Search

Delirium is a common complication in acute stroke patients, occurring in 15–35% of all stroke unit admissions and is associated with prolonged hospital stay and a poor post-stroke prognosis. Managing delirium in acute stroke patients necessitates an intensive and multiprofessional therapeutic approach, placing a significant burden on healthcare staff. However, dedicated practical recommendations for delirium management developed for the population of acute stroke patients are lacking. For this purpose, the Austrian Stroke Society, in cooperation with the Austrian Society of Neurology, the Austrian Society of Neurorehabilitation, and the Austrian Society of Psychiatry, Psychotherapy, and Psychosomatics has formulated an evidence-based position paper addressing the management of delirium in acute stroke patients. The paper outlines practical recommendations on the three pillars of care in stroke patients with delirium: (a) Key aspects of delirium prevention including stroke-specific delirium risk factors and delirium prediction scores are described. Moreover, a non-pharmacological delirium prevention bundle is presented. (b) The paper provides recommendations on timing and frequency of delirium screening to ensure early diagnosis of delirium in acute stroke patients. Moreover, it reports on the use of different delirium screening tools in stroke populations. (c) An overview of non-pharmacological and pharmacological treatment strategies in patients with delirium and acute stroke is presented and summarized as key recommendation statements. [ABSTRACT FROM AUTHOR]

Background: The PRE-hospital Stroke Treatment Organization was formed in 2016 as an international consortium of medical practitioners involved in pre-hospital treatment of patients with acute stroke. Aims: PRE-hospital Stroke Treatment Organization's mission is to improve stroke outcomes by supporting research and advocacy for pre-hospital stroke treatment in Mobile Stroke Units. PRE-hospital Stroke Treatment Organization will provide a platform to enhance collaborative research across the spectrum of acute stroke management in the prehospital setting. PRE-hospital Stroke Treatment Organization will also facilitate the appropriate proliferation and distribution of Mobile Stroke Units by providing a forum for professional communication, resource for public education, and stimulus for government, industry, and philanthropic support. Summary of review: In this "white paper", we describe the evidence supporting pre-hospital stroke treatment, progress to date, practical issues such as application in various environments and staffing, planned research initiatives, and organizational structure. Conclusions: PRE-hospital Stroke Treatment Organization is not-for-profit, with membership open to anyone involved (or hoping to become involved) in pre-hospital stroke care. PRE-hospital Stroke Treatment Organization has a Steering Committee comprised of members from Europe, U.S., Canada, Australia, and other regions having a Mobile Stroke Unit in operation. PRE-hospital Stroke Treatment Organization convenes satellite meetings for membership at the International Stroke Conference and European Stroke Congress each year to address the PRE-hospital Stroke Treatment Organization mission. The first research collaborations agreed upon are to: (1) develop a list of common data elements to be collected by all Mobile Stroke Unit programs and entered into a common research database, and (2) develop a protocol for investigating the natural history of hyper-acute Intracerebral Hemorrhage. [ABSTRACT FROM AUTHOR]

Introduction: Dysphagia can affect more than 50% of stroke patients in the acute phase. Aspiration pneumonia is a serious complication that can be prevented with dysphagia screening and assessment. Measurement of tongue elevation pressure is suggested to be a useful tool in aspiration risk screening. Objective: This study aimed to assess the diagnostic accuracy of maximum anterior tongue elevation strength (Pmax) in acute stroke care. Method: In this prospective study, data were collected in a neurology department (stroke center) where patients formed a consecutive case series. The sample consisted of thirty stroke patients who failed an initial dysphagia screening. Patients underwent anterior tongue elevation strength measurement (index test) during bedside dysphagia assessment by a speech-language pathologist and flexible endoscopic evaluation of swallowing (reference test) by an otorhinolaryngologist on the same day. Outcome variables (index values in kPa, reference values interpreted on the penetration-aspiration scale) were used for estimating measures of diagnostic accuracy in aspiration risk screening. Results: Ten patients aspirated on instrumental evaluation. At the cut-off point of ≤ 34 kPa the analysis showed 90% sensitivity, 35% specificity, 41% positive predictive value, and 88% negative predictive value. The area under the curve (AUC) for Pmax was AUC = 0.700 (95% CI [0.500–0.900]). Conclusion: Although individuals with low anterior tongue elevation strength tend to have a higher risk of aspiration, this variable alone is not capable of screening aspiration in acute stroke. In combination with a thorough noninstrumental bedside examination, it might have the potential to reduce the number of false positive cases. Further studies in this area would be worthwhile. [ABSTRACT FROM AUTHOR]

Acute stroke is one of the major causes of death and disabilities. Since the 1980s many clinical studies have been conducted to evaluate neuroprotective approaches to treat this important brain vascular event. However, to date the only drug approved (recombinant tissue plasminogen activator [rtPA]) represents a thrombolytic, nonneuroprotective approach. An important neuroprotective strategy is based on erythropoietin (EPO). Exogenously administered EPO exhibits neuroprotective effects in numerous animal models, through the activation of anti-apoptotic, anti-oxidant and anti-inflammatory pathways as well as through the stimulation of angiogenic and neurogenic events. The capability of EPO to cross the blood–brain barrier after systemic administration and its effective therapeutic window are advantages for human acute stroke therapy. However, a multicenter stroke trial where recombinant human EPO (rhEPO) was combined with rtPA had negative outcomes. The present paper reviews the EPO neuroprotective strategy and its mechanisms in ischemic stroke and in other human nervous system diseases. [ABSTRACT FROM PUBLISHER]

