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BACKGROUND AND OBJECTIVES: Despite advances in the prevention of rhesus (Rh)(D) alloimmunization, alloantibodies to Rh(D) and non-Rh(D) red blood cell antigens continue to be detected in _4% of US pregnancies and can result in hemolytic disease of the fetus and newborn (HDFN). Recent reports on HDFN lack granularity and are unable to provide antibody-specific outcomes. The objective of this study was to calculate the frequency of alloimmunization in our large hospital system and summarize the outcomes based on antibody specificity, titer, and other clinical factors. METHODS: We identified all births in a 6-year period after a positive red blood cell antibody screen result during pregnancy and summarized their characteristics and outcomes. RESULTS: A total of 707 neonates were born after a positive maternal antibody screen result (3.0/1000 live births). In 31 (4%), the positive screen result was due to rhesus immune globulin alone. Of the 676 neonates exposed to alloantibodies, the direct antibody test (DAT) result was positive, showing antigen-positivity and evidence of HDFN in 37% of those tested. Neonatal disease was most severe with DAT-positive anti-Rh antibodies (c, C, D, e, E). All neonatal red blood cell transfusions (15) and exchange transfusions (6) were due to anti-Rh alloimmunization. No neonates born to mothers with anti-M, anti-S, anti-Duffy, anti-Kidd A, or anti-Lewis required NICU admission for hyperbilirubinemia or transfusion. CONCLUSIONS: Alloimmunization to Rh-group antibodies continues to cause a majority of the severe HDFN cases in our hospital system. In neonates born to alloimmunized mothers, a positive DAT result revealing antigen-positivity is the best predictor of anemia and hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

Ischemic stroke is the leading cause of serious long-term disability and the 5th leading cause of death in the United States. Revascularization of the occluded cerebral artery, either by thrombolysis or endovascular thrombectomy, is the only effective, clinically-approved stroke therapy. Several potentially neuroprotective agents, including glutamate antagonists, anti-inflammatory compounds and free radical scavenging agents were shown to be effective neuroprotectants in preclinical animal models of brain ischemia. However, these compounds did not demonstrate efficacy in clinical trials with human patients following stroke. Proposed reasons for the translational failure include an insufficient understanding on the cellular and molecular pathophysiology of ischemic stroke, lack of alignment between preclinical and clinical studies and inappropriate design of clinical trials based on the preclinical findings. Therefore, novel neuroprotective treatments must be developed based on a clearer understanding of the complex spatiotemporal mechanisms of ischemic stroke and with proper clinical trial design based on the preclinical findings from specific animal models of stroke. We and others have demonstrated the clinical potential for neuregulin-1 (NRG-1) in preclinical stroke studies. NRG-1 significantly reduced ischemia-induced neuronal death, neuroinflammation and oxidative stress in rodent stroke models with a therapeutic window of >13 h. Clinically, NRG-1 was shown to be safe in human patients and improved cardiac function in multisite phase II studies for heart failure. This review summarizes previous stroke clinical candidates and provides evidence that NRG-1 represents a novel, safe, neuroprotective strategy that has potential therapeutic value in treating individuals after acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Background Hyperdense cerebral artery sign (HCAS) is an imaging biomarker in acute ischemic stroke (AIS) that has been shown to be associated with various clinical outcomes and stroke etiology. While prior studies have correlated HCAS with histopathological composition of cerebral thrombus, it is unknown whether and to what extent HCAS is also associated with distinct clot protein composition. Methods Thromboembolic material from 24 patients with AIS were retrieved via mechanical thrombectomy and evaluated with mass spectrometry in order to characterize their proteomic composition. Presence (+) or absence (-) of HCAS on preintervention non-contrast head CT was then determined and correlated with thrombus protein signature with abundance of individual proteins calculated as a function HCAS status. Results 24 clots with 1797 distinct proteins in total were identified. 14 patients were HCAS(+) and 10 were HCAS(-). HCAS(+) were most significantly differentially abundant in actin cytoskeletal protein (P=0.002, Z=2.82), bleomycin hydrolase (P=0.007, Z=2.44), arachidonate 12-lipoxygenase (P=0.004, Z=2.60), and lysophospholipase D (P=0.007, Z=2.44), among other proteins; HCAS(-) clots were differentially enriched in soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (P=0.0009, Z=3.11), tyrosine-protein kinase Fyn (P=0.002, Z=2.84), and several complement proteins (P<0.05, Z>1.71 for all), among numerous other proteins. Additionally, HCAS(-) thrombi were enriched in biological processes involved with plasma lipoprotein and protein-lipid remodeling/assembling, and lipoprotein metabolic processes (P<0.001), as well as cellular components including mitochondria (P<0.001). Conclusions HCAS is reflective of distinct proteomic composition in AIS thrombus. These findings suggest that imaging can be used to identify mechanisms of clot formation or maintenance at the protein level, and might inform future research on thrombus biology and imaging characterization. [ABSTRACT FROM AUTHOR]

