关键词： Acute ischemic stroke   blood-brain barrier   small extracellular vesicles   tPA   endothelial cells  

摘要： Treatment of patients with cerebral large vessel occlusion with thrombectomy and tissue plasminogen activator (tPA) leads to incomplete reperfusion. Using rat models of embolic and transient middle cerebral artery occlusion (eMCAO and tMCAO), we investigated the effect on stroke outcomes of small extracellular vesicles (sEVs) derived from rat cerebral endothelial cells (CEC-sEVs) in combination with tPA (CEC-sEVs/tPA) as a treatment of eMCAO and tMCAO in rat. The effect of sEVs derived from clots acquired from patients who had undergone mechanical thrombectomy on healthy human CEC permeability was also evaluated. CEC-sEVs/tPA administered 4 h after eMCAO reduced infarct volume by similar to 36%, increased recanalization of the occluded MCA, enhanced cerebral blood flow (CBF), and reduced blood-brain barrier (BBB) leakage. Treatment with CEC-sEVs given upon reperfusion after 2 h tMCAO significantly reduced infarct volume by similar to 43%, and neurological outcomes were improved in both CEC-sEVs treated models. CEC-sEVs/tPA reduced a network of microRNAs (miRs) and proteins that mediate thrombosis, coagulation, and inflammation. Patient-clot derived sEVs increased CEC permeability, which was reduced by CEC-sEVs. CEC-sEV mediated suppression of a network of pro-thrombotic, -coagulant, and -inflammatory miRs and proteins likely contribute to therapeutic effects. Thus, CEC-sEVs have a therapeutic effect on acute ischemic stroke by reducing neurovascular damage.

关键词： COVID-19   Neurology residency   Social media   Virtual events  

摘要： Objective: To determine how neurology departments and residency programs in the United States used virtual communication to adapt to the COVID-19 pandemic, we investigated the presence and use of social media pages, virtual outreach events, and virtual internship opportunities. Methods: Twitter, Instagram, and Facebook accounts were identified (or noted as nonexistent) for 159 accredited neurology departments and residency programs. Google searches and social media site specific searches were performed. For existing pages, the date of creation was determined and all posts on and after March 1st, 2020, were assessed to investigate the presence of virtual open house advertisements. Each program was also assessed for virtual sub-internship and elective opportunities on the Visiting Student Application Service (VSAS). Results: A majority of neurology residency programs (110) had a social media presence, particularly on Twitter and Instagram. Most residency program Twitter and Instagram accounts were created after March 1st, 2020, and this was not the case on Facebook. Twitter and Instagram were used most to advertise virtual opportunities. A correlation was observed between presence and number of social media accounts and program prestige. Few programs offered virtual opportunities on VSAS for the 2020-2021 year. Conclusion: Neurology residency programs adapted to the COVID-19 pandemic by creating residency social media accounts, primarily on Instagram and Twitter, and hosting virtual informational events. We recommend that neurology residency applicants create professional Instagram and Twitter accounts to network with programs and receive updates about virtual events. Similarly, going forward, we recommend continued social media use by neurology residency programs for applicant outreach.

关键词： lung cancer   non-small cell lung cancer   paraneoplastic neurological syndrome   small cell lung cancer  

摘要： Background Paraneoplastic syndrome is a distant effect caused by malignant tumors, which is related to the production of cellular immune response. The nervous system is the most common involved system of paraneoplastic syndrome. It is easy to be misdiagnosed. Lung cancer is the most common cancer relating to paraneoplastic neurological syndrome (PNS). Method This study retrospectively analyzed clinical data of patients with the combination of PNS and lung cancer between January 2005 and March 2021 at Qilu Hospital of Shandong University, China. Results A total of 111 patients were diagnosed with lung cancer complicated with PNS. A total of 95 (85.6%) cases had neurological symptoms as the first symptom. Sixty-three cases had the pathological results. A total of 43 (68.3%) of small cell lung cancer (SCLC) were diagnosed. PNS patients diagnosed with SCLC included peripheral neuropathy (15 cases, 34.9%). PNS patients diagnosed with non-small cell lung cancer (NSCLC) included peripheral neuropathy (6 cases, 30%) and limbic encephalitis (6 cases, 30%). Anti-Hu is popular in patients with SCLC (12 cases, 42.9%) and NSCLC (6 cases, 40%). Conclusions Most patients with PNS had neurological symptoms as the first symptom. It was more common in males. It had a higher incidence in SCLC. Peripheral neuropathy was the most common PNS associated with SCLC, followed by Lambert-Eaton syndrome. Peripheral neuropathy and limbic encephalitis were the most common PNS associated with NSCLC. Anti-Hu is the most common antibodies both in SCLC and NSCLC. Tumor markers do not have significant difference between different pathological types.