Several acute ischemic stroke mechanisms that cause lesion growth continue after treatment which is detrimental to long-term clinical outcome. The potential role of intravenous alteplase treatment (IVT), a standard in stroke care, in cessing the physiological processes causing post-treatment lesion development is understudied. We analyzed patients from the MR CLEAN-NO IV trial with good quality 24-hour and 1-week follow-up Non-Contrast CT scans. We delineated hypo- and hyper-dense regions on the scans as lesion. We performed univariable logistic and linear regression to estimate the influence of IVT on the presence (growth > 0 ml) and extent of late lesion growth. The association between late lesion growth and mRS was assessed using ordinal logistic regression. Interaction analysis was performed to evaluate the influence of IVT on this association. Of the 63/116 were randomized to included patients, IVT. Median growth was 8.4(−0.88–26) ml. IVT was not significantly associated with the presence (OR: 1.24 (0.57–2.74, p = 0.59) or extent (β = 5.1(−8.8–19), p = 0.47) of growth. Late lesion growth was associated with worse clinical outcome (aOR: 0.85(0.76–0.95), p < 0.01; per 10 ml). IVT did not influence this association (p = 0.18). We did not find evidence that IVT influences late lesion growth or the relationship between growth and worse clinical outcome. Therapies to reduce lesion development are necessary. [ABSTRACT FROM AUTHOR]

Following acute ischemic stroke, isolated subcortical lesions induce gray matter atrophy in anatomically connected, yet distant cortical brain regions. We expand on previous studies by analyzing cortical thinning in contralesional, homologous regions indirectly linked to primary stroke lesions via ipsilesional cortical areas. For this purpose, stroke patients were serially studied by magnetic resonance imaging (diffusion tensor imaging and high-resolution anatomical imaging) in the acute (days 3–5) and late chronic stage one year after stroke. We analyzed changes of gray and white matter integrity in 18 stroke patients (median age 68 years) with subcortical stroke. We applied probabilistic fiber tractography to identify brain regions connected to stroke lesions and contralesional homologous areas. Cortical thickness was quantified by semi-automatic measurements, and fractional anisotropy was analyzed. One year after stroke, significant decrease of cortical thickness was detected in areas connected to ischemic lesions (mean −0.15 mm; 95% CI −0.23 to −0.07 mm) as well as homologous contralateral brain regions (mean −0.13 mm; 95% CI −0.07 to −0.19 mm). We detected reduced white matter integrity of inter- and intrahemispheric fiber tracts. There were no significant associations with clinical recovery. Our results indicate that impact of subcortical lesions extends to homologous brain areas via transcallosal diaschisis. [ABSTRACT FROM AUTHOR]

Stroke is the fifth leading cause of death in the United States and a major cause of severe disability worldwide. Yet, recognizing the signs of stroke in an acute setting is still challenging and leads to loss of opportunity to intervene, given the narrow therapeutic window. A decision support system using artificial intelligence (AI) and clinical data from electronic health records combined with patients’ presenting symptoms can be designed to support emergency department providers in stroke diagnosis and subsequently reduce the treatment delay. In this article, we present a practical framework to develop a decision support system using AI by reflecting on the various stages, which could eventually improve patient care and outcome. We also discuss the technical, operational, and ethical challenges of the process. [ABSTRACT FROM AUTHOR]

Relative delays in blood-oxygen-level-dependent (BOLD) signal oscillations can be used to assess cerebral perfusion without using contrast agents. However, little is currently known about the utility of this method in detecting clinically relevant perfusion changes over time. We investigated the relationship between longitudinal BOLD delay changes, vessel recanalization, and reperfusion in 15 acute stroke patients with vessel occlusion examined within 24 h of symptom onset (D0) and one day later (D1). We created BOLD delay maps using time shift analysis of resting-state functional MRI data and quantified perfusion lesion volume changes (using the D1/D0 volume ratio) and severity changes (using a linear mixed model) over time. Between baseline and follow-up, BOLD delay lesions shrank (median D1/D0 ratio = 0.2, IQR = 0.03–0.7) and BOLD delay severity decreased (b = −4.4 s) in patients with recanalization, whereas they grew (median D1/D0 ratio = 1.47, IQR = 1.1–1.7) and became more severe (b = 4.3 s) in patients with persistent vessel occlusion. Clinically relevant changes in cerebral perfusion in early stroke can be detected using BOLD delay, making this non-invasive method a promising option for detecting tissue at risk of infarction and monitoring stroke patients following recanalization therapy. [ABSTRACT FROM AUTHOR]

