Effect of Sex on Outcomes of Mechanical Thrombectomy in Basilar Artery Occlusion: A Multicentre Cohort Study.

INTRODUCTION: Identifying differences in outcome of basilar artery occlusion (BAO) between males and females may be useful in aiding clinical management. Recent studies have demonstrated widespread underrepresentation of women in acute stroke clinical trials. This international multicentre study aimed to determine sex differences in outcome after mechanical thrombectomy (MT) for patients with acute BAO. METHODS: We performed a retrospective analysis of consecutive patients with BAO who had undergone MT in seven stroke centres across five countries (Singapore, Taiwan, United Kingdom, Sweden, and Germany), between 2015 and 2020. Primary outcome was a favourable functional outcome measured by a modified Ranking Scale (mRS) of 0-3 at 90 days. Secondary outcomes were mRS 0-3 upon discharge, mortality, symptomatic intracranial haemorrhage (sICH) and subarachnoid haemorrhage (SAH). RESULTS: Among the 322 patients who underwent MT, 206 (64.0%) patients were male and 116 (36.0%) were female. Females were older than males (mean ± SD 70.9 ± 14.3 years vs. 65.6 ± 133.6 years; p = 0.001) and had higher rates of atrial fibrillation (38.9% vs. 24.2%; p = 0.012). Time from groin puncture to reperfusion was shorter in females than males (mean ± SD 57.2 ± 37.2 min vs. 71.1 ± 50.9 min; p = 0.021). Despite these differences, primary and secondary outcome measures were similar in females and males, with comparable rates of favourable 90-day mRS scores (mean ± SD 46 ± 39.7 vs. 71 ± 34.5; OR = 1.20; 95% confidence interval [CI] = 0.59-2.43; p = 0.611), favourable discharge mRS scores (mean ± SD 39 ± 31.6 vs. 43 ± 25.9; OR = 1.38; 95% CI = 0.69-2.78; p = 0.368) and in-hospital mortality (mean ± SD 30 ± 25.9 vs. 47 ± 22.8; OR = 1.15; 95% CI = 0.55-2.43; p = 0.710. Rates of complications such as sICH (mean ± SD 5 ± 4.3 vs. 9 ± 4.4; OR = 0.46; 95% CI = 0.08-2.66; p = 0.385) and SAH (mean ± SD 4 ± 3.4 vs. 5 ± 2.4; OR = 0.29; 95% CI = 0.03-3.09; p = 0.303) comparably low in both groups. CONCLUSION: Females achieved comparable functional outcomes compared with males after undergoing MT for BAO acute ischemic stroke.

Effect of frailty on outcomes of endovascular treatment for acute ischaemic stroke in older patients.

BACKGROUND: frailty has been shown to be a better predictor of clinical outcomes than age alone across many diseases. Few studies have examined the relationship between frailty, stroke and stroke interventions such as endovascular thrombectomy (EVT). OBJECTIVE: we aimed to investigate the impact of frailty measured by clinical frailty scale (CFS) on clinical outcomes after EVT for acute ischemic stroke (AIS) in older patients ≥70 years. METHODS: in this retrospective cohort study, we included all consecutive AIS patients age ≥ 70 years receiving EVT at a single comprehensive stroke centre. Patients with CFS of 1-3 were defined as not frail, and CFS > 3 was defined as frail. The primary outcome was modified Rankin Score (mRS) at 90 days. The secondary outcomes included duration of hospitalisation, in-hospital mortality, carer requirement, successful reperfusion, symptomatic intracranial haemorrhage and haemorrhagic transformation. RESULTS: a total of 198 patients were included. The mean age was 78.1 years and 52.0% were female. Frail patients were older, more likely to be female, had more co-morbidities. CFS was significantly associated with poor functional outcome after adjustment for age, NIHSS and time to intervention (adjusted odds ratio [aOR] 1.54, 95% confidence interval [CI] 1.04-2.28, P = 0.032). There was trend towards higher mortality rate in frail patients (frail: 18.3%; non-frail: 9.6%; P = 0.080). There were no significant differences in other secondary outcomes except increased carer requirement post discharge in frail patients (frail: 91.6%; non-frail: 72.8%; P = 0.002). CONCLUSIONS: frailty was associated with poorer functional outcome at 90 days post-EVT in patients ≥ 70 years.

