关键词： anaesthesia   blood pressure   conscious sedation   reperfusion   stroke  

摘要： Background: Observational studies have suggested that low blood pressure and blood pressure variability may partially explain adverse neurological outcome after endovascular therapy with general anaesthesia (GA) for acute ischaemic stroke. The aim of this study was to further examine whether blood pressure related parameters during endovascular therapy are associated with neurological outcome. Methods: The GOLIATH trial randomised 128 patients to either GA or conscious sedation for endovascular therapy in acute ischaemic stroke. The primary outcome was 90 day modified Rankin Score. The haemodynamic protocol aimed at keeping the systolic blood pressure >140 mm Hg and mean blood pressure >70 mm Hg during the procedure. Blood pressure related parameters of interest included 20% reduction in mean blood pressure;mean blood pressure <70 mm Hg, <80 mm Hg, and <90 mm Hg, respectively;time with systolic blood pressure <140 mm Hg;procedural minimum and maximum mean and systolic blood pressure;mean blood pressure at the time of groin puncture;postreperfusion mean blood pressure;blood pressure variability;and use of vasopressors. Sensitivity analyses were performed in the subgroup of reperfused patients. Results: Procedural average mean and systolic blood pressures were higher in the conscious sedation group (P<0.001). The number of patients with mean blood pressure <70-90 mm Hg and systolic blood pressure <140 mm Hg, blood pressure variability, and use of vasopressors were all higher in the GA group (P<0.001). There was no statistically significant association between any of the examined blood pressure related parameters and the modified Rankin Score in the overall patient population, and in the subgroup of patients with full reperfusion. Conclusion: We found no statistically significant association between blood pressure related parameters during endovascular therapy and neurological outcome.

摘要： A key site of translation control is the phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2 alpha), which reduces the rate of GDP to GTP exchange by eIF2B, leading to altered translation. The extent of eIF2 alpha phosphorylation within neurons can alter synaptic plasticity. Phosphorylation of eIF2 alpha is triggered by four stress- responsive kinases, and as such eIF2 alpha is often phosphorylated during neurological perturbations or disease. Moreover, in some cases decreasing eIF2 alpha phosphorylation mitigates neurodegeneration, suggesting that this could be a therapeutic target. Mutations in the gamma subunit of eIF2, the guanine exchange factor eIF2B, an eIF2 alpha phosphatase, or in two eIF2 alpha kinases can cause disease in humans, demonstrating the importance of proper regulation of eIF2 alpha phosphorylation for health.

关键词： Exome sequencing   Dystonia   Ataxia   MRI   Recessive   Consanguineous  

摘要： Background: Neurological disorders comprise a large group of clinically and genetically heterogeneous disorders, many of which have a genetic cause. In addition to a detailed neurological examination, exome sequencing is being increasingly used as a complementary diagnostic tool to identify the underlying genetic cause in patients with unclear, supposedly genetically determined disorders. Objective: To identify the genetic cause of a complex movement disorder in five consanguineous Pakistani families. Methods: We included five consanguineous Pakistani families with complex recessively inherited movement disorders. Clinical investigation including videotaping was carried out in a total of 59 family members (4-21 per family) and MRI in six patients. Exome sequencing was performed in 4-5 family members per pedigree to explore the underlying genetic cause. Results: Patients presented a wide spectrum of neurological symptoms including ataxia and/or dystonia. We identified three novel homozygous, segregating variants in ATCAY (***200Profs*20), MCOLNI (p.1le184Thr), and SACS (***3040Lysfs*4) in three of the families. Thus, we were able to identify the likely cause of the disease in a considerable number of families (60%) with the relatively simple and nowadays widely available method of exome sequencing. Of note, close collaboration of neurologists and geneticists was instrumental for proper data interpretation. Conclusions: We expand the phenotypic, genotypic, and ethnical spectrum of mutations in these genes. Our findings alert neurologists that rare genetic causes should be considered in complex phenotypes regardless of ethnicity. (C) 2018 Elsevier Ltd. All rights reserved.

关键词： Atropa belladonna   Deadly nightshade   Neurotoxicity   Neurological disorders   Atropine   Scopolamine   Hyoscyamine   Teething drugs  

摘要： Atropa belladonna, commonly known as belladonna or deadly nightshade, ranks among one of the most poisonous plants in Europe and other parts of the world. The plant contains tropane alkaloids including atropine, scopolamine, and hyoscyamine, which are used as anticholinergics in Food and Drug Administration (FDA) approved drugs and homeopathic remedies. These alkaloids can be very toxic at high dose. The FDA has recently reported that Hyland's baby teething tablets contain inconsistent amounts of Atropa belladonna that may have adverse effects on the nervous system and cause death in children, thus recalled the product in 2017. A greater understanding of the neurotoxicity of Atropa belladonna and its modification of genetic polymorphisms in the nervous system is critical in order to develop better treatment strategies, therapies, regulations, education of at risk populations, and a more cohesive paradigm for future research. This review offers an integrated view of the homeopathy and neurotoxicity of Atropa belladonna in children, adults, and animal models as well as its implications to neurological disorders. Particular attention is dedicated to the pharmaco/toxicodynamics, pharmaco/toxicokinetics, pathophysiology, epidemiological cases, and animal studies associated with the effects of Atropa belladonna on the nervous system. Additionally, we discuss the influence of active tropane alkaloids in Atropa belladonna and other similar plants on FDA-approved therapeutic drugs for treatment of neurological disorders.