Rationale: Bridging therapy with endovascular therapy (EVT) and intravenous thrombolysis (IVT) has been reported to improve outcomes for acute stroke patients with large-vessel occlusion in the anterior circulation. While the IVT may increase the reperfusion rate, the risk of hemorrhagic complications increases. Whether EVT without IVT (direct EVT) is equally effective as bridging therapy in acute stroke remains unclear. Aim: This randomized study of endovascular therapy with versus without intravenous tissue plasminogen activator for acute stroke with ICA and M1 occlusion aims to clarify the efficacy and safety of direct EVT compared with bridging therapy. Methods and design: This is an investigator-initiated, multicenter, prospective, randomized, open-treatment, blinded-endpoint clinical trial. The target patient number is 200, comprising 100 patients receiving direct EVT and 100 receiving bridging therapy. Study outcome: The primary efficacy endpoint is a modified Rankin Scale score of 0–2 at 90 days. Safety outcome measures are any intracranial hemorrhage at 24 h. Discussion: This trial may help determine whether direct EVT should be recommended as a routine clinical strategy for ischemic stroke patients within 4.5 h from onset. Direct EVT would then become the choice of therapy in stroke centers with endovascular facilities. Trial registration: UMIN000021488. [ABSTRACT FROM AUTHOR]

Nitrones (e.g. α-phenyl-N-tert-butyl nitrone; PBN) are cerebroprotective in experimental stroke. Free radical trapping is their proposed mechanism. As PBN has low radical trapping potency, we tested Sgk1 induction as another possible mechanism. PBN was injected (100 mg/kg, i.p.) into adult male rats and mice. Sgk1 was quantified in cerebral tissue by microarray, quantitative RT-PCR and western analyses. Sgk1+/+ and Sgk1-/- mice were randomized to receive PBN or saline immediately following transient (60 min) occlusion of the middle cerebral artery. Neurological deficit was measured at 24 h and 48 h and infarct volume at 48 h post-occlusion. Following systemic PBN administration, rapid induction of Sgk1 was detected by microarray (at 4 h) and confirmed by RT-PCR and phosphorylation of the Sgk1-specific substrate NDRG1 (at 6 h). PBN-treated Sgk1+/+ mice had lower neurological deficit (p<0.01) and infarct volume (p<0.01) than saline-treated Sgk1+/+ mice. PBN-treated Sgk1-/- mice did not differ from saline-treated Sgk1-/- mice. Saline-treated Sgk1-/- and Sgk1+/+ mice did not differ. Brain Sgk3:Sgk1 mRNA ratio was 1.0:10.6 in Sgk1+/+ mice. Sgk3 was not augmented in Sgk1-/- mice. We conclude that acute systemic treatment with PBN induces Sgk1 in brain tissue. Sgk1 may play a part in PBN-dependent actions in acute brain ischemia. [ABSTRACT FROM AUTHOR]

Background High blood pressure is common in acute stroke and associated with a worse functional outcome. Glyceryl trinitrate, a nitric oxide donor, lowers blood pressure in acute stroke and may improve outcome. Aims Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) tested the feasibility of performing a UK multicenter ambulance-based stroke trial, and the safety and efficacy of glyceryl trinitrate when administered by paramedics before hospital admission. Methods Paramedic-led ambulance-based multicenter prospective randomized single-blind blinded-endpoint parallel-group controlled trial of transdermal glyceryl trinitrate (given for four days) versus sham in patients with ultra-acute (<4 h) presumed stroke. Data are number (%), median (interquartile range) or mean (standard deviation). Results Recruitment ran from October 2015 to 31 May 2018. A total 1149 patients were recruited from eight UK ambulance services and taken to 54 acute hospitals. Baseline characteristics include: mean age 73 (15) years; female 555 (48%); median time from stroke to randomization 70 (45, 115) min; face-arm-speech scale score 2.6 (0.5); and blood pressure 162 (25)/92 (18) mmHg. The final diagnosis was ischemic stroke 52%, hemorrhagic stroke 13%, Transient Ischemic Attack (TIA) 9%, and mimic 25%. The main trial results will be presented in quarter 4 2018. The results will also be included in updated Cochrane systematic reviews, and individual patient data meta-analyses of all relevant randomized controlled trials. Conclusion It was feasible to perform a multicenter ambulance-based ultra-acute stroke trial in the UK and to treat with glyceryl trinitrate versus sham. The relatively unselected cohort of stroke patients is broadly representative of those admitted to hospital in the UK. Trial registration ISRCTN26986053. [ABSTRACT FROM AUTHOR]

Rationale Despite several large clinical trials assessing blood pressure lowering in acute stroke, equipoise remains particularly for ischemic stroke. The “Blood pressure in Acute Stroke Collaboration” commenced in the mid-1990s focussing on systematic reviews and meta-analysis of blood pressure lowering in acute stroke. From the start, Blood pressure in Acute Stroke Collaboration planned to assess safety and efficacy of blood pressure lowering in acute stroke using individual patient data. Aims To determine the optimal management of blood pressure in patients with acute stroke, including both intracerebral hemorrhage and ischemic stroke. Secondary aims are to assess which clinical and therapeutic factors may alter the optimal management of high blood pressure in patients with acute stroke and to assess the effect of vasoactive treatments on hemodynamic variables. Methods and design Individual patient data from randomized controlled trials of blood pressure management in participants with ischemic stroke and/or intracerebral hemorrhage enrolled during the ultra-acute (pre-hospital), hyper-acute (<6 h), acute (<48 h), and sub-acute (<168 h) phases of stroke. Study outcomes The primary effect variable will be functional outcome defined by the ordinal distribution of the modified Rankin Scale; analyses will also be carried out in pre-specified subgroups to assess the modifying effects of stroke-related and pre-stroke patient characteristics. Key secondary variables will include clinical, hemodynamic and neuroradiological variables; safety variables will comprise death and serious adverse events. Discussion Study questions will be addressed in stages, according to the protocol, before integrating these into a final overreaching analysis. We invite eligible trials to join the collaboration. [ABSTRACT FROM AUTHOR]