Transcriptome analysis reveals intermittent fasting-induced genetic changes in ischemic stroke.

Genetic changes due to dietary intervention in the form of either calorie restriction (CR) or intermittent fasting (IF) are not reported in detail until now. However, it is well established that both CR and IF extend the lifespan and protect against neurodegenerative diseases and stroke. The current research aims were first to describe the transcriptomic changes in brains of IF mice and, second, to determine whether IF induces extensive transcriptomic changes following ischemic stroke to protect the brain from injury. Mice were randomly assigned to ad libitum feeding (AL), 12 (IF12) or 16 (IF16) h daily fasting. Each diet group was then subjected to sham surgery or middle cerebral artery occlusion and consecutive reperfusion. Mid-coronal sections of ipsilateral cerebral tissue were harvested at the end of the 1 h ischemic period or at 3, 12, 24 or 72 h of reperfusion, and genome-wide mRNA expression was quantified by RNA sequencing. The cerebral transcriptome of mice in AL group exhibited robust, sustained up-regulation of detrimental genetic pathways under ischemic stroke, but activation of these pathways was suppressed in IF16 group. Interestingly, the cerebral transcriptome of AL mice was largely unchanged during the 1 h of ischemia, whereas mice in IF16 group exhibited extensive up-regulation of genetic pathways involved in neuroplasticity and down-regulation of protein synthesis. Our data provide a genetic molecular framework for understanding how IF protects brain cells against damage caused by ischemic stroke, and reveal cellular signaling and bioenergetic pathways to target in the development of clinical interventions.

Left Atrial Volume Index Predicts New-Onset Atrial Fibrillation and Stroke Recurrence in Patients with Embolic Stroke of Undetermined Source.

INTRODUCTION: It is unclear which surrogate of atrial cardiopathy best predicts the risk of developing a recurrent ischemic stroke in embolic stroke of undetermined source (ESUS). Left atrial diameter (LAD) and LAD index (LADi) are often used as markers of left atrial enlargement in current ESUS research, but left atrial volume index (LAVi) has been found to be a better predictor of cardiovascular outcomes in other patient populations. OBJECTIVE: We aim to compare the performance of LAVi, LAD, and LADi in predicting the development of new-onset atrial fibrillation (AF) and stroke recurrence in ESUS. METHODS: Between October 2014 and October 2017, consecutive patients diagnosed with ESUS were followed for new-onset AF, ischemic stroke recurrence, and a composite outcome of occult AF and stroke recurrence. LAVi and LADi were measured by transthoracic echocardiogram; "high" LAVi was defined as ≥35 mL/m2 in accordance with American Society of Echocardiography guidelines. RESULTS: 185 ischemic stroke patients with ESUS were recruited and followed for a median duration of 2.1 years. Increased LAVi was associated with new-onset AF detection (aOR 1.08; 95% CI 1.03-1.14; p = 0.003) and stroke recurrence (aOR 1.05; 95% CI 1.01-1.10; p = 0.026). Patients with "high" LAVi had a higher likelihood of developing a composite of AF detection and stroke recurrence (HR 3.45; 95% CI 1.55-7.67; p = 0.002). No significant association was observed between LADi and either occult AF or stroke recurrence. CONCLUSIONS: LAVi is associated with new-onset AF and stroke recurrence in ESUS patients and may be a better surrogate of atrial cardiopathy.

Impact of the COVID-19 pandemic on hyperacute stroke treatment: experience from a comprehensive stroke centre in Singapore.

The Coronavirus disease 2019 (COVID-19) pandemic is rapidly evolving and affecting healthcare systems across the world. Singapore has escalated its alert level to Disease Outbreak Response System Condition (DORSCON) Orange, signifying severe disease with community spread. We aimed to study the overall volume of AIS cases and the delivery of hyperacute stroke services during DORSCON Orange. This was a single-centre, observational cohort study performed at a comprehensive stroke centre responsible for AIS cases in the western region of Singapore, as well as providing care for COVID-19 patients. All AIS patients reviewed as an acute stroke activation in the Emergency Department (ED) from November 2019 to April 2020 were included. System processes timings, treatment and clinical outcome variables were collected. We studied 350 AIS activation patients admitted through the ED, 206 (58.9%) pre- and 144 during DORSCON Orange. Across the study period, number of stroke activations showed significant decline (p = 0.004, 95% CI 6.513 to - 2.287), as the number of COVID-19 cases increased exponentially, whilst proportion of activations receiving acute recanalization therapy remained stable (p = 0.519, 95% CI - 1.605 to 2.702). Amongst AIS patients that received acute recanalization therapy, early neurological outcomes in terms of change in median NIHSS at 24 h (-4 versus -4, p = 0.685) were largely similar between the pre- and during DORSCON orange periods. The number of stroke activations decreased while the proportion receiving acute recanalization therapy remained stable in the current COVID-19 pandemic in Singapore.

