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Because the time spent evaluating the patient in the emergency department, which typically includes neuroimaging studies performed in scanners remote from the angiography suite, represents the main source of delays in thrombectomy initiation, the direct to angiography (DTA) model has emerged as a means to substantially reduce treatment times and is being instituted at an increasing number of thrombectomy centers across the world. The aim of this report is to introduce DTA as an emerging stroke care paradigm for patients with suspicion of LVO stroke, review results from studies evaluating its feasibility and impact on outcomes, describe current barriers to its more widespread adoption, and propose potential solutions to overcoming these barriers.

This article reviews common imaging modalities used in diagnosis and management of acute stroke. Each modality is discussed individually and clinical scenarios are presented to demonstrate how to apply these modalities in decision-making.

Advances in neuroimaging provide unprecedented accuracy in determining tissue viability as well as tissue fate in acute stroke. In addition, advances in machine learning have led to the creation of decision support tools to improve the interpretability of these studies.

Noncontrast head computed tomography (CT) remains the most commonly used initial imaging tool to evaluate stroke. Its exquisite sensitivity for hemorrhage, rapid acquisition, and widespread availability make it the ideal first study. CT angiography (CTA), the most common follow-up study after noncontrast head CT, is used primarily to identify intracranial large vessel occlusions and cervical carotid or vertebral artery disease. CTA is highly sensitive and can improve accuracy of patient selection for eny after noncontrast head CT, is used primarily to identify intracranial large vessel occlusions and cervical carotid or vertebral artery disease. CTA is highly sensitive and can improve accuracy of patient selection for endovascular therapy through delineations of ischemic core. CT perfusion is widely used in endovascular therapy trials and benefits from multiple commercially available machine-learning packages that perform automated postprocessing and interpretation. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) can provide valuable insights for outcomes prognostication as well as stroke etiology. Optical coherence tomography (OCT), positron emission tomography (PET), single-photon emission computerized tomography (SPECT) offer similar insights. In the clinical scenarios presented, we demonstrate how multimodal imaging approaches can be tailored to gain mechanistic insights for a range of cerebrovascular pathologies.Time to reperfusion is one of the strongest predictors of functional outcome in acute stroke due to a large vessel occlusion (LVO). Direct transfer to angiography suite (DTAS) protocols have shown encouraging results in reducing in-hospital delays. DTAS allows bypassing of conventional imaging in the emergency room by ruling out an intracranial hemorrhage or a large established infarct with imaging performed before transfer to the thrombectomy-capable center in the angiography suite using flat-panel CT (FP-CT). The rate of patients with stroke code primarily admitted to a comprehensive stroke center with a large ischemic established lesion is less then 10% within 6 hours from onset and remains less then 20% among patients with LVO or transferred from a primary stroke center. At the same time, stroke severity is an acceptable predictor of LVO. Therefore, ideal DTAS candidates are patients admitted in the early window with severe symptoms. The main difference between protocols adopted in different centers is the inclusion of FP-CT angiography to confirm an LVO before femoral puncture. While some centers advocate for FP-CT angiography, others favor additional time saving by directly assessing the presence of LVO with an angiogram. The latter, however, leads to unnecessary arterial punctures in patients with no LVO (3%-22% depending on selection criteria). Independently of these different imaging protocols, DTAS has been shown to be effective and safe in improving in-hospital workflow, achieving a reduction of door-to-puncture time as low as 16 minutes without safety concerns. The impact of DTAS on long-term functional outcomes varies between published studies, and randomized controlled trials are warranted to examine the benefit of DTAS.

This article reviews prehospital organization in the treatment of acute stroke. Rapid access to an endovascular therapy (EVT) capable center and prehospital assessment of large vessel occlusion (LVO) are 2 important challenges in acute stroke therapy. This article emphasizes the use of transfer protocols to assure the prompt access of patients with an LVO to a comprehensive stroke center where EVT can be offered. Available prehospital clinical tools and novel technologies to identify LVO are also discussed. Moreover, different routing paradigms like first attention at a local stroke center ("drip and ship"), direct transfer of the patient to an endovascular center ("mothership"), transfer of the neurointerventional team to a local primary center ("drip and drive"), mobile stroke units, and prehospital management communication tools all aimed to improve connection and coordination between care levels are reviewed.

Local observational data and mathematical models suggest that implementing triage tools and bs would optimally lead to individualized real-time decision-making.

This article aims to provide an update on the designation of stroke centers, neurointerventionalist demand, and cost-effectiveness of stroke thrombectomy in the United States.