Flow diverters are a promising new tool in the neurosurgeon's arsenal for aneurysm management. We sought to quantify the trends of flow diversion in comparison to traditional endovascular coiling and surgical clip ligation techniques in the United States from 2010 to 2020 with an emphasis on aneurysm location and preferences in usage for ruptured versus unruptured aneurysms. In this large cross-sectional study, patients aged 18 and older within the MARINER database were analyzed. Descriptive characteristics were calculated for all included patients. χ2 tests were used to compare categorical variables. P values < 0.05 were statistically significant. A total of 45,542 procedures were conducted in the United States from 2010 to 2020 (clipping: 14,491; coiling: 28,840; flow diversion: 2211). The Southern United States had the largest operative volume across all 3 intervention types, closely followed by the Midwest. Aneurysms of the middle cerebral artery were mostly clipped, whereas coiling and flow diversion techniques were most utilized for anterior communicating and posterior communicating artery aneurysms. Flow diversion is growing most rapidly in the treatment of unruptured aneurysms, though there were also significant increases in usage for ruptured aneurysm treatment from 2019 to 2020. Flow diverters have gained significant traction in the treatment for both unruptured and ruptured aneurysms. In the coming years, the indications and use of flow diversion will undoubtedly grow further, but excitement over their application should be tempered by the safety and efficacy data that continues to emerge. [ABSTRACT FROM AUTHOR]

Background A thrombus in the M1 segment of the middle cerebral artery (MCA) can occlude this main stem only or extend into the M1- M2 bifurcation. The occlusion pattern may affect endovascular treatment (EVT) success, as a bifurcated thrombus may be more prone to fragmentation during retrieval. Objective To investigate whether bifurcated thrombus patterns are associated with EVT procedural and clinical outcomes. Methods Occlusion patterns of MCA thrombi on CT angiography from MR CLEAN Registry patients were classified into three groups: main stem occlusion, bifurcation occlusion extending into one M2 branch, and bifurcation occlusion extending into both M2 branches. Procedural parameters, procedural outcomes (reperfusion grade and embolization to new territory), and clinical outcomes (24- 48 hour National Institutes of Health Stroke Scale [NIHSSFU] score, change in NIHSS scores between 24 and 48 hours and baseline Δ [NIHSS], and 90- day modified Rankin Scale [mRS] scores) were compared between occlusion patterns. Results We identified 1023 patients with an MCA occlusion of whom 370 (36%) had a main stem occlusion, 151 (15%) a single branch, and 502 (49%) a double branch bifurcation occlusion. There were no statistically significant differences in retrieval method, procedure time, number of retrieval attempts, reperfusion grade, and embolization to new territory between occlusion patterns. Patients with main stem occlusions had lower NIHSSFU scores than patients with single (7 vs 11, p=0.01) or double branch occlusions (7 vs 9, p=0.04). However, there were no statistically significant differences in Δ NIHSS or in 90- day mRS scores. Conclusions In our population, EVT procedural and long- term clinical outcomes were similar for MCA bifurcation occlusions and MCA main stem occlusions. [ABSTRACT FROM AUTHOR]

