摘要： "Stem cell tourism," the practice of offering unproven cellular preparations to patients as approved therapy, is rising in neurology. Currently, the experiences of patients and reported complications from these procedures are unknown in the United States. We evaluate academic neurologists' experiences with stem cell tourism and assess perceived competency on discussing this topic with patients. We found a lack of neurologist preparedness to discuss stem cell therapies with patients and an alarming list of unreported complications from these unregulated procedures. We also identified an urgent need for neurologist education and the creation of a national registry for reporting patient complications resulting from experimental stem cell interventions. ANN NEUROL 2020

关键词： Functional neurological disorder   Conversion symptoms   Psychogenic nonepileptic seizures  

摘要： Background: There is a scarcity of reports from limited-resources countries on functional neurological disorder (FND). We therefore carried out this descriptive study from Sudan to highlight the clinical characteristics of patients and the cultural, diagnostic, and management outcome. Method: Of 1000 new referrals and patients seen at a central neuropsychiatric clinic in Khartoum, Sudan, 40 fulfilled the criteria for FND. Subjects were diagnosed by excluding organic illness and confirming psychological distress through neuropsychological assessment and clinical interview. Mood was measured using the Beck Depression Inventory (BDI) and Hospital Anxiety and Depression (HAD) scales. Results: Young unemployed women constituted 60% of our sample. Most subjects presented with psychogenic nonepileptic seizures (825%), speech abnormalities (47.5%), and limb paralysis or weakness was (35%). Associated mood disorder was found in 97.5% of all subjects. However, 95% of our sample showed a remarkable clinical response to combination therapy (antidepressants and psychotherapy). Significance: Patients with FND showed strong evidence of comorbid affective disorders in the form of depression and anxiety disorder. Most patients (95%) responded well to combination therapy with antidepressants and psychotherapy. Sociodemographic correlates of FND in Sudan prove to be consistent with features found in Western cultures, with only minor idiosyncratic characteristics due to local culture. (C) 2020 Elsevier Inc. All rights reserved.

关键词： apoptosis   infection   neurodegenerative disease   stroke   TRAIL   traumatic brain injury  

摘要： Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumour necrosis factor (TNF) superfamily which mainly induces apoptosis of tumour cells and transformed cell lines with no systemic toxicity, whereas they share high sequence homology with TNF and CD95L. These unique effects of TRAIL have made it an important molecule in oncology research. However, the research on TRAIL-related antineoplastic agents has lagged behind and has been limited by the extensive drug resistance in cancer cells. Given the several findings showing that TRAIL is involved in immune regulation and other pleiotropic biological effects in non-malignant cells, TRAIL and its receptors have attracted widespread attention from researchers. In the central nervous system (CNS), TRAIL is highly correlated with malignant tumours such as glioma and other non-neoplastic disorders such as acute brain injury, CNS infection and neurodegenerative disease. Many clinical and animal studies have revealed the dual roles of TRAIL in which it causes damage by inducing cell apoptosis, and confers protection by enhancing both pro- and non-apoptosis effects in different neurological disorders and at different sites or stages. Its pro-apoptotic effect produces a pro-survival effect that cannot be underestimated. This review extensively covers in vitro and in vivo experiments and clinical studies investigating TRAIL. It also provides a summary of the current knowledge on the TRAIL signalling pathway and its involvement in pathogenesis, diagnosis and therapeutics of CNS disorders as a basis for future research.

关键词： Optomotor response   Chlorpyrifos   C-start response   Fathead minnow   Feeding   Early life stage  

摘要： Neuroactive compounds are routinely detected in surface waters at concentrations that pose potential threats to wildlife. Exposure to neurotoxicants can adversely affect exposed organism by altering ecologically-important behaviors (e.g., feeding and predator response) that are likely to have important repercussions for populations. These compounds can elicit behavioral effects at concentrations lower than those that induce overt toxicity as indicated by mortality or decreased growth. Though a wide variety of methods have been employed to assess the behavior of early life stage fish, it is unclear which assays are best suited for identifying ecologically-relevant behavioral changes following exposures to neurotoxicants. The goal of the present study was to promote the use of behavioral assays for assessing the behavioral impacts of exposure to neurotoxic compounds by comparing the performance of different behavioral assays in larval fish. To achieve this goal, the sensitivity and practicality of three behavioral assays (i.e., feeding, optomotor response, and C-start assays) were compared in larval fathead minnows exposed to a known neurotoxicant, chlorpyrifos. There were significant alterations in the performance of fathead minnow larvae in all three behavioral assays in response to a 12-d embryo-larval exposure to chlorpyrifos. However, feeding and C-start were the most practical of the selected assays, as they took less time and allowed for larger samples sizes. Further work to standardize behavioral testing methods, and to link alterations to ecologically-relevant behaviors, will help promote the use of these assays when investigating the potential environmental impacts of neurotoxic compounds. (C) 2020 Elsevier Ltd. All rights reserved.