There are now more than 1,660 stroke centers certified by national accrediting bodies in the United States, 306 of which are designated as thrombectomy-capable or comprehensive stroke centers. Considering the amount of nationally certified centers and the number of patients with acute stroke eligible for thrombectomy, each center would be responsible for 64 to 104 thrombectomies per year. As a result, there is a growing demand placed on neurointerventionalists, who have the ability to alter the trajectory of large vessel occlusive strokes. Numbers needed to achieve functional independence after stroke thrombectomy at 90 days range from 3.2 to 7.4 patients in the early time window and 2.8 to 3.6 patients in the extended time window in appropriately selected candidates. With the low number needed to treat, in a variety of valued-basedd experience, we must continue to re-evaluate cost-effectiveness, strike a balance between sufficient case volumes to maintain clinical excellence vs the burden and burnout associated with call responsibilities, and improve access to care for all.

To provide an up-to-date review of the incidence of stroke and large vessel occlusion (LVO) around the globe, as well as the eligibility and access to IV thrombolysis (IVT) and mechanical thrombectomy (MT) worldwide.

Randomized clinical trials have established MT with or without IVT as the usual care for patients with LVO stroke for up to 24 hours from symptom onset. Eligibility for IVT has extended beyond 4.5 hours based on permissible imaging criteria. With these advances in the last 5 years, there has been a notable increase in the population of patients eligible for acute stroke interventions. However, access to acute stroke care and utilization of MT or IVT is lagging in these patients.

Stroke is the second leading cause of both disability and death worldwide, with the highest burden of the disease shared by low- and middle-income countries. In 2016, there were 13.7 million new incident strokes globally; ≈87% of these were ischemic strokes and by conservative estimation about 10%-20% of these accouadvances across the globe. Multiple global initiatives are underway to investigate interventions to improve systems of care and bridge this gap.Zika virus (ZIKV) during pregnancy infects fetal trophoblasts and causes placental damage and birth defects including microcephaly. Little is known about the anti-ZIKV cellular immune response at the maternal-fetal interface. Decidual natural killer cells (dNK), which directly contact fetal trophoblasts, are the dominant maternal immune cells in the first-trimester placenta, when ZIKV infection is most hazardous. Although dNK express all the cytolytic molecules needed to kill, they usually do not kill infected fetal cells but promote placentation. Here, we show that dNK degranulate and kill ZIKV-infected placental trophoblasts. ZIKV infection of trophoblasts causes endoplasmic reticulum (ER) stress, which makes them dNK targets by down-regulating HLA-C/G, natural killer (NK) inhibitory receptor ligands that help maintain tolerance of the semiallogeneic fetus. ER stress also activates the NK activating receptor NKp46. ZIKV infection of Ifnar1 -/- pregnant mice results in high viral titers and severe intrauterine growth restriction, which are exacerbated by depletion of NK or CD8 T cells, indicating that killer lymphocytes, on balance, protect the fetus from ZIKV by eliminating infected cells and reducing the spread of infection.Roughly 10% of the human population is left-handed, and this rate is increased in some brain-related disorders. The neuroanatomical correlates of hand preference have remained equivocal. We resampled structural brain image data from 28,802 right-handers and 3,062 left-handers (UK Biobank population dataset) to a symmetrical surface template, and mapped asymmetries for each of 8,681 vertices across the cerebral cortex in each individual. Left-handers compared to right-handers showed average differences of surface area asymmetry within the fusiform cortex, the anterior insula, the anterior middle cingulate cortex, and the precentral cortex. Meta-analyzed functional imaging data implicated these regions in executive functions and language. Polygenic disposition to left-handedness was associated with two of these regional asymmetries, and 18 loci previously linked with left-handedness by genome-wide screening showed associations with one or more of these asymmetries. Implicated genes included six encoding microtubule-related proteins TUBB, TUBA1B, TUBB3, TUBB4A, MAP2, and NME7-mutations in the latter can cause left to right reversal of the visceral organs. There were also two cortical regions where average thickness asymmetry was altered in left-handedness on the postcentral gyrus and the inferior occipital cortex, functionally annotated with hand sensorimotor and visual roles. These cortical thickness asymmetries were not heritable. Heritable surface area asymmetries of language-related regions may link the etiologies of hand preference and language, whereas nonheritable asymmetries of sensorimotor cortex may manifest as consequences of hand preference.MicroRNAs (miRNAs) have recently emerged as important regulators of ion channel expression. We show here that select miR-106b family members repress the expression of the KCNQ2 K+ channel protein by binding to the 3'-untranslated region of KCNQ2 messenger RNA. During the first few weeks after birth, the expression of miR-106b family members rapidly decreases, whereas KCNQ2 protein level inversely increases. Overexpression of miR-106b mimics resulted in a reduction in KCNQ2 protein levels. Selleckchem Vistusertib Conversely, KCNQ2 levels were up-regulated in neurons transfected with antisense miRNA inhibitors. By constructing more specific and stable forms of miR-106b controlling systems, we further confirmed that overexpression of precursor-miR-106b-5p led to a decrease in KCNQ current density and an increase in firing frequency of hippocampal neurons, while tough decoy miR-106b-5p dramatically increased current density and decreased neuronal excitability. These results unmask a regulatory mechanism of KCNQ2 channel expression in early postnatal development and hint at a role for miR-106b up-regulation in the pathophysiology of epilepsy.

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