Background The cost-effectiveness of endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to M2 branch occlusion remains uncertain. Objective To evaluate the cost-effectiveness of EVT compared with medical management in patients with acute stroke presenting with M2 occlusion using a decision-analytic model. Methods A decision-analytic study was performed with Markov modeling to estimate the lifetime quality-adjusted life years and associated costs of EVT-treated patients compared with no-EVT/medical management. The study was performed over a lifetime horizon with a societal perspective in the Unites States setting. Base case, one-way, two-way, and probabilistic sensitivity analyses were performed. Results EVT was the long-term cost-effective strategy in 93.37% of the iterations in the probabilistic sensitivity analysis, and resulted in difference in health benefit of 1.66 QALYs in the 65-year-old age groups, equivalent to 606 days in perfect health. Varying the outcomes after both strategies shows that EVT was more cost-effective when the probability of good outcome after EVT was only 4-6% higher relative to medical management in clinically likely scenarios. EVT remained cost-effective even when its cost exceeded US$200 000 (threshold was US$209 111). EVT was even more cost-effective for 55-year-olds than for 65-year-old patients. Conclusion Our study suggests that EVT is cost-effective for treatment of acute M2 branch occlusions. Faster and improved reperfusion techniques would increase the relative cost-effectiveness of EVT even further in these patients. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of death and disability in the United States. Most strokes are ischemic, resulting in both cognitive and motor impairments. Animal models of ischemic stroke such as the distal middle cerebral artery occlusion (dMCAO) and photothrombotic stroke (PTS) procedures have become invaluable tools, with their own advantages and disadvantages. The dMCAO model is clinically relevant as it occludes the artery most affected in humans, but yields variability in the infarct location as well as the behavioral and cognitive phenotypes disrupted. The PTS model has the advantage of allowing for targeted location of infarct, but is less clinically relevant. The present study evaluates phenotype disruption over time in mice subjected to either dMCAO, PTS, or a sham surgery. Post-surgery, animals were tested over 28 days on standard motor tasks (grid walk, cylinder, tapered beam, and rotating beam), as well as a novel odor-based operant task; the 5:1 Odor Discrimination Task (ODT). Results demonstrate a significantly greater disturbance of motor control with PTS as compared with Sham and dMCAO. Disruption of the PTS group was detected up to 28 days post-stroke on the grid walk, and up to 7 days on the rotating and tapered beam tasks. PTS also led to significant short-term disruption of ODT performance (1-day post-surgery), exclusively in males, which appeared to be driven by motoric disruption of the lick response. Together, this data provides critical insights into the selection and optimization of animal models for ischemic stroke research. Notably, the PTS procedure was best suited for producing disruptions of motor behavior that can be detected with common behavioral assays and are relatively enduring, as is observed in human stroke. [ABSTRACT FROM AUTHOR]

Purpose: Recently developed machine-learning algorithms have demonstrated strong performance in the detection of intracranial hemorrhage (ICH) and large vessel occlusion (LVO). However, their generalizability is often limited by geographic bias of studies. The aim of this study was to validate a commercially available deep learning-based tool in the detection of both ICH and LVO across multiple hospital sites and vendors throughout the U.S. Materials and Methods: This was a retrospective and multicenter study using anonymized data from two institutions. Eight hundred fourteen non-contrast CT cases and 378 CT angiography cases were analyzed to evaluate ICH and LVO, respectively. The tool's ability to detect and quantify ICH, LVO, and their various subtypes was assessed among multiple CT vendors and hospitals across the United States. Ground truth was based off imaging interpretations from two board-certified neuroradiologists. Results: There were 255 positive and 559 negative ICH cases. Accuracy was 95.6%, sensitivity was 91.4%, and specificity was 97.5% for the ICH tool. ICH was further stratified into the following subtypes: intraparenchymal, intraventricular, epidural/subdural, and subarachnoid with true positive rates of 92.9, 100, 94.3, and 89.9%, respectively. ICH true positive rates by volume [small (<5 mL), medium (5–25 mL), and large (>25 mL)] were 71.8, 100, and 100%, respectively. There were 156 positive and 222 negative LVO cases. The LVO tool demonstrated an accuracy of 98.1%, sensitivity of 98.1%, and specificity of 98.2%. A subset of 55 randomly selected cases were also assessed for LVO detection at various sites, including the distal internal carotid artery, middle cerebral artery M1 segment, proximal middle cerebral artery M2 segment, and distal middle cerebral artery M2 segment with an accuracy of 97.0%, sensitivity of 94.3%, and specificity of 97.4%. Conclusion: Deep learning tools can be effective in the detection of both ICH and LVO across a wide variety of hospital systems. While some limitations were identified, specifically in the detection of small ICH and distal M2 occlusion, this study highlights a deep learning tool that can assist radiologists in the detection of emergent findings in a variety of practice settings. [ABSTRACT FROM AUTHOR]