Background Communication between professionals, patients and families about palliative and end-of-life care after stroke is complex and there is a need for educational resources in this area. Methods To explore the key learning needs of healthcare professionals, a multidisciplinary, expert group developed a short electronic survey with open and closed questions, and then distributed it to six UK multiprofessional networks and two groups of local clinicians. Results A total of 599 healthcare professionals responded. Educational topics that were either definitely or probably needed were: ensuring consistent messages to families and patients (88%); resolving confiicts among family members (83%); handling unrealistic expectations (88%); involving families in discussions without them feeling responsible for decisions (82%); discussion of prognostic uncertainties (79%); likely mode of death (72%); and oral feeding for 'comfort' in patients at risk of aspiration (71%). The free-text responses (n = 489) and 82 'memorable' cases identified similar themes. Conclusion Key topics of unmet need for education in end-of-life care in stroke have been identified and these have infiuenced the content of an open access, web-based educational resource. [ABSTRACT FROM AUTHOR]

To assess hyperacute focal cerebral ischemia in rats on 3.0-Tesla diffusion-weighted imaging (DWI), we developed a novel voxel-wise lesion segmentation technique that overcomes intra- and inter-subject variation in apparent diffusion coefficient (ADC) distribution. Our novel technique involves the following: (1) intensity normalization including determination of the optimal type of region of interest (ROI) and its intra- and inter-subject validation, (2) verification of focal cerebral ischemic lesions at 1 h with gross and high-magnification light microscopy of hematoxylin-eosin (H&E) pathology, (3) voxel-wise segmentation on ADC with various thresholds, and (4) calculation of dice indices (DIs) to compare focal cerebral ischemic lesions at 1 h defined by ADC and matching H&E pathology. The best coefficient of variation was the mode of the left hemisphere after normalization using whole left hemispheric ROI, which showed lower intra- (2.54 ± 0.72%) and inter-subject (2.67 ± 0.70%) values than the original. Focal ischemic lesion at 1 h after middle cerebral artery occlusion (MCAO) was confirmed on both gross and microscopic H&E pathology. The 83 relative threshold of normalized ADC showed the highest mean DI (DI = 0.820 ± 0.075). We could evaluate hyperacute ischemic lesions at 1 h more reliably on 3-Tesla DWI in rat brains. [ABSTRACT FROM AUTHOR]

Overactivation of purinergic receptors during cerebral ischemia results in a massive release of neurotransmitters, including adenosine triphosphate (ATP), to the extracellular space which leads to cell death. Some hypothetical pathways of ATP release are large ion channels, such as calcium homeostasis modulator 1 (CALHM1), a membrane ion channel that can permeate ATP. Since this transmitter contributes to postischemic brain damage, we hypothesized that CALHM1 activation may be a relevant target to attenuate stroke injury. Here, we analyzed the contribution of CALHM1 to postanoxic depolarization after ischemia in cultured neurons and in cortical slices. We observed that the onset of postanoxic currents in neurons in those preparations was delayed after its blockade with ruthenium red or silencing of Calhm1 gene by short hairpin RNA, as well as in slices from CALHM1 knockout mice. Subsequently, we used transient middle cerebral artery occlusion and found that ruthenium red, a blocker of CALHM1, or the lack of CALHM1, substantially attenuated the motor symptoms and reduced significantly the infarct volume. These results show that CALHM1 channels mediate postanoxic depolarization in neurons and brain damage after ischemia. Therefore, targeting CALHM1 may have a high therapeutic potential for treating brain damage after ischemia. [ABSTRACT FROM AUTHOR]

The decision to perform decompressive hemicraniectomy (DHC) by default in malignant hemispheric stroke (MHS) remains controversial. Even under ideal conditions, DHC usually results in moderate to severe disability. The present study for the first time uses neuroimaging to identify independent outcome predictors in a prospective cohort of 96 MHS patients undergoing DHC. The primary outcome was functional status according to the modified Rankin Scale (mRS) at 12 months and categorized as favorable (mRS 0–3) or unfavorable (mRS 4–6). At 12 months, 19 patients (20%) reached favorable and 77 patients (80%) unfavorable outcome. The overall mean infarct volume was 328 ± 114 ml. Multivariable logistic regression identified age per year (OR 1.14, 95% CI 1.04–1.24; p = 0.005), infarct volume per cm3 (OR 1.012, 95% CI 1.003–1.022; p = 0.013), thalamic involvement (OR 8.65, 95% CI 1.04–72.15; p = 0.046) and postoperative pneumonia (OR 5.52, 95% CI 1.03–29.57; p = 0.046) as independent outcome predictors, which was confirmed by multivariable ordinal regression for age (p = 0.004) and infarct volume (p = 0.015). The infarct volume threshold for reasonable prediction of unfavorable outcome in our patients was 270 cm3, which in the future may help prognostication and development of clinical trials on DHC and outcome in MHS. [ABSTRACT FROM AUTHOR]