Point-of-Care Surface Plasmon Resonance Biosensor for Stroke Biomarkers NT-proBNP and S100ß Using a Functionalized Gold Chip with Specific Antibody.

Surface-plasmon-resonance (SPR) is a quantum-electromagnetic phenomenon arising from the interaction of light with free electrons at a metal-dielectric interface. At a specific angle/wavelength of light, the photon's energy is transferred to excite the oscillation of the free electrons on the surface. A change in the refractive-index (RI) may occur, which is influenced by the analyte concentration in the medium in close contact with the metal surface. SPR has been widely used for the detection of gaseous, liquid, or solid samples. In this study, a functionalized specific SPR chip was designed and used in a novel point-of-care SPR module (PhotonicSys SPR H5) for the detection of the stroke biomarkers NT-proBNP and S100ß. These biomarkers have proven to be good for stroke diagnosis, with sensitivity and specificity of >85%. Specific detection was done by binding a biomolecular-recognizing antibody onto the Au SPR-chip. Detection was tested in water and plasma samples. NT-proBNP and S100ß were detected in a range of concentrations for stroke, from 0.1 ng/mL to 10 ng/mL. The RI of the blank plasma samples was 1.362412, and the lowest concentration tested for both biomarkers showed a prominent shift in the RI signal (0.25 ng/mL NT-proBNP (1.364215) and S100ß (1.364024)). The sensor demonstrated a clinically relevant limit-of-detection of less than ng/mL.

Improvement in Door-to-Needle Time in Patients with Acute Ischemic Stroke via a Simple Stroke Activation Protocol.

BACKGROUND: In acute ischemic stroke (AIS), treatment with intravenous tissue-type plasminogen activator (IV-tPA) is time-sensitive. All stroke centers make continual efforts to reduce door-to-needle time (DNT) with varying success. We present the impact of modifications to our stroke activation protocol on DNT. METHODS: We included 404 consecutive patients with AIS receiving IV-tPA between January 2014 and December 2016. First changes in stroke activation protocol were made in March 2015 in the form of prenotification by paramedics, direct transfer from ambulance to computed tomography (CT) scanner, and rapid en route neurological assessment by an emergency physician and neurologist. In March 2016, a second amendment was made where a stroke nurse accompanied the patient to expedite various steps in the treatment pathway, including endovascular treatment in eligible cases. RESULTS: Both protocol amendments resulted in improvement in DNT and door-to-CT time from 84 ± 47 minutes before intervention to 69 ± 33 minutes after protocol amendment 1 to 59 ± 37 minutes after protocol amendment 2. In particular, the second amendment (144 patients) showed significant shortening of DNT compared with the 137 patients before (59 ± 37 minutes versus 69 ± 33 minutes, P = .020), with a higher percentage achieving the target of 60 minutes (68.1% versus 48.2%, P < .001). This finding was attributed to a reduction in both door-to-CT time and CT-to-needle time. This improvement remained consistent over subsequent months. CONCLUSIONS: The application of a simple systems-based, multidisciplinary stroke activation protocol may help in significant reduction in DNT. Encouraging increased patient ownership by stroke nurses appeared to be a promising approach for timely administration of definitive acute therapies.