Stroke remains a leading cause of death and disability in the United States. No current treatments exist to promote cognitive recovery in survivors of stroke. A previous study from our laboratory determined that an acute bout of forced treadmill exercise was able to promote cognitive recovery in 3 month old male rats after middle cerebral artery occlusion (MCAo). In this study, we tested the hypothesis that 6 days of intense acute bout of forced treadmill exercise (physical exercise – PE) promotes cognitive recovery in 11–14 month old male rats. We determined that PE was able to ameliorate cognitive deficits as determined by contextual fear conditioning. Additionally, we also tested the hypothesis that PE promotes cognitive recovery in 11–13 month old reproductive senescent female rats. In contrast to males, the same intensity of exercise that decrease cognitive deficits in males was not able to promote cognitive recovery in female rats. Additionally, we determined that exercise did not lessen infarct volume in both male and female rats. There are many factors that contribute to higher stroke mortality and morbidities in women and thus, future studies will investigate the effects of PE in aged female rats to identify sex differences. [ABSTRACT FROM AUTHOR]

The PHASES score was developed to determine the risk of rupture of un-ruptured intracranial aneurysms (UIAs). The purposes of the current study were to apply this score on patients with actually ruptured intracranial aneurysms and to analyze the hypothetically prediction of the risk in this particularly patient group. We extracted the data of 100 recently treated patients (23 male, 77 female, mean age 56.4 years, range 17–93 years) with ruptured saccular intracranial aneurysms from our prospectively maintained neurovascular database according to the parameters used in the PHASES score (population, hypertension, age, earlier SAH, size and site of the aneurysm). Descriptive statistical analysis was performed using SPSS for Windows version 18.0 (SPSS Inc., Chicago, Illinois, USA). Ninety-nine percent of the patients were European and 1% Japanese in our series. Pre-existing arterial hypertension was found in 59%. Fifteen percent of the patients were > 75 years. Earlier SAH was found in 1%. The site of the aneurysms were the internal carotid artery (ICA) in 10%, the middle cerebral artery (MCA) in 14%, and arteries of the anterior and posterior circulation (PC) including the posterior communicating artery (PCOM) in 76%. Sixty-six percent of the aneurysms were smaller than 7 mm, 18% ranged between 7 and 9.9 mm, 14% were between 10 and 19.9 mm, and 2% were larger than 20 mm. European population, aneurysm size < 7 mm, and age < 75 years scored with 0 point in the PHASES study occurred most frequently in our series. The distribution of the aneurysm site to the anterior and posterior circulation scored with 4 points occurred most frequently. Considering the 5-year risk of rupture, 70% of our patient collective would have an estimated risk of < 2%. Interestingly, 70% of the patients with aneurysmal SAH had a low risk profile and would have a low risk of rupture according to the PHASES score in our series. This observation underlines the discrepancy of the estimated low risk of rupture for UIAs in young and healthy patients and the obvious fact the majority of the SAH patients are actually young with low risk factors. Parameters beyond the features of the PHASES score are needed to determine the risk of rupture of intracranial aneurysms. [ABSTRACT FROM AUTHOR]