Stroke-associated pneumonia is a frequent complication after stroke associated with poor outcome. Dysphagia is a known risk factor for stroke-associated pneumonia but accumulating evidence suggests that stroke induces an immunodepressive state increasing susceptibility for stroke-associated pneumonia. We aimed to confirm that stroke-induced immunodepression syndrome is associated with stroke-associated pneumonia independently from dysphagia by investigating the predictive properties of monocytic HLA-DR expression as a marker of immunodepression as well as biomarkers for inflammation (interleukin-6) and infection (lipopolysaccharide-binding protein). This was a prospective, multicenter study with 11 study sites in Germany and Spain, including 486 patients with acute ischemic stroke. Daily screening for stroke-associated pneumonia, dysphagia and biomarkers was performed. Frequency of stroke-associated pneumonia was 5.2%. Dysphagia and decreased monocytic HLA-DR were independent predictors for stroke-associated pneumonia in multivariable regression analysis. Proportion of pneumonia ranged between 0.9% in the higher monocytic HLA-DR quartile (≥21,876 mAb/cell) and 8.5% in the lower quartile (≤12,369 mAb/cell). In the presence of dysphagia, proportion of pneumonia increased to 5.9% and 18.8%, respectively. Patients without dysphagia and normal monocytic HLA-DR expression had no stroke-associated pneumonia risk. We demonstrate that dysphagia and stroke-induced immunodepression syndrome are independent risk factors for stroke-associated pneumonia. Screening for immunodepression and dysphagia might be useful for identifying patients at high risk for stroke-associated pneumonia. [ABSTRACT FROM AUTHOR]

Crossed cerebellar diaschisis (CCD) is the phenomenon of hypoperfusion and hypometabolism of the contralateral cerebellar hemisphere caused by dysfunction of the related supratentorial region. Our aim was to analyze its influence on morphologic and functional outcome in acute ischemic stroke. Subjects with stroke caused by a large vessel occlusion of the anterior circulation were selected from an initial cohort of 1644 consecutive patients who underwent multiparametric CT including whole-brain CT perfusion. Two experienced readers evaluated the posterior fossa in terms of CCD absence (CCD-) or presence (CCDþ). A total of 156 patients formed the study cohort with 102 patients (65.4%) categorized as CCD- and 54 (34.6%) as CCDþ. In linear and logistic regression analyses, no significant association between CCD and final infarction volume (β=-0.440, p=0.972), discharge mRS≤2 (OR=1.897, p=0.320), or 90-day mRS≤2 (OR=0.531, p=0.492) was detected. CCDþ patients had larger supratentorial cerebral blood flow deficits (median: 164 ml vs. 115 ml; p=0.001) compared to CCD-patients. Regarding complications, CCD was associated with a higher rate of parenchymal hematomas (OR=4.793, p=0.035). In conclusion, CCD is frequently encountered in acute ischemic stroke caused by large vessel occlusion of the anterior circulation. CCD was associated with the occurrence of parenchymal hematoma in the ipsilateral cerebral infarction but did not prove to significantly influence patient outcome. [ABSTRACT FROM AUTHOR]

Several clinical trials have recently proven the efficacy of mechanical thrombectomy for treating ischemic stroke, within a six-hour window for therapy. To move beyond treatment windows and toward personalized risk assessment, it is essential to accurately identify the extent of tissue-at-risk (“penumbra”). We introduce a fully automated method to estimate the penumbra volume using multimodal MRI (diffusion-weighted imaging, a T2w- and T1w contrast-enhanced sequence, and dynamic susceptibility contrast perfusion MRI). The method estimates tissue-at-risk by predicting tissue damage in the case of both persistent occlusion and of complete recanalization. When applied to 19 test cases with a thrombolysis in cerebral infarction grading of 1–2a, mean overestimation of final lesion volume was 30 ml, compared with 121 ml for manually corrected thresholding. Predicted tissue-at-risk volume was positively correlated with final lesion volume (p < 0.05). We conclude that prediction of tissue damage in the event of either persistent occlusion or immediate and complete recanalization, from spatial features derived from MRI, provides a substantial improvement beyond predefined thresholds. It may serve as an alternative method for identifying tissue-at-risk that may aid in treatment selection in ischemic stroke. [ABSTRACT FROM AUTHOR]