Good Intracranial Collaterals Trump Poor ASPECTS (Alberta Stroke Program Early CT Score) for Intravenous Thrombolysis in Anterior Circulation Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: In acute ischemic stroke, large early infarct size estimated by the Alberta Stroke Program Early CT Score (ASPECTS) is associated with poorer outcomes and is a relative contraindication for recanalization therapies. The state of the intracranial collateral circulation influences the functional outcome and may be a variable to consider before thrombolysis. We evaluated the prognostic effect of the collateral circulation in patients with thrombolyzed acute ischemic stroke who have large early infarct sizes as indicated by low ASPECTS. MATERIALS AND METHODS: Patients with anterior circulation acute ischemic stroke who received a computed tomographic angiogram and subsequent treatment with intravenous tissue-type plasminogen activator from 2010 to 2013 were studied. Two independent neuroradiologists determined their ASPECTS. We stratified patients using ASPECTS into 2 groups: large volume infarcts (ASPECTS≤7 points) and small volume infarcts (ASPECTS 8-10). In addition, we evaluated a third group with very large volume infarcts (ASPECTS≤5 points). We then analyzed the 3 subgroups using the Maas, Tan, and ASPECTS-collaterals grading systems of the computed tomographic angiogram intracranial collaterals. Good outcomes were defined by modified Rankin Scale score of 0 to 2 at 3 months. RESULTS: A total of 300 patients were included in the final analysis. For patients with very large volume infarcts (ASPECTS≤5 points), univariable analysis showed that younger age, male sex, lower National Institute of Health Stroke Scale (NIHSS), lower systolic blood pressure, and good collaterals by Maas, Tan, or ASPECTS-collaterals grading were predictors of good outcomes. On multivariate analysis, younger age (odds ratio, 0.93; 95% confidence interval, 0.89-0.97; P=0.002) and good collaterals by ASPECTS-collaterals system (odds ratio, 1.34; 95% confidence interval, 1.15-1.57; P<0.001) were associated with good outcomes. CONCLUSIONS: In patients with large and very large volume infarcts, good collaterals as measured by the ASPECTS-collaterals system is associated with improved outcomes and can help select patients for intravenous thrombolysis.

Intravenous Thrombolysis for Acute Ischemic Stroke due to Cervical Internal Carotid Artery Occlusion.

BACKGROUND: Internal carotid artery (ICA) occlusions are poorly responsive to intravenous thrombolysis with tissue plasminogen activator (IV-tPA) in acute ischemic stroke (AIS). Most study populations have combined intracranial and extracranial ICA occlusions for analysis; few have studied purely cervical ICA occlusions. We evaluated AIS patients with acute cervical ICA occlusion treated with IV-tPA to identify predictors of outcomes. METHODS: We studied 550 consecutive patients with AIS who received IV-tPA and identified 100 with pure acute cervical ICA occlusion. We evaluated the associations of vascular risk factors, National Institutes of Health Stroke Scale (NIHSS) score, and leptomeningeal collateral vessel status via 3 different grading systems, with functional recovery at 90 days, mortality, recanalization of the primary occlusion, and symptomatic intracranial hemorrhage (SICH). Modified Rankin Scale score 0-1 was defined as an excellent outcome. RESULTS: The 100 patients had mean age of 67.8 (range 32-96) and median NIHSS score of 19 (range 4-33). Excellent outcomes were observed in 27% of the patients, SICH in 8%, and mortality in 21%. Up to 54% of the patients achieved recanalization at 24 hours. On ordinal regression, good collaterals showed a significant shift in favorable outcomes by Maas, Tan, or ASPECTS collateral grading systems. On multivariate analysis, good collaterals also showed reduced mortality (OR .721, 95% CI .588-.888, P = .002) and a trend to less SICH (OR .81, 95% CI .65-1.007, P = .058). Interestingly, faster treatment was also associated with favorable functional recovery (OR 1.028 per minute, 95% CI 1.010-1.047, P = .001). CONCLUSIONS: Improved outcomes are seen in patients with early acute cervical ICA occlusion and better collateral circulation. This could be a valuable biomarker for decision making.

External validation of the Boston Acute Stroke Imaging Scale and M1-BASIS in thrombolyzed patients.