Abstract Stroke and cerebrovascular disease are now the fifth most common cause of death behind other diseases such as heart, cancer and respiratory disease and accounts for approximately 40–50 fatalities per 100,000 people each year in the United States. Currently the only therapy for acute stroke, is intravenous administration of tissue plasminogen activator which was approved in 1996 by the FDA. Surprisingly no new treatments have come on the market since, although endovascular mechanical thrombectomy is showing promising results in trials. Recently focus has shifted towards a preventative therapy rather than trying to reverse or limit the amount of damage occurring following stroke onset. During one of the components of ischemia, hypoxia, a number of physiological changes occur within neurons which include the stabilization of hypoxia-inducible factors. The activity of these proteins is regulated by O 2 , Fe2+, 2-OG and ascorbate-dependant hydroxylases which contain prolyl-4-hydroxylase domains (PHDs). PHD inhibitors are capable of pharmacologically activating the body's own endogenous adaptive response to low levels of oxygen and have therefore become an attractive therapeutic target for treating ischemia. They have been widely used in the periphery and have been shown to have a preconditioning and protective effect against a later and more severe ischemic insult. Currently there are a number of these agents in phase 1, 2 and 3 clinical trials for the treatment of anemia. In this review we assess the neuroprotective effects of PHD inhibitors, including dimethyloxalylglycine and deferoxamine and suggest that not all of their effects in the CNS are HIF-dependent. Unravelling new roles and a better understanding of the function of PHD inhibitors in the CNS may be of great benefit especially when investigating their use in the treatment of stroke and other ischemic diseases. Highlights • Stroke and cerebrovascular disease ranks as the fifth most common cause of death in the US. • PHD inhibitors can pharmacologically activate the body's own endogenous adaptive response to low levels of oxygen. • PHD inhibitors can precondition and protect against a later ischemic insult. • PHD inhibitors have a novel role in post-conditioning in the brain. • PHD inhibitors modulate synaptic transmission and plasticity in the CNS. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke has no approved treatments to enhance recovery. ALD-401 is an enriched population of aldehyde dehydrogenase-bright stem cells, capable of reducing neurological deficits in animal models. The primary objective of this trial was to determine the safety of internal carotid artery, intra-arterially delivered autologous bone marrow-derived ALD-401 in patients with disabling middle cerebral artery stroke in comparison with sham harvest with sham infusion. Secondary objectives were to determine feasibility and efficacy.Methods: This was a prospective phase 2, industry-funded, randomized, sham-controlled, parallel-group, multicenter study with blinded assessments. One hundred subjects were planned, aged 30 to 83 years, with confirmed first-time middle cerebral artery ischemic stroke with modified Rankin scale ≥3. Study patients were randomly assigned 3:2 to bone marrow harvest at 11 to 17 days after stroke followed 2 days later by intracarotid infusion of ALD-401 versus sham harvest and then sham infusion in the same timeframe. The primary study outcome was safety based on the incidence of a 4-point National Institutes of Health Stroke Scale worsening and the proportion of serious adverse events. Efficacy was based on modified Rankin scale change at 90 days. Other secondary outcomes were the proportions of patients experiencing adverse events, disability by Barthel Index, quality of life using EQ-5D, rehabilitation utilization, disability at 1 year, and MRI evidence of complications.Results: There were no infusional or allergic reactions and no difference in treatment emergent adverse events. Four patients had small areas of asymptomatic restricted diffusion on MRI in the treatment group. There was no significant difference between the ALD-401 and placebo groups on the modified Rankin scale for the intent-to-treat population at day 90 (mean difference, 0.3; 95% CI, -0.3 to 0.8; P=0.330). There were no significant differences between the groups on any of the secondary efficacy measures.Conclusions: Intracarotid infusion of ALD-401 does not lead to clinical adverse events in patients with subacute ischemic stroke, although there was a higher incidence of small lesions on MRI in the treatment group. There was no difference in the primary efficacy end point between the groups. The study provides a framework for the design and conduct of future intra-arterial cell therapy trials in stroke.Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01273337. [ABSTRACT FROM AUTHOR]

Background Recent surveys have failed to examine cerebrovascular aneurysm treatment practices among US physicians. Objective To survey physicians who are actively involved in the care of patients with cerebrovascular aneurysms to determine current aneurysm treatment preferences. Methods A 25-question SurveyMonkey online survey was designed and distributed electronically to members of the Society of NeuroInterventional Surgery, Society of Vascular and Interventional Neurology, and the American Association of Neurological Surgeons/Congress of Neurological Surgeons Combined Cerebrovascular Section. Results 211 physicians completed the survey. Most respondents recommend endovascular treatment as the first-line management strategy for most ruptured (78%) and unruptured (71%) aneurysms. Thirty-eight per cent of respondents indicate that they routinely treat all patients with subarachnoid hemorrhage regardless of grade. Most physicians use the International Study of Unruptured Intracranial Aneurysms data for counseling patients on natural history risk (80%); a small minority (11%) always or usually recommend treatment of anterior circulation aneurysms of <5 mm. Two-thirds of respondents continue to recommend clipping for most middle cerebral artery aneurysms, while most (51%) recommend flow diversion for wide-necked internal carotid artery aneurysms. Follow-up imaging schedules are highly variable. Neurosurgeons at academic institutions and those practicing longer were more likely to recommend clipping surgery for aneurysms ( p<0.05). Conclusions This survey demonstrates considerable variability in patient selection for intracranial aneurysm treatment, preferred treatment strategies, and follow-up imaging schedules among US physicians. [ABSTRACT FROM AUTHOR]

