Standards of Practice in Acute Ischemic Stroke Intervention: International Recommendations

n/

Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression

Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

Endovascular treatment of posterior condylar canal dural arteriovenous fistula

Posterior condylar canal dural arteriovenous fistulas (PCC DAVFs) are rare lesions that may present with pulse-synchronous bruit. In cases with venous reflux there is a risk of haemorrhage or even dementia. Diagnosis and endovascular treatment require a profound knowledge of the vascular anatomy of the craniocervical junction and comprehensive neurovascular imaging. We describe the clinical presentation, angiographic imaging and endovascular treatment of a PCC DAVF in a female patient with pulse-synchronous bruit as the presenting symptom. The fistula drained almost exclusively into the sigmoid sinus and internal jugular vein. There was no intracranial reflux. The PCC DAVF was treated with transvenous coil occlusion of the fistulous pouch in the condylar canal. Symptoms resolved immediately after intervention and the patient recovered quickly without any neurological deficits. MR angiography confirmed occlusion of the DAVF. The dural sinus was patent with normal blood flow

Stenting of the cervical internal carotid artery in acute stroke management: The Karolinska experience

Background: Emergency stent placement in the extracranial internal carotid artery in combination with anterior circulation thrombectomy is a routine procedure. Yet, precise indications and clinical safety in this setting remains controversial. Present data for mechanical thrombectomy include few studies with acute stenting of tandem occlusions. We evaluated the feasibility, safety and clinical outcome of this endovascular treatment in a retrospective analysis of all consecutive cases at a comprehensive stroke centre. Methods: This was a retrospective analysis of all consecutive patients with acute extracranial carotid artery occlusion including acute dissection or high-grade stenosis and concomitant intracranial large-vessel occlusion treated with emergency carotid stenting and intracranial mechanical thrombectomy between November 2007 and May 2015. Results: A total of 63 patients with a median age of 67 years (range 33-84 years) were treated. Of these, 33 (52%) patients had concomitant intravenous thrombolysis with recombinant tissue-type plasminogen activator initially. Median admission National Institutes of Health Stroke Scale was 14 (range 1-29). Median time from stroke onset to recanalization was 408 minutes (range 165-1846 minutes). Procedure time was significantly shorter after intravenous thrombolysis (110 minutes [range 15-202 minutes] vs. 130 minutes [range 60-280 minutes]; p = 0.02). Three (5%) patients experienced post-procedural symptomatic intracerebral haemorrhage. In 55/63 (87%) patients, a score of >= 2b on the Thrombolysis in Cerebral Infarction scale could be achieved. Eight (13%) patients died, five (8%) during the acute phase. A total of 29/63 (46%) patients showed a favourable outcome (modified Rankin Scale score of 0-2) after three months. Conclusions: Our single-centre retrospective analysis of emergency stent placement in the extracranial internal carotid artery in combination with anterior circulation thrombectomy demonstrated high technical success, reasonable clinical outcomes and acceptable rates of symptomatic intracranial haemorrhage in carefully chosen patients which are triaged interdisciplinary based on clinical and computed tomography imaging criteria. This warrants further study in a randomised prospective trial

Spinal cord arteriovenous shunts of the ventral (anterior) sulcus: anatomical, clinical, and therapeutic considerations

Introduction: Ventral sulcus spinal cord arteriovenous shunts (SCAVS) are rare vascular lesions that are located outside the spinal cord, are exclusively vascularized by the anterior spinal axis, and drain exclusively through the anterior spinal vein. We report the anatomical, clinical, and neuro-radiological features of SCAVS managed by our team. Methods: We conducted a retrospective study of patients with SCAVSs evaluated by the senior author of this report (GR) between 1981 and 2014. Data were collected by reviewing clinical notes and by a systematic analysis of spinal angiograms and MRI. Results: Among 358 patients, we identified 8 patients (3 women) with ventral sulcus spinal cord arteriovenous shunts. Mean age was 30.5\uc2\ua0years. Six patients presented with progressive neurological symptoms, and two with acute neurological symptoms related to hematomyelia. Three shunts were located in the cervical cord, four in the thoracic cord, and one at the conus medullaris; there were two nidus type A-V shunts (AVMs) and six fistula type A-V shunts (AVFs). Seven patients were treated by endovascular therapy with glue embolization. Embolization led to anatomical cure in 5 cases, and a significant reduction of shunt volume and flow of more than 75% in 2 cases. In none of the cases we observed permanent morbidity. Conclusions: AVS of the ventral sulcus of the spinal cord are rare. Recognition of these lesions and precise localization of the anatomical space in which they are located, may allow a better understanding of their pathophysiology and clinical manifestations and guide proper therapeutic decisions

Optical Detection of the Brachial Plexus for Peripheral Nerve Blocks An In Vivo Swine Study

Background and Objectives: Accurate identification of nerves is critical to ensure safe and effective delivery of regional anesthesia during peripheral nerve blocks. Nerve stimulation is commonly used, but it is not perfect. Even when nerve stimulation is performed in conjunction with ultrasound guidance, determining when the needle tip is at the nerve target region can be challenging. In this in vivo pilot study, we investigated whether close proximity to the brachial plexus and penetration of the axillary artery can be identified with optical reflectance spectroscopy, using a custom needle stylet with integrated optical fibers. Methods: Ultrasound-guided insertions to place the needle tip near the brachial plexus at the axillary level were performed at multiple locations in 2 swine, with the stylet positioned in the cannula of a 20-gauge stimulation needle. During each insertion, optical reflectance spectra were acquired with the needle tip in skeletal muscle, at the surface of muscle fascia, and at the nerve target region; confirmation of the final needle position was provided by nerve stimulation. In addition, an insertion to the lumen of the axillary artery was performed in a third swine. Differences in the spectra were quantified with lipid and hemoglobin parameters that provide contrast for optical absorption by the respective chromophores. Results: The transition of the needle tip from skeletal muscle to the nerve target region was associated with higher lipid parameter values (P <0.001) and lower hemoglobin parameter values (P <0.001). The transition of the needle tip from muscle fascia to the nerve target region was associated with higher lipid parameter values (P = 0.001). Intraluminal access of the axillary artery was associated with an elevated hemoglobin parameter. Conclusions: Spectroscopic information obtained with the optical needle is distinct from nerve stimulation and complementary to ultrasound imaging, and it could potentially allow for reliable identification of the injection site during peripheral nerve blocks