BACKGROUND AND PURPOSE: Radiological findings play an essential role in therapeutic decision making and prognostication in acute ischemic stroke (AIS). The Boston Acute Stroke Imaging Scale (BASIS) and Middle Cerebral Artery-BASIS (M1-BASIS) methodologies are rapid purely radiological instruments and easily applicable for patients with AIS. We validated these methods in patients with AIS treated with intravenous tissue-type plasminogen activator. METHODS: For BASIS, patients were labeled as having major stroke if there was occlusion of distal internal carotid artery, proximal (both M1 and M2 segments) of middle cerebral artery or the basilar artery, or an Alberta Stroke Program Early CT Score≤7. M1-BASIS differs from BASIS by classifying AIS patients with M2 occlusion as a minor stroke. We evaluated these classification systems for predicting functional outcomes (modified Rankin Scale score 0-1) at 3 months. RESULTS: Two hundred sixty-five consecutive AIS patients treated with intravenous tissue-type plasminogen activator were included. On multivariate analysis, younger age (odds ratio, 1.039, 95% confidence interval, 1.009-1.070; P=0.011), lower National Institutes of Health Stroke Scale score (odds ratio, 1.140; 95% confidence interval, 1.073-1.210; P<0.001), and minor stroke by M1-BASIS (odds ratio, 2.376; 95% confidence interval, 1.047-5.393; P=0.039) were independent predictors of good functional outcome. When compared with National Institutes of Health Stroke Scale, the receiver operating characteristic curves for both BASIS (area under the curve, 0.721) and M1-BASIS (area under the curve, 0.795) correlated well with clinical severity scores. M1-BASIS has an additive effect with the National Institutes of Health Stroke Scale score to predict good outcomes. CONCLUSIONS: The purely radiological M1-BASIS correlates well with the clinical severity of stroke and can be a reliable prognostication tool in thrombolyzed AIS patients. This system might find an important place in the current era of telestroke.

Safety of intravenous thrombolysis for ischemic stroke in patients treated with warfarin.

OBJECTIVE: Controversy surrounds the safety of intravenous (IV) tissue plasminogen activator (tPA) in ischemic stroke patients treated with warfarin. The European tPA license precludes its use in anticoagulated patients altogether. American guidelines accept IV tPA use with an international normalized ratio (INR) ≤ 1.7. The influence of warfarin on symptomatic intracerebral hemorrhage (SICH), arterial recanalization, and long-term functional outcome in stroke thrombolysis remains unclear. METHODS: We analyzed data from 45,074 patients treated with IV tPA enrolled in the Safe Implementation of Thrombolysis in Stroke (SITS) International Stroke Thrombolysis Register. A total of 768 patients had baseline warfarin treatment with INR ≤ 1.7. Outcome measures were SICH, arterial recanalization, mortality, and functional independence at 3 months. RESULTS: Patients on warfarin with INR ≤ 1.7 were older, had more comorbidities, and had more severe strokes compared to patients without warfarin. There were no significant differences between patients with and without warfarin in SICH rates (adjusted odds ratio [aOR] = 1.23, 95% confidence interval [CI] = 0.72-2.11 per SITS-MOST; aOR = 1.26, 95% CI = 0.82-1.70 per European Cooperative Acute Stroke Study II) after adjustment for age, stroke severity, and comorbidities. Neither did warfarin independently influence mortality (aOR = 1.05, 95% CI = 0.83-1.35) or functional independence at 3 months (aOR = 1.01, 95% CI = 0.81-1.24). Arterial recanalization by computed tomography/magnetic resonance angiography trended higher in warfarin patients (62% [37 of 59] vs 55% [776/1,475], p = 0.066). Recanalization approximated by disappearance at 22 to 36 hours of a baseline hyperdense middle cerebral artery sign was increased (63% [124 of 196] vs 55% [3,901 of 7,099], p = 0.022). INTERPRETATION: Warfarin treatment with INR ≤ 1.7 did not increase the risk for SICH or death, and had no impact on long-term functional outcome in patients treated with IV tPA for acute ischemic stroke.

Thrombolysis outcomes among obese and overweight stroke patients: an age- and National Institutes of Health Stroke Scale-matched comparison.