关键词： chimeric antigen receptor-T therapy   cytokine release syndrome   central nervous system   coagulation  

摘要： The article reports on the case of a ten-year-old boy who developed serious cytokine release syndrome (CRS), a complication of chimeric antigen receptor (CAR)-modified T cell (CAR-T) therapy in a phase-one clinical trial. The patient, who was diagnosed with B-cell acute lymphoblastic leukaemia eight years ago, suffered from central nervous system (CNS) symptoms and coagulopathy. The importance of timely diagnosis and the right approach to the management of CNS problems is emphasized.

关键词： autoimmunity   common variable immunodeficiency disease   sarcoidosis   systemic lupus erythematous   Sjogren's syndrome   inflammatory disorder  

摘要： When patients present with neurological syndromes, such as encephalopathy/encephalitis, meningitis, and/or myelopathy/myelitis, the differential diagnosis is often broad, including infectious, inflammatory, autoimmune, vascular, and neoplastic etiologies. Just with inflammatory and autoimmune etiologies alone, there are numerous causative diseases. A comprehensive history and physical examination investigating for extraneurologic manifestations of immune-mediated disease is often necessary. Moreover, evaluating for an underlying infection and/or immunodeficiency becomes a critical aspect to the workup. This article will focus on the association of viral infections and dysregulation of the immune system as triggers of autoimmunity, in addition to various systemic inflammatory diseases that can cause neurological disease either with or without an established rheumatological disorder.

关键词： Spinal metastases   Functional outcome   Neurosurgery   Spinal surgery   Laminectomy   Tumor debulking  

摘要： Objective: Space-occupying spinal metastases (SM), commonly diagnosed because of acute neurological deterioration, consequently lead to immediate decompression with tumor removal or debulking. In this study, we analyzed a series of patients with surgically treated spinal metastases and explicitly sought to determine individual predictors of functional outcome. Patients and methods: 94 patients (26 women, 68 men;mean age 64.0 years) with spinal metastases, who had been surgically treated at our department, were included retrospectively. We reviewed the pre- and postoperative charts, surgical reports, radiographic data for demographics, duration of symptoms, histopathology, stage of systemic disease, co-morbidities, radiographic extension, surgical strategy, neurological performance (Frankel Grade Classification), and the Karnofsky Performance Index (KPI). Results: Emergency surgery within <24 h after discharge had been conducted in 33% of patients. Prostate carcinoma (29.5%) and breast carcinoma (11.6%) were the most common histopathologies. Median KPI was 60% at admission that had significantly improved at discharge (KPI 70%;p = 0.01). The rate of complications without revision was 4.3%, the revision rate 4.2%. From admission to discharge, pain had been significantly reduced (p = 0.019) and motor deficits significantly improved (p = 0.003). KPI had been significantly improved during in-hospital treatment (median 60 vs 70, p = 0.010). In the multivariable analysis, predictors of poor outcome (KPI < 70) were male sex, multiple metastases, and pre-existing bowel and bladder dysfunction. Median follow up was 2 months. Discussion: In our series, surgery for spinal metastases (laminectomy, tumor removal, and mass reduction) significantly reduced pain as well as sensory and motor deficits. We identified male sex, multiple metastases, and pre-existing bowel and bladder dysfunction as predictors of negative outcome. (C) 2018 Elsevier Ltd. All rights reserved.

关键词： Apgar score   Cerebral palsy   Epilepsy   Intellectual disability   Sensorineural defects  

摘要： Aim: This study evaluated the associations between low Apgar scores at one and five minutes and long-term neurological impairments. Methods: This study used population-based data on 399,815 singletons born in Finland in 2004-2010 and multivariable logistic regression to examine any associations between low (0-3) and intermediate (4-6) Apgar scores and cerebral palsy, epilepsy, intellectual disability and sensorineural defects by the age of four years. Results: The odd ratios (OR) and 95% confidence intervals (95% CI) showed that low Apgar scores were associated with cerebral palsy at one and five minutes (ORs 2.08, 95% CI 1.32-3.26 and 5.19, 95% CI 3.06-8.80), epilepsy (ORs 1.62, 95% CI 1.13-2.33 and 4.79, 95% CI 3.03-7.56), and intellectual disability (ORs 2.46, 95% CI 1.45-4.16 and 6.21, 95% CI 3.33-11.58). Only a low five-minute Apgar score was associated with sensorineural defects (OR 3.13, 95% CI 1.95-5.02). Neurological impairment risks were increased by low Apgar scores at both one and five minutes (OR 11.1, 95% CI 8.6-14.5), but 90.3% of children with persistent low Apgar scores had no impairment. Conclusion: Low one-minute and five-minute Apgar scores were associated with long-term neurological morbidity, especially when both scores were low.

关键词： Reaching performance scale   Upper limb   Kinect   Kinect V2   Biomechanical evaluation   Neurological patients   Kinematics   Motion tracking   Motor control  

摘要： Automated procedures for neurological patients' motor evaluation may take advantage of the coupling between clinical scales and motion tracking devices to provide affordable, quantified and reliable assessment to be used in clinics, in surgeries and domestic environment. In this study, 20 post-stroke patients performed frontal reaching movements with their more affected limb, and a physician administered the Reaching Performance Scale (RPS) to assess motor functionality. At the same time, patients' kinematics were recorded with the Kinect V2 sensor. An automated algorithm was developed to compute the RPS based on Kinect V2 tracking data, and visual and Kinect V2 RPS scores were compared. Results showed very high statistical correlation between the automated procedure and the visual administration (Pearson Correlation Coefficient: R=0.90, p<0.001). While the number of patients is limited, the automated RPS seems to be successfully applicable to different levels of impairment, from mild to severe. (C) 2018 IPEM. Published by Elsevier Ltd. All rights reserved.