To derive the reperfusion index best predicting clinical outcome of ischemic stroke patients, we retrospectively analysed the acute and 24-h computed tomography perfusion data of 116 patients, collected from two centres equipped with whole-brain computed tomography perfusion. Reperfusion index was defined by the percentage of the ischemic region reperfused from acute to 24-h computed tomography perfusion. Recanalization was graded by arterial occlusive lesion system. Receiver operator characteristic analysis was performed to assess the prognostic value of reperfusion and recanalization in predicting good clinical outcome, defined as modified Rankin Score of 0-2 at 90 days. Among previous reported reperfusion measurements, reperfusion of the Tmax>6s region resulted in higher prognostic value than recanalization at predicting good clinical outcome (area under the curve = 0.88 and 0.74, respectively, p = 0.002). Successful reperfusion of the Tmax>6 s region (≥60%) had 89% sensitivity and 78% specificity in predicting good clinical outcome. A reperfusion index defined by Tmax>2s or by mean transit time>l45% had much lower area under the curve in comparison to Tmax>6 s measurement (p < 0.001 and p = 0.003, respectively), and had no significant difference to recanalization at predicting clinical outcome (p = 0.58 and 0.63, respectively). In conclusion, reperfusion index calculated by Tmax>6s is a stronger predictor of clinical outcome than recanalization or other reperfusion measures. [ABSTRACT FROM AUTHOR]

Haemodynamic responses to spreading depolarizations (SDs) have an important role during the development of secondary brain damage. Characterization of the haemodynamic responses in larger brains, however, is difficult due to movement artefacts. Intrinsic optical signal (IOS) imaging, laser speckle flowmetry (LSF) and electrocorticography were performed in different configurations in three groups of in total 18 swine. SDs were elicited by topical application of KCl or occurred spontaneously after middle cerebral artery occlusion. Movement artefacts in IOS were compensated by an elastic registration algorithm during post-processing. Using movement-compensated IOS, we were able to differentiate between four components of optical changes, corresponding closely with haemodynamic variations measured by LSF. Compared with ECoG and LSF, our setup provides higher spatial and temporal resolution, as well as a better signalto-noise ratio. Using IOS alone, we could identify the different zones of infarction in a large gyrencephalic middle cerebral artery occlusion pig model. We strongly suggest movement-compensated IOS for the investigation of the role of haemodynamic responses to SDs during the development of secondary brain damage and in particular to examine the effect of potential therapeutic interventions in gyrencephalic brains. [ABSTRACT FROM AUTHOR]

We have characterized both acute and long-term vascular and metabolic effects of unilateral common carotid artery occlusion in mice by in vivo magnetic resonance imaging and positron emission tomography. This common carotid artery occlusion model induces chronic cerebral hypoperfusion and is therefore relevant to both preclinical stroke studies, where it serves as a control condition for a commonly used mouse model of ischemic stroke, and neurodegeneration, as chronic hypoperfusion is causative to cognitive decline. By using perfusion magnetic resonance imaging, we demonstrate that under isoflurane anesthesia, cerebral perfusion levels recover gradually over one month. This recovery is paralleled by an increase in lumen diameter and altered tortuosity of the contralateral internal carotid artery at one year post-ligation as derived from magnetic resonance angiography data. Under urethane/a-chloralose anesthesia, no acute perfusion differences are observed, but the vascular response capacity to hypercapnia is found to be compromised. These hemispheric perfusion alterations are confirmed by water [15O]-H2O positron emission tomography. Glucose metabolism ([18F]-FDG positron emission tomography) or white matter organization (diffusion-weighted magnetic resonance imaging) did not show any significant alterations. In conclusion, permanent unilateral common carotid artery occlusion results in acute and long-term vascular remodeling, which may have immediate consequences for animal models of stroke but also vascular dementia. [ABSTRACT FROM AUTHOR]

Stroke disrupts the brain's vascular supply, not only within but also outside areas of infarction. We investigated temporal delays (lag) in resting state functional magnetic resonance imaging signals in 130 stroke patients scanned two weeks, three months and 12 months post stroke onset. Thirty controls were scanned twice at an interval of three months. Hemodynamic lag was determined using cross-correlation with the global gray matter signal. Behavioral performance in multiple domains was assessed in all patients. Regional cerebral blood flow and carotid patency were assessed in subsets of the cohort using arterial spin labeling and carotid Doppler ultrasonography. Significant hemodynamic lag was observed in 30% of stroke patients sub-acutely. Approximately 10% of patients showed lag at one-year post-stroke. Hemodynamic lag corresponded to gross aberrancy in functional connectivity measures, performance deficits in multiple domains and local and global perfusion deficits. Correcting for lag partially normalized abnormalities in measured functional connectivity. Yet post-stroke FC-behavior relationships in the motor and attention systems persisted even after hemodynamic delays were corrected. Resting state fMRI can reliably identify areas of hemodynamic delay following stroke. Our data reveal that hemodynamic delay is common sub-acutely, alters functional connectivity, and may be of clinical importance. [ABSTRACT FROM AUTHOR]

