen activator (IV-tPA) in 21%, EVT in 9%, and combined IV-tPA + EVT in 2%. EVT mainly comprised angioplasty, intra-arterial thrombolysis and/or the combination of both. Patients treated ≤3 h after onset (1,286 cases) showed better clinical outcomes with combined IV-tPA + EVT than with conservative therapy, and significant differences in outcomes were seen for patients with occlusion of the basilar artery (p < 0.01) or middle cerebral artery (p < 0.01), but not the internal carotid artery. At >3 h after onset (677 patients), no IV-tPA was performed, and EVT was performed in 11%. Among the patients treated by EVT, there were significant differences in clinical outcome between complete recanalization (TIMI grade 3) and partial/no recanalization (TIMI grade 0-2) (p < 0.001; OR 5.98; 95% CI 3.27-10.96) and between any recanalization (TIMI grade 1-3) and no recanalization (TIMI grade 0) (p < 0.001; OR 36.15; 95% CI 4.88-267.53). Conclusions: This nationwide survey showed the efficacy of EVT with IV-tPA in patients with occlusion of the basilar or middle cerebral artery, but not of the internal carotid artery. The effects of new endovascular devices should be clarified in the near future. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: In patients with acute stroke, the hyperdense middle cerebral artery (MCA) and internal carotid artery (ICA) signs on CT scans are markers of early ischemia, but their prognostic implications remain unclear.The aims of this prospective study were to assess: (1) the occurrence rate of hyperdense MCA and/or ICA in patients admitted for acute ischemic stroke; (2) the risk factors for hyperdense MCA and/or ICA; (3) the correlation between hyperdense MCA and/or ICA and functional outcome at 3 months. Methods: Consecutive patients admitted with ischemic stroke between 1 January 2006 and 30 June 2010 were included in this prospective single-centre cohort study. Results: 1,010 patients (mean age 71.9 years; 56.7% males) were included in the study. Among these patients, 148 (14.7%; mean age 71.2 years; 52% males) had hyperdense MCA and/or ICA. Overall, 163 patients (16.1%) had a final infarct covering more than one third of the MCA territory. Seventy-eight of 148 patients (52.7%) with hyperdense MCA and/or ICA had an infarct involving more than one third of the MCA territory compared to 85 of the 862 patients without artery hyperdensity (9.9%). At 3 months, 18 patients were lost to follow-up, 325 patients (32.8%) were disabled and 165 died (16.5%). Age (OR 1.06 for 1 added year; 95% CI 1.04-1.08), National Institute of Health Stroke Scale score for 1 added point on admission (OR 1.2; 95% CI 1.2-1.3), stroke due to atherosclerosis (OR 2.3; 95% CI 1.0-5.4), hemorrhagic transformation of the ischemic lesion (OR 2.2; 95% CI 1.0-4.9), and hyperdense MCA and/or ICA (OR 2.0; 95% CI 1.0-4.0) were associated with adverse outcome. Conclusions: In this prospective cohort of patients with acute ischemic stroke, we observed an incidence of hyperdense MCA and/or ICA arteries of about 15%; hyperdense MCA and/or ICA were associated with a final infarct involving more than one third of the MCA territory and poor functional outcome at 3 months. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Internal carotid artery (ICA) occlusion, present in up to 15% of stroke patients, may cause low-flow transient ischemic attacks (TIAs) like limb shaking (LS) or retinal claudication (RC). Reliable data on the frequency of these phenomena and their potential prognostic relevance are still sparse. Aims: To provide more data about the frequency of low-flow TIA and investigate their influence on outcome. Material and Methods: Medical records of 260 consecutive patients with symptomatic ICA occlusion were carefully reviewed (survey period: January 2000 to December 2006). Baseline stroke severity and outcome at 90 days and in the long term were assessed. All patients were specifically questioned about symptoms of LS and RC, were exposed to bright light (pupillary testing) and carefully watched during testing of posture/gait and early mobilization. Results: LS, RC or both occurred in 28.6, 9.5 and 2.7%, respectively, of patients eligible for a thorough assessment of low-flow TIAs (n = 147). An adverse outcome was more likely in patients with LS than in those without at day 90 (modified Ranking Scale ≥4, 45.2 vs. 21.9%, p = 0.005) and in the long term (median, 37 months) (52.7 vs. 23.1%, p < 0.001). In a multivariable analysis, prognostic relevance was found to be independent of baseline stroke severity (National Institutes of Health Stroke Scale). There was also a tendency towards higher rates of recurrent stroke and TIA in limb shakers. RC had no prognostic relevance regarding functional outcome and recurrent events. Conclusion: In patients with ICA occlusion, RC and LS are more common than previously assumed. The presence of LS is associated with a worse outcome independent of initial stroke severity and patient characteristics. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Aspirin is a proven antiplatelet agent in acute ischemic stroke, and there are no current guidelines for other antiplatelet treatments. We aimed to compare the efficacy and safety of cilostazol with aspirin in acute stroke. Methods: Patients with measurable neurological deficits (NIHSS score ≤15) within 48 h of onset were randomly assigned to cilostazol (200 mg/day) or aspirin (300 mg/day) for 90 days. The primary endpoint was a modified Rankin Scale (mRS) score of 0-2 at 90 days. Cardiovascular events, bleeding complications, and other functional outcomes were also assessed. Statistical analysis was carried out by intention-to-treat and per-protocol bases. This trial is registered with ClinicalTrials.gov (NCT00272454). Results: In total, 458 patients were enrolled (mean age of 63 years, median NIHSS of 3), and mRS at 90 days was obtained in 447 patients. The primary endpoint was achieved in 76% (173/228) of those randomized to cilostazol and in 75% (165/219) assigned to aspirin, which supported the pre-specified non-inferiority of cilostazol to aspirin (95% CI of proportion difference: -6.15 to 7.22%, p = 0.0004). These results were also supported by per-protocol analysis (p = 0.045). Cardiovascular events occurred in 6 patients (3%) treated with cilostazol, and in 9 patients (4%) treated with aspirin (p = 0.41). Adverse events were more common in cilostazol-treated patients during the trial (91 vs. 85%, p = 0.055), while the frequencies of bleeding complications (cilostazol 11%, aspirin 13%, p = 0.43) or drug discontinuation (cilostazol 10%, aspirin 7%, p = 0.32) were not different. Conclusion: Cilostazol is feasible in acute ischemic stroke, and comparable to aspirin in its efficacy and safety. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Perfusion computed tomography (PCT) shows promise in acute stroke assessment. However, the accuracy of CT perfusion thresholds in defining the acute infarct core remains uncertain. Method: Concurrent PCT and MRI-DWI performed 3-6 h after symptoms onset were assessed in 57 ischemic stroke patients. PCT was compared to DWI images to define the infarct core using a pixel-based receiver operating characteristic curve analysis to calculate the area under the curve (AUC) for thresholds from PCT maps that were coregistered with the DWI slice location. Results: A relative cerebral blood flow (CBF) of 45% of the contralateral hemisphere was found to be the most accurate threshold for describing the infarct core (AUC 0.788), and it was also by far the most frequent threshold with the highest AUC across patients. Conclusion: CBF thresholds on PCT define the acute infarct core more accurately than do other PCT thresholds, including a cerebral blood volume of 2 ml/100 g. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The rate of early post-stroke epileptic seizures ranges from 2 to 33%. This wide range is likely due to differences in study design, patient selection and type of neurophysiological monitoring. Electroencephalography (EEG), which is not used in the routine work-up of acute stroke, is the best neurodiagnostic technique for detecting epileptic activity, especially in patients with non-convulsive post-stroke epileptic activity. The aim of this study was to analyze patterns on EEGs performed within 24 h of stroke onset, and to investigate correlations between these patterns and the occurrence of early epileptic seizures and status epilepticus (SE), vascular risk factors, stroke subtypes and short-term outcome. Methods: We prospectively studied 232 patients (mean age 71 ± 12 years; 177 ischemic strokes and 55 hemorrhagic). EEG recording was performed within 24 h from hospitalization. The follow-up lasted 1 week. Results: Fifteen patients (6.5%) had early seizures within 24 h; 10 of these patients had focal SE with or without secondary generalization. EEG revealed sporadic epileptiform focal abnormalities in 10% and periodic lateralized epileptiform discharges (PLEDs) in 6%. SE was recorded in 71.4% of patients with PLEDs. At the multivariate analysis, only early epileptic manifestations (p < 0.001) were independently associated with PLEDs. Conclusions: Our study confirms that seizures are not frequent in the early phase of acute stroke and occur prevalently as focal SE at onset. EEG may help to detect specific patterns, such as PLEDs, that are closely related to early seizures. EEG monitoring should be performed in order to detect purely electrographic seizures. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Calcium concentrations in serum are maintained within an exquisitely narrow range. Our aim was to examine the association between serum calcium and albumin-adjusted calcium (calciumadj) levels and stroke outcome in a cohort of unselected patients with acute stroke. Methods: Consecutive patients hospitalized due to acute stroke (ischemic or intracerebral hemorrhage) throughout a large medical center were systematically assessed and followed for 1 year. Baseline total calcium and calciumadj levels were collapsed into groups of low (<8.6 mg/dl), normal (8.7-9.9 mg/dl) and high (>10 mg/dl) levels and linear and quadratic relations with outcome were examined. Result: Among 784 patients (mean age 70.7 ± 12.5 years, 42.5% females), the mean ± SD total calcium level was 9.3 ± 0.6 mg/dl. For total calcium, the adjusted hazard ratio (HR) for all-cause death over 1 year was 1.83 [95% confidence interval (CI) 1.22-2.75] among patients with low versus normal levels. For calciumadj, the adjusted HR for all-cause death among women was over 3-fold higher among patients with high calciumadj levels versus those with normal levels (3.31; 95% CI 1.70-6.46), while no such associations were observed among men. In models developed to estimate the linear and quadratic relations, each unit increment in total calcium squared was associated with an increased adjusted HR of all-cause death over 1 year (p = 0.02) confirming nonlinear associations, and each unit increment in calciumadj squared was associated with an increased adjusted HR of all-cause death over 1 year among women (p < 0.001) but not among men (p = 0.70). Conclusions: Serum calcium concentrations are a marker of mortality in acute stroke patients, but the associations are not linear, increasing at both extremes of calcium levels. Our findings suggest that long-term survival is optimal in a distinct range of serum calcium levels. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Backgrounds: Our aim was to confirm the utility of paramedics using the Kurashiki Prehospital Stroke Scale (KPSS), with a maximum score of 13, for patients who may be eligible for administration of intravenous tissue plasminogen activator (IV t-PA). Methods: The subjects comprised acute stroke and transient ischemic attack (TIA) patients transferred to our hospital by paramedics. We analyzed correlations between KPSS and the National Institutes of Health Stroke Scale (NIHSS). Patients admitted within 3 h of onset were categorized into 2 groups: KPSS ≥4 and KPSS <4. We compared the proportion of patients receiving IV t-PA between the groups. Results: Among 430 consecutive patients (mean age = 73 years; 266 men), paramedics recorded KPSS for 256 patients (59.5%). Excellent correlation was observed between KPSS and NIHSS in all 256 patients (R = 0.766; p < 0.001) and in 94 patients (ischemic stroke and TIA with symptoms on admission) admitted within 3 h of onset (R = 0.706; p < 0.001). Among these 94 patients, IV t-PA was more frequently given in the KPSS ≥4 group (30 of 58 patients, 51.7%) than in the KPSS <4 group (5 of 36 patients, 13.9%; p < 0.001). Arterial occlusion was more frequently observed in the KPSS ≥4 group (57.9 vs. 31.4%, p = 0.018). KPSS ≥4 was independently associated with administration of IV t-PA (odds ratio = 4.7; 95% confidence interval = 1.5-14.6, p = 0.008). Conclusion: Reliable concordance between KPSS and NIHSS was found in acute stroke and TIA patients. KPSS ≥4 represents a good score to indicate prospective t-PA patients among those admitted within 3 h of stroke onset. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: In this study, we tried to identify predictors of acute poststroke seizures (aPSS) in stroke patients. Methods:We analyzed a large prospective hospital-based stroke registry in Germany. 58,874 patients with the diagnosis of transient ischemic attack (TIA), ischemic stroke (IS) or intracerebral hemorrhage (ICH) were admitted within 24 h after symptom onset. Predictors for aPSS were identified using multivariate regression analysis adjusted for age, gender, stroke severity, vascular risk factors, acute nonneurologic infection, history of TIA and length of hospital stay. Results: aPSS occurred in 0.7% of patients with TIA (mean duration of hospitalization 8 days), in 2.2% of patients with IS (12 days) and in 5.1% of patients with ICH (13 days). A lower age, a higher stroke severity, acute nonneurologic infection, a history of diabetes mellitus and a history of preceding TIA were identified to be independent predictors of aPSS in IS, whereas younger age, acute infection and a history of TIA were found predictive for aPSS in ICH. Conclusions: This study characterized so far unknown predictors of aPSS and may help to improve the identification of patients with a high risk of aPSS. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Transcranial Doppler (TCD) ultrasound can demonstrate dynamic information. We aimed to evaluate whether TCD generates useful additional information in the emergency room after a multimodal stroke imaging protocol and also whether this modified the management of patients with cerebral infarction. Methods: Patients admitted between April 2006 and June 2007 with ischemic stroke of less than 24 h were subjected to a protocol consisting of noncontrast brain CT, computed tomography angiography, diffusion-weighted magnetic resonance imaging and then TCD within the following 6 h by an observer blinded to the results of imaging studies. Results: Seventy-nine patients were included. The imaging protocol was performed 457 (±346) min after stroke symptoms and TCD after 572 (±376) min. TCD provided additional information in 28 cases (35.4%, 95% CI 25.7–46.4). More that one piece of additional information was obtained in 6 patients. The most frequent additional information was collateral pathways. Multivariate analysis demonstrated that intracranial vessel occlusion was the variable most associated with additional information. In 7 patients (8.8%, 95% CI 4.3–17.1), additional information changed management: in 4 an additional angiography was performed, in 2 patients angiography was suspended and in 1 aggressive neurocritical care was indicated. Patients with NIHSS >10 were significantly more likely to have their initial treatment changed (p = 0.004). Conclusions: TCD can provide additional information to a multimodal acute ischemic stroke imaging protocol in a third of patients. This can result in changes in the management in some of these patients. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The Canadian Neurological Scale (CNS) and the National Institutes of Health Stroke Scale (NIHSS) are among the most reliable stroke severity assessment scales. The CNS requires less extensive neurological evaluation and is quicker and simpler to administer. Objective: Our aim was to develop and validate a simple conversion model from the CNS to the NIHSS. Methods: A conversion model was developed using data from a consecutive series of acute-stroke patients who were scored using both scales. The model was then validated in an external dataset in which all patients were prospectively assessed for stroke severity using both scales by different observers which consisted of neurology residents or stroke fellows. Results: In all, 168 patients were included in the model development, with a median age of 73 years (20–94). Men constituted 51.8%. The median NIHSS score was 6 (0–31). The median CNS score was 8.5 (1.5–11.5). The relationship between CNS and NIHSS could be expressed as the formula: NIHSS = 23 – 2 × CNS. A cohort of 350 acute-stroke patients with similar characteristics was used for model validation. There was a highly significant positive correlation between the observed and predicted NIHSS score (r = 0.87, p < 0.001). The predicted NIHSS score was on average 0.61 higher than the observed NIHSS score (95% CI = 0.31–0.91). Conclusions: The CNS can be reliably converted to the NIHSS using a simple conversion formula: NIHSS = 23 – 2 × CNS. This finding may have a practical impact by permitting reliable comparisons with NIHSS-based evaluations and simplifying the routine assessment of acute-stroke patients in more diverse settings. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Previous clinical trials have shown that Neuroaid® (MLC601), a traditional Chinese medicine, shows good tolerability and superiority over another traditional Chinese medicine in terms of neurological disability and functional outcome and thus may be beneficial as part of a poststroke rehabilitation program. The safety of MLC601 on hemostasis, hematology and biochemistry has been established in normal subjects and patients with nonacute stroke over a short treatment period. We assessed the safety of Neuroaid in patients with acute stroke treated for 3 months in a substudy of an ongoing randomized placebo-controlled trial. Methods: Laboratory tests (biochemical, hematological and electrocardiogram) were conducted at the month 3 follow-up, in addition to baseline tests. A total of 114 patients were recruited. As there were 13 dropouts, a total of 52 patients on MLC601 and 49 on placebo were available for analysis. Serious adverse events (SAEs) were also analyzed. Results: There were no statistically or clinically significant differences between treatment groups in biochemical, hematological or electrocardiogram tests at month 3, nor any statistically or clinically significant differences in the absolute and relative changes of the various parameters between baseline and 3 months. SAEs were similar and were those commonly seen in stroke patients. Conclusions: Longer-term laboratory safety data show no differences between MLC601 and placebo, confirming the safety of MLC601 in acute stroke patients receiving a 3-month treatment. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: A malignant profile of early brain ischemia has been demonstrated in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) trial. Patients with a malignant profile had a low chance for an independent functional outcome despite thrombolysis within 3–6 h. We sought to determine whether CT angiography (CTA) could identify a malignant imaging profile within 3 h from symptom onset. Methods: We studied consecutive patients (04/02–09/07) with anterior circulation stroke who received CTA before intravenous thrombolysis within 3 h. We assessed the Alberta Stroke Program Early CT Score (ASPECTS) on CTA source images (CTASI). Intracranial thrombus burden on CTA was assessed with a novel 10-point clot burden score (CBS). We analyzed percentages independent (modified Rankin Scale score ≤2) and fatal outcome at 3 months and parenchymal hematoma rates across categorized combined CTASI-ASPECTS + CBS score groups where 20 is best and 0 is worst. Results: We identified 114 patients (median age 73 years [interquartile range 61–80], onset-to-tPA time 129 min [95–152]). Among 24 patients (21%) with extensive hypoattenuation on CTASI and extensive thrombus burden (combined score ≤10), only 4% (1/24) were functionally independent whereas mortality was 50% (12/24). In contrast, 57% (51/90) of patients with less affected scores (combined score 11–20) were functionally independent and mortality was 10% (9/90; p < 0.001). Parenchymal hematoma rates were 30% (7/23) vs. 8% (7/88), respectively (p = 0.008). Conclusion: CTA identifies a large hyperacute stroke population with high mortality and low likelihood for independent functional outcome despite early thrombolysis. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Objective: Infarct volume and patterns may vary according to the stroke subtype. Within each stroke subtype, however, it is not clear if the infarct volume and patterns are affected by the risk of cardioembolism (CE) and the degree of arterial stenosis. Patients and Methods: We included consecutive patients with acute symptomatic ischemic lesions on diffusion-weighted imaging (DWI) performed within 48 h of symptom onset who had CE or internal carotid artery disease (ICAD). CE was divided into high-risk and medium-risk groups, and ICAD was divided into ICA occlusion (ICAO) and ICA stenosis (ICAS ≥50%) groups. DWI lesion patterns were classified as single versus multiple, and as large territorial versus perforating artery (large ≥2 cm, small <2 cm) versus pial artery versus border zone infarct. Infarct volumes and National Institutes of Health Stroke Scale (NIHSS) scores were obtained. Results: Of the 167 patients included, 120 had CE (98 high-risk, 22 medium-risk) and 47 had ICAD (25 ICAO, 22 ICAS). The infarct volume was largest in the high-risk CE group, followed by the ICAO group. The infarct volumes in the medium-risk CE and ICAS groups were similar. Infarct volumes correlated with NIHSS scores. Single and large territorial infarcts were more common in the high-risk CE group, while multiple lesions as well as pial and border zone infarcts were more frequent in the ICAD subgroups. The lesion patterns of the medium-risk CE and ICAD groups were relatively similar. Conclusions: CE and ICAD have heterogeneous radiologic characteristics depending on the risk of embolism and the degree of carotid stenosis. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Atheromatous plaques of the aortic arch that extend to the origin of its branches may cause stroke. The frequency and clinical implications of plaque at the origin of the left subclavian artery (LSCA) in patients with recent ischemic stroke were investigated. Methods: We studied 347 consecutive patients (223 men, 69 ± 12 years) who developed symptomatic ischemic stroke and underwent transesophageal echocardiography (TEE). Results: The origin of the LSCA was identified in 303 of 347 patients (87.3%). Plaque ≥1.0 mm was detected in 108 of the 303 patients (35.6%), ranging between 1.0 and 6.1 mm (median, 2.5 mm). Patients having thicker plaque (≥2.5 mm) were older (p = 0.012) and more commonly took antiplatelets prior to stroke (p = 0.038) than patients with no plaque and those with thinner plaque (<2.5 mm). Of the aortic arch findings detected on TEE, maximum intima-media thickness (IMT) was the highest (p < 0.001) in patients with thicker plaque, and large plaque (≥4.0 mm) (p = 0.017), ulcerative plaques (p < 0.001), and spontaneous echo contrasts (p = 0.001) were identified most commonly in patients with thicker plaque. The frequency of infarcts involving the posterior circulation was similar among the three groups. After multivariate adjustment, maximum IMT of the aortic arch was independently related to thicker plaque at the LSCA origin (OR = 1.24, 95% CI = 1.03–1.51, p = 0.024, per 1-mm increase). Conclusions: Atheromatous plaque at the origin of the LSCA was present in approximately one third of patients with a recent ischemic stroke. High IMT at the aortic arch was independently related to the presence of thick plaque at the LSCA origin. The present study does not support the concept that plaque at the LSCA origin may be associated with posterior circulation infarction. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Intracranial arterial lesions are important causes of ischemic stroke, particularly in the Asian population. Of the intracranial lesions, the etiology of isolated anterior cerebral artery (ACA) territory infarction is not fully elucidated. The purpose of this study was to determine the etiological and clinical characteristics of patients with isolated ACA territory infarction, especially those with ACA dissection. Methods: Of 3,115 consecutive patients with acute ischemic stroke, 42 patients (1.3%, 30 men, 38–88 years old) having an isolated ACA territory infarction were studied. Infarcts were principally verified by diffusion-weighted MRI, and vascular lesions were identified by MRA, CTA, or digital subtraction angiography. Three-dimensional rotational angiography was performed if needed. Results: Eighteen patients (43%) were diagnosed as having ACA dissection. The stroke subtypes of the other 24 patients included cardioembolism for 6 patients and large-artery atherosclerosis for 8. Patients with dissection were younger (p < 0.001) and heavier (p = 0.026), less commonly had heart disease (p = 0.002) and previous stroke (p = 0.002), and had lower initial systolic blood pressure (p = 0.029) and lower levels of D-dimer (p = 0.041) than patients without dissection. Stroke onset more commonly followed physical exertion (p = 0.013) and headache (p = 0.041) in patients with dissection than in patients without dissection. At hospital discharge, the modified Rankin scale score was lower in patients with dissection than in patients without dissection (p = 0.005). Conclusions: Arterial dissection was the most common vascular lesion underlying an isolated ACA territory infarction in our Japanese cohort. Patients with ACA dissection had unique baseline characteristics and unique conditions at stroke onset. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Purpose: The modified Rankin Scale (mRS), designed as a measure of disability in the community, has increasingly been administered in the acute stroke setting but has been poorly studied within the hospital environment. We prospectively studied the interrater reliability of the mRS in acutely hospitalised stroke patients and examined the effect of prior experience with the scale and use of a decision tool on the interrater agreement of trained raters. Methods: Patients <4 days after stroke were recruited. Individuals from 3 trained rater groups (experienced, inexperienced and inexperienced with decision tool) independently scored each patient within 6 h of each other. Agreement was measured with the intraclass correlation (ICC) and the weighted kappa statistic (κw), with systematic bias evaluated using the bias index. Results: Twelve raters scored 56 patients with overall agreement of ICC = 0.675. Agreement of κw = 0.686 was found between experienced and inexperienced raters but a modest systematic bias was present. Experience in rating patients appeared to play some role in affecting agreement but the decision tool did not improve the performance of inexperienced raters. Conclusions: Trained raters were found to have good interrater agreement overall when the mRS was scored in acute stroke patients but obvious problems with the interpretation and relevancy of the scale in this setting raise concerns about validity. The use of the mRS to rate disability in the acute hospital environment should be questioned. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background:Early classification of ischemic stroke subtype is important for secondary stroke prevention and may guide further investigations. Methods: Levels of coagulation activation [fibrinopeptide A (FPA), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT)] and fibrinolysis activation [plasmin-α2-antiplasmin complex (PAP), D-dimers] markers were measured in 98 consecutive patients with a first-ever acute ischemic stroke admitted within 12 h after symptom onset. Results: Median age was 67 years and 44% were women. Median time from symptom onset to blood sampling was 4 h. Stroke subtype was classified as ‘cardioembolic’ (54%), ‘large-artery atherosclerosis’ (11%), ‘small-vessel disease’ (5%), ‘other determined’ (9%) or ‘undetermined etiology’ (20%). Patients with cardioembolic stroke suffered more often from coronary artery disease than patients with other stroke etiologies (40 vs. 22%, p = 0.019). There were no differences in age, sex, stroke severity, time to blood sampling, frequency of hypertension, diabetes mellitus or current smoking. D-dimers (medians) were higher in patients with cardioembolic strokes than in those with other etiologies (615 vs. 322 μg/l, p < 0.001). No differences in F1+2, FPA, TAT or PAP levels were found. After multivariate analysis, higher D-dimer levels remained independently associated with cardioembolic stroke (p = 0.022). When measured within 6 h, D-dimers below 300 μg/l excluded cardioembolic stroke with a sensitivity of 100% and a specificity of 52%. Conclusions: Low D-dimer levels in the first few hours make a cardioembolic stroke unlikely, and may be useful to guide further investigations. Other coagulation markers were not useful in differentiating between different stroke etiologies. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Purpose: Fiberoptic endoscopic evaluation of swallowing (FEES) is a suitable method for dysphagia assessment after acute stroke. Recently, we developed the fiberoptic endoscopic dysphagia severity scale (FEDSS) for acute stroke patients, grading dysphagia into 6 severity codes (1 to 6; 1 being best). The purpose of this study was to investigate the impact of the FEDSS as a predictor of outcomes at 3 months and intermediate complications during acute treatment. Methods: A total of 153 consecutive first-ever acute stroke patients were enrolled. Dysphagia was classified according to the FEDSS, assessed within 24 h after admission. Intermediate outcomes were pneumonia and endotracheal intubation. Functional outcome was measured by the modified Rankin Scale (mRS) at 3 months. Multivariate regression analysis was used to identify whether the FEDSS was an independent predictor of outcome and intercurrent complications. Analyses were adjusted for sex, age and National Institutes of Health Stroke Scale (NIH-SS) on admission. Results: The FEDSS was found to predict the mRS at 3 months as well as but independent from the NIH-SS. For each additional point on the FEDSS, the likelihood of dependency at 3 months (mRS ≥ 3) raised by ∼50%. Each increase of 1 point on the FEDSS conferred a more than 2-fold increased chance of developing pneumonia. The odds for the necessity of endotracheal intubation raised by a factor of nearly 2.5 with each additional point on the FEDSS. Conclusions: The FEDSS strongly and independently predicts outcome and intercurrent complications after acute stroke. Thus, a baseline FEES examination provides valuable prognostic information for the treatment of acute stroke patients. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Leukocyte-platelet aggregates appear to be a stable and sensitive marker of platelet activation as suggested by studies in coronary heart disease. We tested the hypothesis that leukocyte-platelet aggregates are increased after ischemic stroke and investigated the contribution of different leukocyte subtypes to such increase. Methods: We serially determined granulocyte-, lymphocyte- and monocyte-platelet aggregates, using flow cytometry at days 1, 2, 3, 5, 7, 10, and 90 in patients with ischemic stroke (n = 45) and in age- and sex-matched healthy control subjects (n = 30). Results: Granulocyte-platelet aggregates (granulocytes with ≥1 platelet/μl) were more common in patients than control subjects from day 1 through day 10 (p < 0.04, respectively), but not on day 90 after stroke. The percentage of granulocytes forming aggregates was increased on days 1–3 after stroke but not at other time points. Lymphocyte-platelet aggregates were not more common at any time point after stroke. Total numbers and percentages of monocytes forming platelet aggregates were significantly increased on day 2 (p = 0.003), but not at other time points after stroke. Conclusion: The 3 leukocyte subtypes showed different kinetics regarding aggregate formation with platelets after ischemic stroke. Increase of monocyte-platelet aggregates is short-lived and may reflect an acute reaction to cerebral ischemia, whereas granulocyte-platelet aggregate formation persists into the subacute phase, suggesting that they are a particularly sensitive parameter reflecting both prothrombotic and inflammatory processes after stroke. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Hyperglycemia has been claimed to be associated with hemorrhagic transformation (HT) in patients with acute ischemic stroke treated with thrombolysis. The aim of this study was to assess whether the admission blood glucose level is related to HT in a prospective study in consecutive patients with acute ischemic stroke. Methods: Consecutive patients admitted for ischemic stroke to 4 Italian hospitals were included in this prospective cohort study. Results: Among 1,125 consecutive patients included in the analysis, 98 (8.7%) had HT: 62 (5.5%) had hemorrhagic infarction (HI) and 36 (3.2%) parenchymal hematoma (PH). A blood glucose level >110 mg/dl was found in 42.4% of the patients, a level between 110 and 149 mg/dl in 25.2%, and a level >150 mg/dl in 17.2%. At 3 months, 7 patients were lost at follow-up, 326 patients (29.2%) were disabled (modified Rankin score ≥3) and 129 died (11.5%). PH was associated with an increased risk of death or disability (OR 15.29, 95% CI 2.35–99.35). However, this was not the case for HT overall and HI. At logistic regression analysis, PH was predicted by high levels of admission blood glucose (OR 1.01, 95% CI 1.00–1.01 for 1 added mg/dl). The rate of PH was 2.1% in patients with <110 mg/dl, 3.6% in patients with a level between 110 and 149 mg/dl and 6.4% in patients with a level >150 mg/dl. The curve estimation regression model showed a significant linear increase in the risk of PH related to an increase in blood glucose levels (R2 = 0.007, p = 0.007). Conclusions: Hyperglycemia during acute ischemic stroke predisposes to PH, which in turn determines a nonfavorable outcome at 3 months. This relationship seems to be linear. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: We examined if transcranial Doppler (TCD) flow findings at the site of intracranial occlusions predict outcomes of stroke patients receiving intravenous rt-PA treatment. Subjects and Methods: TCD detected residual flow with the Thrombolysis in Brain Ischemia (TIBI) grading system before intravenous rt-PA bolus in patients with acute arterial intracranial occlusion. Timing and completion of early recanalization were measured for occlusive TIBI flow grades using TCD monitoring. Poor responders were defined as modified Rankin scores (mRS) >2 at 3 months. Results: A total of 361 patients with proximal arterial occlusion received intravenous rt-PA at 137.4 ± 36 min (median NIHSS 16). Mean age 69 ± 13, women: 168 (46.5%). Seventeen of 96 (17.7%) patients with TIBI 0, 41/124 (33.1%) with TIBI 1, 29/76 (38.2%) with TIBI 2 and 31/65 (47.7%) with TIBI 3 had achieved complete recanalization (p < 0.001). Higher NIHSS, SBP, glucose and lower TIBI grades were independent negative predictors of complete recanalization in the final logistic model. Patients with TIBI 0 had less probability of complete recanalization than patients with residual flow (TIBI 1–3) (ORadj 