BACKGROUND: Whether obese and overweight stroke patients respond differently to intravenous thrombolysis is unclear. The purpose of this study is to determine the influence of obesity and risk components of metabolic syndrome to stroke recovery in patients undergoing intravenous thrombolysis. METHODS: Outcomes after recombinant tissue plasminogen activator treatment were compared between obese (body mass index [BMI] >30 kg/m(2)), overweight (BMI 25-30 kg/m(2)), and normal weight (BMI <25 kg/m(2)) patients. The association between BMI, risk components of the metabolic syndrome, and dose of recombinant tissue plasminogen activator per kilogram of body weight to stroke outcomes were assessed in a multivariable model. RESULTS: A total of 169 patients (mean age 75 years; baseline National Institutes of Health Stroke Scale score 11) were included. No differences in the frequency of symptomatic intracranial hemorrhage and poor functional recovery were observed among obese, overweight, and normal weight patients. A linear trend toward worse stroke recovery was observed in patients with a greater number of metabolic risk components (P for trend .043). By contrast, there were no significant associations between the number of risk components of metabolic syndrome with respect to symptomatic intracranial hemorrhage. Using stepwise regression analyses, age, baseline stroke severity, and the number of risk components of the metabolic syndrome accounted for 52% variation in functional recovery after intravenous thrombolysis. CONCLUSIONS: Acute stroke outcomes do not differ between obese and overweight patients undergoing intravenous thrombolysis. The number of metabolic risk components contributes more significantly to functional recovery following intravenous thrombolysis.

Internal cerebral vein asymmetry on follow-up brain computed tomography after intravenous thrombolysis in acute anterior circulation ischemic stroke is associated with poor outcome.

BACKGROUND: Identifying early predictors of functional outcome after acute ischemic stroke (AIS) is important for planning rehabilitation strategies. Internal cerebral veins (ICV) drain deep parts of brain, run parallel to each other, and consistently seen on computed tomography angiography (CTA). Even minor asymmetry in their filling can be identified. We hypothesized that venous drainage would be impaired in patients with acute occlusion of internal carotid artery or middle cerebral artery. Because systemic thrombolysis can alter the vascular findings, we evaluated the relationship between ICV asymmetry on follow-up CTA and functional outcome. METHODS: Consecutive AIS patients treated with intravenous thrombolysis between 2007 and 2010 were included. ICV asymmetry was assessed by 2 independent blinded stroke neurologists/neuroradiologists. Functional outcome was assessed by the modified Rankin Scale (mRS) at 3 months, dichotomized as good (0-1) and poor (2-6). Data were analyzed for predictors of functional outcome. RESULTS: Of 2238 patients with AIS, 226 (10.1%) anterior circulation AIS patients received intravenous thrombolysis. The median age was 65 years (range 19-92), 44% were men, and median National Institutes of Health Stroke Scale (NIHSS) score was 16 points (range 4-32). Hypertension was the commonest risk factor in 173 (76.5%) patients, whereas 78 (34.5%) had atrial fibrillation. ICV asymmetry on follow-up CTA was assessed in 103 (45.5%) patients. Admission NIHSS score (odds ratio [OR] 1.07; 95% confidence interval [CI] 1.079-1.201, P = .046), change in NIHSS score during first 24 hours (OR .737; 95% CI .672-.807, P < .0001), and ICV asymmetry on follow-up CTA (OR 20.3; 95% CI 4.67-52.07, P < .0001) independently predicted poor outcome at 3 months. CONCLUSIONS: ICV asymmetry on follow-up CTA after intravenous thrombolysis is an early predictor of poor functional outcome.

Low HALP (Hemoglobin, Albumin, Lymphocyte, and Platelet) Score Increases the Risk of Post-Stroke Cognitive Impairment: A Multicenter Cohort Study.

Objective: The HALP (hemoglobin, albumin, lymphocyte, and platelet) score is a novel indicator that measures systemic inflammation and nutritional status that has not been correlated with the risk of post-stroke cognitive impairment in patients with acute ischemic stroke or transient ischemic attack (TIA). Methods: Study participants were recruited from 40 stroke centers in China. The HALP score was derived using a weighted sum of hemoglobin, albumin, lymphocytes and platelets, and study participants were categorized into 4 groups of equal sizes based on quartiles cutoffs of the HALP score. The Montreal Cognitive Assessment (MoCA)-Beijing Cognitive Assessment Scale (MoCA-Beijing) was performed at 2 weeks and 12 months following stroke onset. Post-stroke cognitive impairment was considered in patients with MoCA-Beijing≤22. Multiple logistic regression methods were employed to evaluate the relationship between the HALP score and the subsequent risk of developing post-stroke cognitive impairment. Results: The study population comprised 1022 patients (mean age 61.6±11.0 years, 73% men). The proportion of individuals with MoCA-Beijing≤22 at 2 weeks was 49.2% and 32.4% at one year. Patients in the lowest quartile of HALP score (<36.56) were observed to harbor the highest risk of post-stroke cognitive impairment at 12 months post-stroke/TIA compared to those in the highest quartile (odds ratio=1.59, 95% CI=1.07-2.37, p=0.022), and lower domain scores for executive function, naming, and attention. There were no statistically significant differences between patients in the different quartiles of HALP score and HALP score at 2 weeks post-stroke/TIA. Conclusion: The HALP score is a simple score that could stratify the risk of post-stroke cognitive impairment in stroke/TIA patients to facilitate early diagnosis and interventions.