关键词： Medical education   Neurology  

摘要： Aim We aim to determine the efficacy of an intensive week of large group tutorials in the teaching of neurology to medical students. We also look to compare teaching methods within our centre. Methods Students were asked to complete a questionnaire before and after large group tutorials ranking their confidence in neurology. Students from two consecutive years were studied, each using a different tutorial method. An 'intensive week' approach was then compared to a 'once a week' approach. Results Responses from pre and post the tutorial week were compared. Students reported an improvement in all domains following either method of delivering tutorials. There was no statistically significant difference between the two approaches. Conclusion Large group tutorials are an effective way of delivering neurology teaching to undergraduate medical students.

关键词： Intracerebral hemorrhage   Neurological deficit   SUMO1 knockout   Cardiac dysfunction   Inflammation  

摘要： Small ubiquitin-like modifier 1 (SUMO1) reduces cardiac hypertrophy and induces neuroprotective effects. Previous studies have found that intracerebral hemorrhage (ICH) provokes cardiac deficit in the absence of primary cardiac diseases in mice. In this study, we tested the hypothesis that SUMO1 deficiency leads to worse brain and heart dysfunction after ICH and SUMO1 plays a key role in regulating brain-heart interaction after ICH in aged mice. Aged (18-20 months) female SUMO1 null (SUMO1(-/-)) mice and wild-type (WT) C57BL/6 J mice were randomly divided into four groups (n = 8/group): (1) WT-sham group, (2) SUMO1(-/-)-sham group, (3) WT-ICH group, and (4) SUMO1(-/-)-ICH group. Cardiac function was measured by echocardiography. Neurological and cognitive functional tests were performed. Mice were sacrificed at 10 days after ICH for histological and immunohistochemically staining. Compared with WT-sham mice, WT-ICH mice exhibited (1)significantly (P < 0.05) decreased SUMO1 expression in heart tissue, (2)evident neurological and cognitive dysfunction as well as brain white matter deficits, (3)significantly increased cardiac dysfunction, and (4)inflammatory factor expression in the heart and brain. Compared with WT-ICH mice, SUMO1(-/-)-ICH mice exhibited significantly increased: (1)brain hemorrhage volume, worse neurological and cognitive deficits, and increased white matter deficits;(2)cardiac dysfunction and cardiac fibrosis;(3)inflammatory response both in heart and brain tissue. Aged SUMO1-deficient female mice subjected to ICH not only exhibit increased neurological and cognitive functional deficit but also significantly increased cardiac dysfunction and inflammatory cell infiltration into the heart and brain. These data suggest that SUMO1 plays an important role in brain-heart interaction.

关键词： Intracerebral hemorrhage   Wogonin   PPAR-gamma   Hematoma clearance   Anti-inflammation   Anti-oxidative stress  

摘要： Intracerebral hemorrhage (ICH) is a cerebrovascular disease with high mortality and morbidity for which effective treatments are currently lacking. Wogonin is a major flavonoid compound isolated fromScutellaria radix. Accumulating evidence suggests that wogonin plays a crucial role in anti-inflammatory and anti-oxidative stress. Treatment of microglia with nuclear receptor agonists augments the expression of phagocytosis-related genes. However, the neuroprotective effects of wogonin in ICH remain obscure. In this study, we elucidated an innovative mechanism by which wogonin acts to enhance phagocytosis in a murine model of ICH. Wogonin promoted hematoma clearance and improved neurological recovery after ICH by upregulating the expression of Axl, MerTK, CD36, and LAMP2 in perihematomal microglia and BV2 cells. Treatment of a murine model of ICH with wogonin stimulated microglial phagocytosis in vitro. Further, we demonstrated that wogonin dramatically attenuated inflammatory and oxidative stress responses in a murine model of ICH by reducing the expression of pro-inflammatory cytokines and pro-oxidant enzymes such as TNF-alpha, IL-1 beta, and inducible nitric oxide synthase (iNOS) after ICH. The effects of wogonin were abolished by administration of the PPAR-gamma inhibitor GW9662. In conclusion, our data suggest that wogonin facilitates hematoma clearance and neurobehavioral recovery by targeting PPAR-gamma.