0.4, CI 95% 0.22–0.8, p = 0.008). Median time to recanalization in patients with TIBI 0 was longer (155 min, interquartile range 104–190 min) than with TIBI ≥1 (120 min, range 60–170 min, p = 0.01, Mann-Whitney U test). In the stepwise multiple linear regression models adjusting for baseline characteristics, the only 2 factors that independently associated with time to recanalization were: time to rt-PA treatment and the absent flow (TIBI 0) on baseline TCD. Absent flow (TIBI 0) was associated with a longer time of recanalization of 35.2 min (95% CI 0.3–70.1 min, p = 0.048). Poor outcomes at 3 months were found in 61.3% of patients with no residual flow (TIBI 0), 56.9% with minimal (TIBI 1), 51.5% with blunted (TIBI 2), and 33.9% with dampened (TIBI 3) flows (p = 0.012). Patients with TIBI 0 have a higher likelihood of poor outcome (OR 3.1, 95% CI 1.5–6.4, p = 0.002). Patients who achieved complete recanalization have ORadj 5.2 for good outcome (95% CI 2.8–9.8, p < 0.001). Conclusions: The pretreatment residual flow at intracranial occlusion predicts the likelihood of complete recanalization, time of recanalization and long-term outcome. No detectable residual flow indicates the least chance to achieve recanalization and recovery with systemic thrombolysis and may support an early decision for combined endovascular rescue. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The rapid differentiation between intracerebral haemorrhage (ICH) and ischaemic stroke (IS) using biomarker testing would allow the prehospital, cause-specific management of stroke patients. Based on single measurements made during the acute phase of stroke, the value of serum glial fibrillary acidic protein (GFAP) was reported to be higher in ICH patients than in IS patients. The aim of the present study was to characterise the diagnostic window of serum GFAP for differentiating between ICH and IS. Methods: 63 stroke patients admitted within 6 h of symptom onset were prospectively included. ICH (n = 18) and IS (n = 45) were diagnosed using brain imaging. Blood sampling was scheduled for 1, 2, 3, 4, 6, 12, 24 and 48 h after stroke onset (if applicable), and serum GFAP was measured using an ELISA test. Results: For the first 24 h after stroke, median GFAP values in IS patients remained below the detection limit. Between 2 and 6 h of stroke onset, serum GFAP was significantly higher in ICH patients than in IS patients (p < 0.001 for all 4 time points). According to a receiver operating characteristic curve analysis, the overall diagnostic accuracy of GFAP in differentiating between ICH and IS was >0.80 within the 2- to 6-hour time window. Two hours after stroke onset, serum GFAP values were significantly correlated with ICH volume (r = 0.755, p = 0.007). Conclusions: The time window between 2 and 6 h after stroke onset is best for using GFAP to differentiate between ICH and IS. In the very early phase (i.e. <2 h), sensitivity for detecting ICH is low, thus hampering the application of GFAP as a near-patient test in the prehospital phase. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Implementing thrombolytic therapy in a stroke unit (SU) profoundly affects the resources available to all patients admitted for suspected acute stroke. We examined the benefits of an acute stroke service to non-stroke patients in terms of length of hospitalization, and estimated the economic impact in terms of derived costs. Methods: We performed a historical follow-up study of 792 non-stroke patients admitted to our SU for suspected stroke before, during and after implementing thrombolysis as part of our service. Data on demographic and clinical characteristics, including imaging data and final diagnoses, and length of stay (LOS) were collected prospectively. Multivariate logistic regression analysis was performed to identify variables associated with LOS. Results: Median LOS for non-stroke patients in the SU decreased from 43.8 h (interquartile range, 19–96) to 23.5 h (16–44) after implementing thrombolytic therapy. Total hospital LOS for non-stroke patients decreased from 52.7 (22–147) to 28.7 (21–124) h during the same period. Initial magnetic resonance imaging was associated with shorter LOS in the SU. The derived cost reductions from shorter LOS reduced the costs of implementing recombinant tissue plasminogen activator treatment. Conclusions: Stroke care reorganization following the introduction of thrombolytic treatment was associated with a 50% reduction in LOS for non-stroke patients admitted to the SU. Reduced LOS in the SU for non-stroke patients could further add to the cost-effectiveness of thrombolytic treatment. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The influence of antiplatelet agents (AP) in the development of a symptomatic intracranial haemorrhage (SICH) after intravenous rt-PA is not well known. We assessed the hypothesis that pre-treatment with AP may increase that risk. Methods: We studied data from consecutive patients with ischaemic stroke treated with intravenous rt-PA within the first 3 h after symptom onset. We recorded the antecedent of any AP therapy previous to thrombolysis. A follow-up CT was performed routinely 24–36 h after the infusion of rt-PA. Intracranial bleeding was categorized according to the criteria of the European Cooperative Acute Stroke Study II (ECASS II) into haemorrhagic infarction type 1 and 2 and parenchymal haemorrhage type 1 and 2. SICH was diagnosed if it was of the parenchymal haemorrhage type, occurred within the first 36 h and was associated with neurological deterioration. Results: Of a total of 605 patients, 137 (22.6%) were pre-treated with AP, most of them (n = 106) with aspirin. Any type of intracranial haemorrhage was observed in 119 patients (19.7%), without differences between the AP (18.4%) and the non-AP (20.2%) groups. Parenchymal haemorrhage was observed in 41 patients (8.5%) and SICH in 26 (4.3%). There was a non-significant rise in the frequency of SICH in the AP group compared with the non-AP group (6.6 vs. 3.6% p = 0.10). Conclusions: Pre-treatment with AP non-significantly increases the risk of SICH and therefore this antecedent should not be a contraindication for intravenous thrombolysis. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Thrombolysis remains the only proven therapy to benefit acute ischemic stroke (AIS) patients. Recent studies have introduced more sensitive outcome measures such as the shift analysis to detect a treatment effect in AIS trials and are also including imaging as a surrogate of injury. Methods: We conducted a cross-sectional, internet-based survey of academic neurologists regarding their attitudes, choices and understanding of various outcome measures in clinical trial design for AIS. The survey population consisted of neurologists who specialize in the care of stroke patients and are on faculty at university-affiliated hospitals in the USA. Results: 152 of 300 neurologists completed the survey. There were 79% men and 21% women. Among commonly used outcome scales in acute stroke, the most frequent ones selected for use as trial primary endpoints were the global statistic (59%), modified Rankin scale (mRS) (52%), and NIHSS (30%). When given choices about which outcome on the mRS would justify a therapeutic intervention, 54% chose a shift analysis of change in the distribution of outcomes and 39% chose a dichotomized outcome (mRS ≤2). A majority of respondents favored health transition states of 4–3, 3–2 and 2–1 on the mRS as clinically worthwhile. Only 2% of the respondents thought that a single transition point on the mRS was clinically meaningful. However, 20% of the respondents did not understand the shift analysis. In addition, nearly two thirds of the respondents believed that the presence of a mismatch on brain imaging is relevant to the success of neuroprotective agents. Conclusion: The majority of respondents accepted an analysis of the entire distribution of the mRS scores as an appropriate endpoint analytic technique in AIS trials and did not require the traditional dichotomized outcome to demonstrate a treatment effect; however, a better understanding of the shift strategy is needed. Our data also support the importance of incorporating mismatch imaging into future neuroprotection trials. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Standard selection criteria for thrombolysis typically exclude patients with acute ischemic stroke with unclear onset. Multimodal MRI screening may be able to identify those with a favorable benefit-risk ratio for thrombolysis. We aimed to evaluate the safety and efficacy of MRI-based thrombolysis in unclear-onset stroke (UnCLOS). Methods: We reviewed the thrombolysis database registries from 3 medical centers in Korea. Subjects received thrombolysis with intravenous tissue plasminogen activator (tPA) or combined intravenous tPA and intra-arterial urokinase within 3 h, or intra-arterial urokinase within 6 h from symptom detection. For patients with UnCLOS, MRI-specific eligibility criteria (i.e. positive perfusion-diffusion mismatch and absence of well-developed fluid-attenuated inversion recovery changes of acute diffusion lesions) were applied. Rates of immediate and 5-day recanalization, early neurological improvement and symptomatic intracranial hemorrhage (ICH) within 48 h after treatment and 3-month modified Rankin Scale (mRS) scores were compared between patients with UnCLOS and those with clear-onset stroke (CLOS). Results: 32 patients with UnCLOS and 223 patients with CLOS were included. Baseline characteristics were comparable between the two groups, except that the proportion of MRI screening was higher, and detection-to-door time and door-to-needle time were longer in the UnCLOS group (p < 0.01). Rates of recanalization (immediate, 81.3 vs. 63.1%; delayed, 80.6 vs. 69.1%), early neurological improvement (on day 1, 46.9 vs. 35.9%; on day 7, 50.0 vs. 49.3%), symptomatic ICH (6.3 vs. 5.8%) and 3-month outcome (mRS 0–1, 37.5 vs. 35.0%; mRS 0–2, 50.0 vs. 49.3%) did not differ between the UnCLOS and CLOS groups. Conclusion: These preliminary results suggest that thrombolysis based on MRI criteria may safely be applied to acute stroke patients with unclear onset. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: Platelets play a critical role in the pathogenesis of acute brain ischaemia. We studied the association between the degree of inhibition of platelet function by aspirin (ASA) and the severity and outcome of acute brain ischaemia. Methods: Platelet responsiveness to ASA was assessed in patients with acute brain ischaemia, treated with ASA since hospital admission. The degree of ASA responsiveness was assessed by optical aggregometry and categorized into patients with good response, partial response and complete unresponsiveness to ASA (good responders, partial responders and non-responders, respectively). An additional evaluation of responsiveness to ASA was performed by Impact-R (cone and platelet analyzer). Patients underwent serial clinical assessment during hospitalization, at discharge and during follow-up. Results: Among 105 patients (mean age 63 ± 12 years; 66% men), impaired ASA responsiveness at baseline as assessed by aggregometry was associated with increased stroke severity at baseline, unfavourable clinical course, and poor functional outcome during follow-up (p < 0.05 for all). Age-adjusted odds ratios in non-responders compared to good responders were 9.8 for severe stroke on admission (95% CI 2.8–34.9), 3.1 for lack of early clinical improvement (95% CI 1.1–8.8) and 8.6 for poor functional outcome during follow-up (95% CI 2.4–30.4). Less robust trends were observed with the Impact-R. Conclusions: Impaired responsiveness to ASA in acute brain ischaemia is common and is associated with worse neurological deficits at stroke onset, early clinical deterioration and poorer functional outcome. The clinical significance of these findings requires further evaluation in larger longitudinal studies. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]