Left Ventricular Diastolic Dysfunction Is Associated with Poor Functional Outcomes after Endovascular Thrombectomy.

INTRODUCTION: With the advent of endovascular thrombectomy (ET), patients with acute ischaemic strokes (AIS) with large vessel occlusion (LVO) have seen vast improvements in treatment outcomes. Left ventricular diastolic dysfunction (LVDD) has been shown to herald poorer prognosis in conditions such as myocardial infarction. However, whether LVDD is related to functional recovery and outcomes in ischaemic stroke remains unclear. We studied LVDD for possible relation with clinical outcomes in patients with LVO AIS who underwent ET. METHODS: We studied a retrospective cohort of 261 LVO AIS patients who had undergone ET at a single comprehensive stroke centre and correlated LVDD to short-term mortality (in-hospital death) as well as good functional recovery defined as modified Rankin Scale of 0-2 at 3 months. RESULTS: The study population had a mean age of 65-years-old and were predominantly male (54.8%). All of the patients underwent ET with 206 (78.9%) achieving successful reperfusion. Despite this, 25 (9.6%) patients demised during the hospital admission and 149 (57.1%) did not have good function recovery at 3 months. LVDD was present in 82 (31.4%) patients and this finding indicated poorer outcomes in terms of functional recovery at 3 months (OR 2.18, 95% CI 1.04-4.54, p = 0.038) but was not associated with increased in-hospital mortality (OR 2.18, 95% CI 0.60-7.99, p = 0.240) after adjusting for various confounders. CONCLUSION: In addition to conventional echocardiographic indices such as left ventricular ejection fraction, LVDD may portend poorer outcomes after ET, and this relationship should be investigated further.

Augmentation of 5-lipoxygenase activity and expression during dengue serotype-2 infection.

BACKGROUND: Leukotriene B4, a 5-lipoxygenase product of arachidonic acid with potent chemotactic effects on neutrophils, has not been assessed in dengue patients. In this study, plasma leukotriene B4 and serum high-sensitivity C-reactive protein levels were determined in adult patients during the febrile, convalescent and defervescent stages of dengue serotype-2 (DENV-2) infection, and compared with those of age-matched healthy and non-dengue febrile subjects. In vitro studies were performed to examine the effects of live and heat-inactivated DENV-2 on the activities and expression of 5-lipoxygenase in human neutrophils. RESULTS: Plasma leukotriene B4 was elevated during the febrile stages of dengue infection compared to levels during convalescence and in study controls. Plasma leukotriene B4 also correlated with serum high-sensitivity C-reactive protein in dengue patients (febrile, r = 0.91, p < 0.001; defervescence, r = 0.87, p < 0.001; convalescence, r = 0.87, p < 0.001). Exposure of human neutrophils to DENV-2 resulted in a significant rise in leukotriene B4; the extent of increase, however, did not differ between exposure to live and heat-inactivated DENV-2. Pre-incubation of either live or heat-inactivated DENV-2 resulted in reduced leukotriene B4 release by neutrophils, indicating that contact with dengue antigens (and not replication) triggers the neutrophil response. Production of leukotriene B4 was associated with an increase in 5-lipoxygenase expression in human neutrophils; addition of MK886 (a 5-lipoxygenase activating protein inhibitor) attenuated further increase in leukotriene B4 production. CONCLUSION: These findings provide important clinical and mechanistic data on the involvement of 5-lipoxygenase and its metabolites in dengue infection. Further studies are needed to elucidate the therapeutic implications of these findings.

Dosing of tissue plasminogen activator often differs from 0.9 mg/kg, but does not affect the outcome.