Introduction The Woven EndoBridge (WEB) represents a novel intrasaccular therapeutic option for the treatment of intracranial wide-necked bifurcation aneurysms (WNBAs). The WEB-IT Study is a pivotal Investigational Device Exemption (IDE) study to determine the safety and effectiveness of the WEB device for the treatment of WNBAs located in the anterior and posterior intracranial circulations. We present the patient demographics, procedural characteristics, and 30-day adverse event data for the US WEB-IT study. Methods WEB-IT is a prospective multicenter single-arm interventional study conducted at 25 US and 6 international centers. The study enrolled 150 adults with WNBAs of the anterior and posterior intracranial circulations. All patients were intended to receive a WEB device delivered via standard endovascular neurosurgical embolization techniques. The study was conducted under Good Clinical Practices and included independent adjudication effectiveness outcomes and all adverse events. Results One hundred and fifty patients enrolled at 27 investigational sites underwent attempted treatment with the WEB. Mean age was 59 years (range 29-79) and 110 (73.3%) of the patients were female. Treated aneurysms were located at the basilar apex (n=59, 39.3%), middle cerebral artery bifurcation (n=45, 30%), anterior communicating artery (n=40, 26.7%), and internal carotid artery terminus (n=6, 4%). Average aneurysm size was 6.4 mm (range 3.6-11.4) with a mean neck size of 4.8 mm (range 2.0-8.2, mean dome to neck ratio 1.34). Nine patients presented with ruptured aneurysms. Of the enrolled patients, 98.7% were treated successfully with WEB devices. Mean±SD fluoroscopy time was 30.2±15.7 min. One primary safety event (PSE) (0.7%)--a delayed parenchymal hemorrhage 22 days after treatment--occurred between the index procedure and 30-day follow-up. In addition to the single PSE, there were seven (4.7%) minor ischemic strokes (5 resolved without sequelae and 2 had a modified Rankin Scale score of 1 at 30 days), five (2.7%) transient ischemic attacks, and two (1.3%) minor subarachnoid hemorrhages, which did not meet the prospectively established criteria for PSEs. Conclusions The WEB device can be used to treat WNBAs with a high level of procedural safety and a high degree of technical success. Trial registration number NCT02191618; Pre-results. [ABSTRACT FROM AUTHOR]

Abstract: Global geographic disparities in stroke mortality rates are substantial. In the US alone, higher stroke mortality rates are reported in the Southeast part particularly along the coastline while lower rates have been observed in the Mountain region. The phenomenon has been called the “stroke belt”. Although many theories have attempted to explain such nonrandom distribution of stroke mortality rates, no conclusive explanations have been drawn so far. I hypothesize that this nonrandom stroke distribution is related to regional differences in individual levels of erythropoietin (EPO), a hormone, which production depends on the tissue hypoxia due to variation in altitude. If successful, future studies based on this hypothesis may open up new avenues for treatment of such an important health issue as stroke. More importantly, future studies based on this theory may shed the lights on the mechanism of stroke as well as other diseases which have nonrandom geographic distribution not only in the US but also internationally. [Copyright &y& Elsevier]

BACKGROUND AND PURPOSE Collaterals may compensate for reduced blood flow in acute ischemic stroke, yet endurance and quality of collateral perfusion may vary. Collateral sustenance of penumbra may falter after initial recruitment, resulting in progressive ischemia and clinical deficits. Delayed collateral failure may extend the time window for revascularization, even after failed intravenous thrombolysis. CASE DESCRIPTION A 76-year-old woman returned to normal from National Institutes of Health Stroke Scale (NIHSS) score of 18 following intravenous thrombolysis, despite persistent occlusion of the left middle cerebral artery. Subsequent deterioration was successfully reversed with mechanical thrombectomy almost 14 hours after symptom onset. CONCLUSIONS Early clinical improvement or deterioration may reflect collateral perfusion, not necessarily recanalization or reocclusion. The definition of collateral failure must incorporate the expected role and endurance of collaterals. Further investigation of collateral pathophysiology may reveal predictive clinical or imaging features and disclose collateral therapeutic approaches to augment revascularization. J Neuroimaging 2010;20:78-82. [ABSTRACT FROM AUTHOR]