Acute carotid stent thrombosis (ACST) is a rare complication that can lead to dramatic and catastrophic consequences. A rapid diagnosis and prompt recanalization of the internal carotid artery are needed to minimize the ischemic insult and the reperfusion injury. We reviewed the current literature on this devastating complication of CAS with the intention of investigating the potential causative factors and to define the appropriate management. According to our study discontinuation of antiplatelet therapy, resistance to antiplatelet agents and inherent or acquired thrombotic disorders are the main causes of thrombosis. Technical intraprocedural parameters such as dissection, atheroma prolapse, kinking of the distal part of internal carotid artery and embolic protection device occlusion can also result in early carotid stent thrombosis. Rapid reperfusion ensures an improved neurological outcome and a better prognosis in the short and long term. Thrombolysis, mechanical thrombectomy or thromboaspiration in combination with drug or thrombolytic therapy, surgical therapy and re-angioplasty are treatment options that have been used with encouraging results. In conclusion, optimal perioperative antiplatelet treatment as well as technical considerations regarding the carotid artery stenting plays a determinant role. [ABSTRACT FROM AUTHOR]

Background The mechanical thrombectomy (MT) for endovascular clot retrieval has dramatically improved successful revascularization and clinical outcome in selected acute stroke patients. MT is typically performed via a transfemoral approach, but catheterization of the occluded vessel can be problematic in cases of extensive vessel tortuosity. We describe a case of MT with the ‘ADAPT’ technique by direct carotid access due to an inability to catheterize the ICA by a transfemoral approach for acute cerebral ischemia in the setting of left MCA occlusion. Excellent angiographic and good clinical results were obtained without any complications. Case report An 80-year-old woman was admitted with a stroke by occlusion of the left MCA, with an NIHSS: 11, and an ASPECT: 7 in the CT. Under sedation a transfemoral angiography was performed, but after multiple attempts, it was impossible to make a stable catheterization of the left CCA. A transcervical approach was pursued. With ultrasound guidance the CCA was catheterized. Using the ‘ADAPT’ technique, we performed a successful MT. Post-procedure angiography (at 14 minutes) demonstrated recanalization of the entire left MCA (TICI: 3), without complications. The carotid access point was closed with a percutaneous closure. Control TC at 24 h showed a slight hypodensity in the left lenticular nucleus, and loss of gray-white matter differentiation in the adjacent cortex. Neurologically, the patient presented with progressive improvement. At discharge, she had an NIHSS: 0, mRS: 0 and Barthel: 100. Conclusions MT by direct carotid access is an effective alternative technique in those cases where it is not accessible by a transfemoral approach. [ABSTRACT FROM AUTHOR]

Rationale The risk of recurrence following a stroke or transient ischemic attack is high, especially immediately after the event. Hypothesis Because two antiplatelet agents are superior to one in patients with non-cardioembolic events, more intensive treatment might be even more effective. Sample size estimates The sample size of 4100 patients will allow a shift to less recurrence, and less severe recurrence, to be detected (odds ratio 0·68) with 90% power at 5% significance. Methods and design Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke ( ISRCTN47823388) is comparing the safety and efficacy of intensive (combined aspirin, clopidogrel, and dipyridamole) vs. guideline antiplatelet therapy, both given for one-month. This international collaborative parallel-group prospective randomized open-label blinded-end-point phase III trial plans to recruit 4100 patients with acute ischemic stroke or transient ischemic attack. Randomization and data collection are performed over a secure Internet site with real-time data validation and concealment of allocation. Outcomes, serious adverse events, and neuroimaging are adjudicated centrally with blinding to treatment allocation. Study outcome The primary outcome is stroke recurrence and its severity ('ordinal recurrence' based on modified Rankin Scale) at 90 days, with masked assessment centrally by telephone. Secondary outcomes include vascular events, functional measures (disability, mood, cognition, quality of life), and safety (bleeding, death, serious adverse events). Discussion The trial has recruited more than 50% of its target sample size (latest number: 2399) and is running in 104 sites in 4 countries. One-third of patients presented with a transient ischemic attack. [ABSTRACT FROM AUTHOR]

Background Limited studies exist on the outcome of thrombolytic therapy of acute ischemic stroke patients outside of clinical trials. Aim To assess the possible risk factors associated with in-hospital death and symptomatic intracerebral hemorrhage among patients who received intravenous tissue plasminogen activator. Methods A total of 7193 patients with a clinical diagnosis of acute ischemic stroke and a documented National Institutes of Health Stroke Scale score were treated with intravenous tissue plasminogen activator within 4·5 hours of time last known to be well. Generalized estimating equations modeling was used to assess the associations of in-hospital death and symptomatic intracerebral hemorrhage with clinical characteristics. Results Among 7193 patients treated with intravenous tissue plasminogen activator, 516 (7·2%) died during hospitalization. Factors associated with in-hospital death were older age, male gender, National Institutes of Health Stroke Scale score, history of myocardial infarction or coronary artery disease, and history of nonvalvular atrial fibrillation. Increasing age, higher National Institutes of Health Stroke Scale score, and history of dyslipidemia were associated with symptomatic intracerebral hemorrhage. There was no difference in the rates of in-hospital death or symptomatic intracerebral hemorrhage among patients treated with intravenous tissue plasminogen activator within three-hours of time last known to be well and those treated between three and 4·5 hours after this time. Conclusions In this study of acute ischemic stroke patients, older age, male gender, National Institutes of Health Stroke Scale score, history of myocardial infarction or coronary artery disease, and history of atrial fibrillation were associated with increased in-hospital death among patients receiving intravenous tissue plasminogen activator. Among patients treated with intravenous tissue plasminogen activator, in-hospital mortality and symptomatic intracerebral hemorrhage rates were similar between those treated within three-hours of time last known to be well and those treated between three and 4·5 hours after this time. [ABSTRACT FROM AUTHOR]