BACKGROUND: The safety and efficacy of low- and high-dose intravenous tissue plasminogen activator (t-PA) for the treatment of acute ischemic stroke are poorly understood. In this multicenter study, we examined the relationships between different doses of t-PA and outcome. METHODS: Between 2006 and 2010, patients were enrolled if they were treated with t-PA on the basis of estimated body weight and on the subsequent availability of actual body weight. Based on the actual weight, patients were divided into lower (<0.85 mg/kg), standard (0.85-0.95 mg/kg), and higher (>0.95 mg/kg) t-PA dose groups. Differences in the outcomes of these groups were compared in terms of functional recovery (modified Rankin Scale [mRS] 0-1) at 3 months and the incidence of parenchymal hemorrhages on follow-up computed tomographic scans. RESULTS: This cohort study included 272 patients: 171 (63%) patients received the standard t-PA dose, 62 (23%) a lower dose, and 39 (14%) a higher dose. At 3 months, 51% of the standard dose patients achieved a mRS score of 0 to 1, compared with 50% in the lower dose and 44% in the higher dose groups. Parenchymal hemorrhage occurred in 4.7%, 6.5%, and 7.7% of patients in standard, lower, and higher dose groups, respectively. Compared with standard dose groups, no significant differences in functional recovery and parenchymal hemorrhage were observed in the lower and higher dose groups. CONCLUSIONS: In clinical practice, the actual dose of t-PA often differs from the recommended dose of 0.9 mg/kg, but this has no significant impact on the outcome after t-PA treatment.

Risk factors and consequences of atrial fibrillation with rapid ventricular response in patients with ischemic stroke treated with intravenous thrombolysis.

Atrial fibrillation (AF) is associated with rapid ventricular response (RVR) that increases myocardial demand and blood pressure instability. We investigated the incidence, risk factors, and outcomes of RVR among patients with ischemic stroke receiving treatment with intravenous (IV) recombinant tissue plasminogen activator (rtPA). Consecutive patients with AF who received IV rtPA within 3 hours of symptom onset were included. Vascular risk factors, stroke characteristics, and outcome measures were compared between patients who developed RVR and those who did not. Eighty patients with AF (mean age, 79 years; 46% men) who underwent rtPA treatment were studied. Nineteen (24%) of these patients developed RVR and were treated with IV rate-controlling medications. A bimodal pattern of distribution was observed in the occurrence of RVR, with the first peak occurring within 12 hours of stroke onset and the second peak occurring 24-48 hours after onset. Compared with the patients without RVR, those with RVR stayed a median duration of 1.2 days longer in the intensive care unit (P = .048). There were no differences in functional recovery and hemorrhagic outcomes between the patients with RVR and those without RVR. We observed a 16-hour delay in the resumption of antiarrhythmic medications (either at previous or reduced dosage) in the patients who subsequently developed RVR (median time from stroke onset, 29 hours vs 13 hours; P = .040). Our findings suggest that a delay in the resumption of rate-control medications in patients with AF may result in RVR and prolong the use of intensive care resources.

Safety of intravenous thrombolysis in acute ischemic stroke patients with saccular intracranial aneurysms.

BACKGROUND: It is not known if the presence of unruptured intracranial aneurysms can increase the risk of hemorrhage after thrombolysis for acute ischemic stroke. The goal of our study was to evaluate the risk of hemorrhage after intravenous tissue plasminogen activator in acute stroke patients with intracranial aneurysms. METHODS: This is a retrospective analysis of consecutive cases of patients with acute ischemic stroke who were treated with intravenous tissue plasminogen activator at Mayo Clinic between March 2002 and June 2011 and who were evaluated with invasive or noninvasive intracranial angiography. Univariate analyses were performed with the t, Chi-square, and Fisher exact tests where appropriate. RESULTS: Intracranial angiograms were performed in 105 patients (85 magnetic resonance angiography, 19 computed tomography angiography, and 1 catheter arteriography). The mean age of the patients was 69 ± 14 years. The mean National Institutes of Health Stroke Scale score at admission was 8 ± 5. A total of 12 incidental saccular aneurysms were found in 10 (9.5%) patients, and all 10 of these patients were white. There were no subarachnoid hemorrhages during the hospital stay in any patient with or without intracranial aneurysm. The rates of symptomatic intracranial hemorrhage and 3-month clinical outcomes were similar in patients with or without intracranial aneurysms. CONCLUSIONS: Intravenous thrombolysis was safe among our patients with acute ischemic stroke and incidental intracranial saccular aneurysm.