In the United States, routine middle cerebral artery peak systolic velocity (MCA-PSV) Doppler screening for the detection of antenatal twin anemia-polycythemia sequence (TAPS) is not recommended. The current and only national clinical guideline from the highly-influential Society for Maternal-Fetal Medicine states that, "There is no evidence that monitoring for TAPS with MCA PSV Doppler at any time, including > 26 weeks, improves outcomes, so that this additional screening cannot be recommended at this time." We argue this recommendation has disproportionate influence on patients and the care they are offered and receive. We use current evidence to highlight and dispel pervasive myths surrounding antenatal TAPS and the value of routine MCA-PSV screening. An ethical framework that illustrates the importance of giving patients the opportunity for routine screening is presented. Findings demonstrate that: (1) both spontaneous and post-laser TAPS is a serious, potentially life-threatening complication, (2) treatment for TAPS is effective and includes expectant management, intrauterine transfusion (IUT), or surgery, (3) and routine MCA-PSV, which has satisfactory diagnostic accuracy, is currently the only way to provide early detection of TAPS. We conclude that routine TAPS screening is a medically proven valuable resource that should be offered to patients in need and to the clinicians who are trying to act toward their benefit. [ABSTRACT FROM AUTHOR]

Background: Functions of astrocytes in the rehabilitation after ischemic stroke, especially their impacts on inflammatory processes, remain controversial. This study uncovered two phenotypes of astrocytes, of which one was helpful, and the other harmful to anoxic neurons after brain ischemia.Methods: We tested the levels of inflammatory factors including TNF-a, IL-6, IL-10, iNOS, IL-1beta, and CXCL10 in primary astrocytes at 0 h, 6 h, 12 h, 24 h, and 48 h after OGD, grouped the hypoxia astrocytes into iNOS-positive (iNOS(+)) and iNOS-negative (iNOS(-)) by magnetic bead sorting, and then co-cultured the two groups of cells with OGD-treated neurons for 24 h. We further verified the polarization of astrocytes in vivo by detecting the co-localization of iNOS, GFAP, and Iba-1 on MCAO brain sections. Lentivirus overexpressing LCN2 and LCN2 knockout mice (#024630. JAX, USA) were used to explore the role of LCN2 in the functional polarization of astrocytes. 7.0-T MRI scanning and the modified Neurological Severity Score (mNSS) were used to evaluate the neurological outcomes of the mice.Results: After oxygen-glucose deprivation (OGD), iNOS mRNA expression increased to the peak at 6 h in primary astrocytes, but keep baseline expression in LCN2-knockout astrocytes. In mice with transient middle cerebral artery occlusion (tMCAO), LCN2 was proved necessary for astrocyte classical activation. In LCN2 knockout mice with MCAO, no classically activated astrocytes were detected, and smaller infarct volumes and better neurological functions were observed.Conclusions: The results indicated a novel pattern of astrocyte activation after ischemic stroke and lipocalin-2 (LCN2) plays a key role in polarizing and activating astrocytes. [ABSTRACT FROM AUTHOR]

Presents news briefs related to health care in the United States as of March 2001. Reason for the increased use of emergency departments; Result of a trial of a stenting system to treat blockages in cerebral arteries; Effect of the elevated levels of troponin T and C-reactive proteins; Survival rate for patients undergoing heart transplant.

Background and Purpose: Previous studies have demonstrated limited benefit with endovascular procedures such as stent placement in octogenarians. We evaluated the safety and effectiveness of intra-arterial recanalization techniques to treat ischemic stroke in patients 80 years or older presenting within 6 hours of symptom onset., Materials and Methods: We pooled the data from 4 prospective studies by evaluating intra-arterial recanalization techniques for treatment of ischemic stroke. Clinical and radiologic evaluations were performed before treatment and at 24 hours, 7 to 10 days, and 1 to 3 months after treatment. We performed multivariate analyses to evaluate the effect of ages 80 years and older on angiographic recanalization, favorable outcome (modified Rankin scale of 0-2), and mortality rate at 1 to 3 months., Results: A total of 101 patients were treated in the 4 protocols. Of these, 24 were 80 years or older. There was no significant difference between the 2 age groups in sex, initial stroke severity, time to treatment, site of vascular occlusion, and rate of symptomatic and asymptomatic intracranial hemorrhage (ICH). In logistic regression analysis, age 80 years or older was associated with a lower likelihood of a favorable outcome (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.13-1.2; P = .11) and recanalization (OR, 0.36; 95% CI, 0.12-1.1; P = .07) and with higher mortality rate (OR, 3.17; 95% CI, 1.05-9.55; P = .04) after adjusting for study protocol. After adjusting for recanalization in addition to study protocol, the older age group still had a lower likelihood of favorable outcomes (OR, 0.34; 95% CI, 0.1-1.1; P = .07) and higher mortality rates (OR, 3.62; 95% CI, 1.15-11.36; P = .027)., Conclusions: Our study demonstrates that patients 80 years and older are at higher risk for poor outcome at 1 to 3 months following intra-arterial recanalization techniques. This relationship is independent of recanalization rate and symptomatic ICH supporting the role of other mechanisms.