关键词： Neuroscience   Psychiatric disorders   Medicine/Public Health   general   Psychiatry   Neurosciences   Behavioral Sciences   Pharmacotherapy   Biological Psychology  

摘要： Functional neurological (conversion) disorder (FND) is a neuropsychiatric condition whereby individuals present with sensorimotor symptoms incompatible with other neurological disorders. Early-life maltreatment (ELM) is a risk factor for developing FND, yet few studies have investigated brain network-trauma relationships in this population. In this neuroimaging-gene expression study, we used two graph theory approaches to elucidate ELM subtype effects on resting-state functional connectivity architecture in 30 patients with motor FND. Twenty-one individuals with comparable depression, anxiety, and ELM scores were used as psychiatric controls. Thereafter, we compared trauma endophenotypes in FND with regional differences in transcriptional gene expression as measured by the Allen Human Brain Atlas (AHBA). In FND patients only, we found that early-life physical abuse severity, and to a lesser extent physical neglect, correlated with corticolimbic weighted-degree functional connectivity. Connectivity profiles influenced by physical abuse occurred in limbic (amygdalar-hippocampal), paralimbic (cingulo-insular and ventromedial prefrontal), and cognitive control (ventrolateral prefrontal) areas, as well as in sensorimotor and visual cortices. These findings held adjusting for individual differences in depression/anxiety, PTSD, and motor phenotypes. In FND, physical abuse also correlated with amygdala and insula coupling to motor cortices. In exploratory analyses, physical abuse correlated connectivity maps overlapped with the AHBA spatial expression of three gene clusters: (i) neuronal morphogenesis and synaptic transmission genes in limbic/paralimbic areas;(ii) locomotory behavior and neuronal generation genes in left-lateralized structures;and (iii) nervous system development and cell motility genes in right-lateralized structures. These circuit-specific architectural profiles related to individual differences in childhood physical abuse burden advance our understanding

关键词： Net revenue   expense ratio   Relative value units   RVU   Downstream revenue  

摘要： Child neurology programs can be net margin generators for children's hospitals. The relative value unit (RVU) expectations for child neurologists are heavily influenced by proceduralists (neurophysiologists, Botox injectors, and so forth) and means in most RVU data sets are not realistic expectations for Evaluation and Management coding, outpatient neurologists. Yet each neurologist has a net revenue/expense ratio of 1.97 for a hospital neurology enterprise, so each of the neurologists generates nearly twice their salary for the hospital. Downstream revenue is even more impressive. Each neurologist generates about $2,000,000.00 in downstream revenue per year.

关键词： headache   guideline   referral   neurology   outpatient   health service delivery  

摘要： Background Headache is a common problem in primary care and one of the main reasons general practitioners (GP) consult the neurology service. We developed an online adult headache guideline (Supporting Information Appendix S1) for the greater Wellington Region as a resource for GP to guide identification of concerning headaches, initiation of prophylactic medications for migraine and management of analgesic overuse headache. Aims To examine the effectiveness of this adult headache guideline in reducing demand on the neurology outpatient service for headache patients that could readily be managed in primary care. Methods We reviewed electronic referrals to Wellington Hospital's neurology department before and after the implementation of the online headache guideline. The primary outcome was the proportion of referrals for headache. Secondary outcomes included proportion of referrals requiring clinic review, rate of pre-referral trial of headache prophylactic medication and medication overuse headache diagnosed at neurological consultation. Results Nine hundred neurology referrals before and 801 referrals after the publication of the online headache guideline were included. There was a statistically significant reduction in proportion of referrals for headache (15.4% vs 11.7%;P = 0.026). There was neither an increased rate of pre-referral adequate prophylactic medication trial (33.8% vs 27.7%;P = 0.320) nor fewer medication overuse headaches diagnosed during the neurology assessment (21.9% vs 25.0%;P = 0.674). Conclusion The launch of an online headache guideline was associated with a reduction in demand on neurology service. Further education could improve the utilisation of this guideline, to avoid delays in prophylactic treatment and reduce the harm of medication overuse.

关键词： paediatric   gut microbiome   intestinal microbiome   review   neuropsychiatric   neurodevelopmental  

摘要： Introduction: The gut-brain axis refers to the bidirectional communication that occurs between the intestinal tract and central nervous system (CNS). Through a series of neural, immune, endocrine, and metabolic signalling pathways, commensal microbiota are able to influence CNS development and neurological function. Alterations in gut microbiota have been implicated in various neuropathologies. The purpose of this review is to evaluate and summarise existing literature assessing the role of specific bacterial taxa on the development of neurodevelopmental, neuropsychiatric, and neurodegenerative pathologies of childhood. We will also discuss microbiota-based therapies dietary interventions and their efficacy. Methods and analysis: We will search PubMed, Cochrane Library, and OVID electronic databases for articles published between January 1980 and February 2021. A search method involving two rounds of reviewing the literature using a three-step method in each round will be performed. Two researchers will be selected, and screen titles and abstracts independently. The full text of selected articles will be assessed against inclusion criteria. Data will be extracted and evaluated using the appropriate Critical Appraisal Skills Programme (CASP) checklist. Ethics and dissemination: Findings from this study will be shared across relevant paediatric neurology and gastroenterology societies and submitted for peer review. This study did not require institutional ethics approval.