Background Neuro Thera Effectiveness and Safety Trials ( NEST) 1 and 2 have demonstrated safety of transcranial laser therapy ( TLT) for human treatment in acute ischemic stroke. NEST 1 study suggested efficacy of TLT but the following NEST 2, despite strong signals, missed reaching significance on its primary efficacy endpoint. In order to assess efficacy in a larger cohort, a pooled analysis was therefore performed. Methods The two studies were first compared for heterogeneity, and then a pooled analysis was performed to assess overall safety and efficacy, and examined particular subgroups. The primary endpoint for the pooled analysis was dichotomized modified Rankin scale (mRS) 0-2 at 90 days. Results Efficacy analysis for the intention-to-treat population was based on a total of 778 patients. Baseline characteristics and prognostic factors were balanced between the two groups. The TLT group ( n = 410) success rate measured by the dichotomized 90-day m RS was significantly higher compared with the sham group ( n = 368) ( P = 0·003, OR: 1·67, 95% CI: 1·19-2·35). The distribution of scores on the 90-day m RS was significantly different in TLT compared with sham ( P = 0·0005 Cochran- Mantel- Haenszel). Subgroup analysis identified moderate strokes as a predictor of better treatment response. Conclusions This pooled analysis support the likelihood that transcranial laser therapy is effective for the treatment of acute ischemic stroke when initiated within 24 h of stroke onset. If ultimately confirmed, transcranial laser therapy will change management and improve outcomes of far more patients with acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Background Elevated blood pressure following acute stroke is common, and yet early antihypertensive treatment is controversial. ACCESS suggested a beneficial effect of the angiotensin receptor blocker candesartan in the acute phase of stroke, but these findings need to be confirmed in new, large trials. Aims and design The Scandinavian Candesartan Acute Stroke Trial is an international randomised, placebo-controlled, double-blind trial of candesartan in acute stroke. We plan to recruit 2500 patients presenting within 30 h of stroke (ischaemic or haemorrhagic) and with systolic blood pressure ≥140 mmHg. The recruited patients are randomly assigned to candesartan or placebo for 7-days (doses increasing from 4 to 16 mg once daily). Randomisation is performed centrally via a secure web interface. The follow-up period is 6-months. Patients are included from the following nine North-European countries: Norway, Sweden, Denmark, Belgium, Germany, Poland, Lithuania, Estonia and Finland. Study outcomes There are two co-primary effect variables: • Functional status at 6-months, measured by the modified Rankin Scale, and • vascular death, myocardial infarction or stroke during the first 6-months. Secondary outcome variables: Secondary effect variables include • the Barthel index (functional status) • EuroQol (quality of life) and • Mini-mental state examination (cognition) at 6-months • Health economic costs during the first 6-months Funding The Scandinavian Candesartan Acute Stroke Trial receives basic funding from Norwegian health authorities. AstraZeneca supplies the trial drugs, and AstraZeneca and Takeda support the trial with limited, unrestricted grants. Summary The Scandinavian Candesartan Acute Stroke Trial is the first large trial of angiotensin receptor blockers in patients with elevated blood pressure and acute stroke, and aims to answer whether treatment with angiotensin receptor blockers is beneficial for this indication. [ABSTRACT FROM AUTHOR]

Rationale Cervical artery dissection is an important cause of stroke in the young. It can present with local symptoms or stroke/transient ischaemic attacks. Following presentation there is a risk of stroke, particularly in the first month following presentation. The mechanism of stroke is believed to be thromboembolic in the majority of cases. Many clinicians anticoagulate patients with cervical dissection for 3–6 months. This is not evidence based and is supported by a paucity of data and no data from randomised control trials. Aims CADISS is a prospective multicentre randomised-controlled trial in acute (within 7 days of onset) carotid and vertebral artery dissection. Intracerebral artery dissection is excluded. Design Patients are randomised to antiplatelet therapy (aspirin, dipyridamole or clopidogrel alone or in dual combination) or anticoagulation therapy [heparin followed by warfarin aiming for an International Normalised Ratio (INR) in the range 2–3] for at least 3 months. Treatment is open-label. Study outcome The primary end-point is ipsilateral stroke or death within 3 months from randomisation. Secondary end-points include any TIA or stroke, major bleeding and presence of residual stenosis at 3 months (>50%). All neuroimaging and serious adverse events will be adjudicated blinded to treatment. An initial feasibility phase of 250 subjects will allow us to determine whether •there are sufficient clinical end-points to provide the power to determine a treatment effect and •adequate numbers of patients can be recruited. The feasibility phase will be continued into a fully powered definitive treatment trial. Initial power calculations based on limited natural history data suggest a sample size of approximately 3000. Sample size calculations will be refined once the frequency of outcome events during the feasibility phase is known. [ABSTRACT FROM AUTHOR]