Background and Purpose: Stroke scales are intended to measure stroke severity for the purpose of clinical trials. Scores have been used to determine trial entry, to compare patient groups within or between trials, or as a secondary end point. The use of scores as an end point in meta-analysis has not been validated, but such analyses have nevertheless been performed when equivocal results have been obtained using the main outcome measure. The different scale designs suggest that conversion of scores may not be possible. We sought to determine whether scores on different scales could be interconverted., Methods: A single observer scored 433 consecutive admissions to an acute stroke unit on the Canadian Neurological Scale, the middle cerebral artery Neurological Score (or Orgogozo scale), and the National Institutes of Health stroke scale. Data were separated into training and test sets, and linear regression was used to model conversion between scales. Prediction errors were calculated. Strokes were subdivided according to the Oxfordshire Community Stroke Project classification, and coefficients of determination were calculated for different subtypes., Results: Conversion between Canadian and middle cerebral artery Neurological scales was satisfactory (R2 = 94.7%), and prediction errors were acceptable (absolute prediction error, 5.0 +/- 5). Conversion from the National Institutes of Health scale was worse (R2 = 87.5% to Canadian and 89.0% to Neurological Score), and prediction errors were significantly greater (Neurological Score error, 8.7 +/- 7; Canadian Neurological Scale error, 8.5 +/- 7.3; P < .005 for both). Coefficients of determination for interconversion were significantly worse for dysphasic patients with total anterior circulation strokes than for other stroke types (P < .01). Reweighting the motor component of the National Institutes of Health scale improved coefficients of determination and reduced prediction errors, but prediction error for conversion to the Canadian scale remained significantly greater than other conversions (P = .001)., Conclusions: The Canadian Neurological Scale and the middle cerebral artery Neurological Score may reliably be converted. The National Institutes of Health scale cannot be used to predict these scores reliably, even with reweighting of the motor score. Interconversion is poorest for patients with dysphasia and total anterior circulation strokes. These results suggest that there will be more general difficulty in interconverting scales that use different test items and weighting. Meta-analysis using sequential changes in averaged scores from various stroke scales is not valid.

Background and Purpose: The National Institutes of Health (NIH) Stroke Scale has been used in clinical trials to assess neurological outcome after investigational therapy for acute stroke. We used the NIH Stroke Scale to study the degree and time course of recovery in patients with acute stroke who were treated with conventional therapy., Methods: We serially assessed 50 patients with ischemic stroke who presented within 24 hours of onset of symptoms. Patients were grouped by stroke subtype. Major neurological improvement was defined as a decrease in the stroke score by 4 points or more., Results: The mean NIH stroke score for all patients improved significantly by 7 to 10 days and at last follow-up (average, 44 days). Major neurological improvement was seen in 5 of 41 patients (12%; 95% confidence interval [CI], 2% to 22%) by 24 hours, 11 of 40 patients (28%; 95% CI, 14% to 41%) by 48 hours, and 19 of 37 patients (51%; 95% CI, 35% to 67%) by follow-up. The subgroup of patients with middle cerebral artery territory embolism showed a similar pattern of improvement; in contrast, patients with lacunar infarcts did not show significant change in scores during the study period. The score on admission did not correlate with the degree of subsequent improvement or deterioration., Conclusions: A significant percentage of patients with acute ischemic stroke treated with conventional therapy show early improvement as assessed by the NIH Stroke Scale. The degree and time course of recovery may be influenced by stroke type.