关键词： Chromodomain helicase DNA binding protein 8   Traumatic brain injury   Wnt   Apoptosis   Autophagy  

摘要： Traumatic brain injury (TBI) and autism spectrum disorder (ASDs) share several same biochemical mechanisms and symptoms, such as learning memory impairments and communication deficits. Chromodomain helicase DNA binding protein 8 (CHD8), a member of the CHD family of ATP-dependent chromatin remodeling factors, is one of the top risk genetic factors in ASDs and is highly associated with Wnt/beta-catenin signaling. Yet, the possible effect of CHD8 on TBI remains poorly understood. In vivo, we found that Chd8 co-localized in neurons, astrocytes, and microglia, but predominantly presented in neurons in the prefrontal cortex, hippocampus, and cortex. Both Chd8 and beta-catenin expression peaked at 12 h and shared the similar change tendency after TBI. Chd8 knockdown inhibited wnt pathway, promoted the activation of apoptosis and autophagy, and caused learning and memory impairments both at normal and TBI condition. In addition, overexpression of Chd8 via 17 beta-estrogen (E2) treatment enhanced wnt signaling pathway and suppressed TBI-induced apoptosis and autophagic activation. In vitro, a significant increase of Chd8 and beta-catenin expression was observed in HT22 cells after lipopolysaccharide (lps) treatment or mechanical injury, respectively. Chd8 knockdown inhibited wnt signaling pathway and increased apoptosis and autophagy activation in lps-stimulated HT22 cells. But activation of wnt signaling inverted the effects of Chd8-siRNA. Our results demonstrated that Chd8 exerted neuroprotection and promoted cognitive recovery through inhibiting apoptosis and autophagy activation following TBI, at least partially by wnt signaling pathway.

关键词： gut microbiota   gut–   brain axis   neurological disorders   probiotics   antibiotics  

摘要： The gut microbiome acts as an integral part of the gastrointestinal tract (GIT) that has the largest and vulnerable surface with desirable features to observe foods, nutrients, and environmental factors, as well as to differentiate commensals, invading pathogens, and others. It is well-known that the gut has a strong connection with the central nervous system (CNS) in the context of health and disease. A healthy gut with diverse microbes is vital for normal brain functions and emotional behaviors. In addition, the CNS controls most aspects of the GI physiology. The molecular interaction between the gut/microbiome and CNS is complex and bidirectional, ensuring the maintenance of gut homeostasis and proper digestion. Besides this, several mechanisms have been proposed, including endocrine, neuronal, toll-like receptor, and metabolites-dependent pathways. Changes in the bidirectional relationship between the GIT and CNS are linked with the pathogenesis of gastrointestinal and neurological disorders;therefore, the microbiota/gut-and-brain axis is an emerging and widely accepted concept. In this review, we summarize the recent findings supporting the role of the gut microbiota and immune system on the maintenance of brain functions and the development of neurological disorders. In addition, we highlight the recent advances in improving of neurological diseases by probiotics/prebiotics/synbiotics and fecal microbiota transplantation via the concept of the gut-brain axis.

关键词： COVID-19   SARS-CoV-2   Neurological manifestations   Systematic review   Inflammation  

摘要： Background Coronavirus disease 2019 (COVID-19) has become a global pandemic, affecting millions of people. However, clinical research on its neurological manifestations is thus far limited. In this study, we aimed to systematically collect and investigate the clinical manifestations and evidence of neurological involvement in COVID-19. Methods Three medical (Medline, Embase, and Scopus) and two preprints (BioRxiv and MedRxiv) databases were systematically searched for all published articles on neurological involvement in COVID-19 since the outbreak. All included studies were systematically reviewed, and selected clinical data were collected for meta-analysis via random-effects. Results A total of 41 articles were eligible and included in this review, showing a wide spectrum of neurological manifestations in COVID-19. The meta-analysis for unspecific neurological symptoms revealed that the most common manifestations were fatigue (33.2% [23.1-43.3]), anorexia (30.0% [23.2-36.9]), dyspnea/shortness of breath (26.9% [19.2-34.6]), and malaise (26.7% [13.3-40.1]). The common specific neurological symptoms included olfactory (35.7-85.6%) and gustatory (33.3-88.8%) disorders, especially in mild cases. Guillain-Barre syndrome and acute inflammation of the brain, spinal cord, and meninges were repeatedly reported after COVID-19. Laboratory, electrophysiological, radiological, and pathological evidence supported neurologic involvement of COVID-19. Conclusions Neurological manifestations are various and prevalent in COVID-19. Emerging clinical evidence suggests neurological involvement is an important aspect of the disease. The underlying mechanisms can include both direct invasion and maladaptive inflammatory responses. More studies should be conducted to explore the role of neurological manifestations in COVID-19 progression and to verify their underlying mechanisms.

关键词： Critical care   Stroke   Cerebral infarction   Intracerebral hemorrhage   Coagulopathy  

摘要： Background Little is known about newly developed stroke in patients admitted to the intensive care unit (ICU). Objective This study aimed to investigate characteristics and outcomes of newly developed stroke in patients admitted to the non-neurological intensive care units (ICU-onset stroke, IOS). Methods A consecutive series of adult patients who were admitted to the non-neurological ICU were included in this study. We compared neurological profiles, risk factors, and mortality rates between patients with IOS and those without IOS. Results Of 18,604 patients admitted to the ICU for non-neurological illness, 218 (1.2%) developed stroke (ischemic, n = 182;hemorrhagic, n = 36). The most common neurological presentation was altered mental status (n = 149), followed by hemiparesis (n = 55), and seizures (n = 28). The most common etiology of IOS was cardioembolism (50% [91/182]) for ischemic IOS and coagulopathy (67% [24/36]) for hemorrhagic IOS. In multivariable analysis, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (adjusted odds ratio [AOR] = 1.04, 95% CI = 1.03-1.06, P < 0.001), prothrombin time (AOR = 0.99, 95% CI = 0.98-0.99, P = 0.013), cardiovascular surgery (AOR = 1.84, 95% CI = 1.34-2.50, P < 0.001), mechanical ventilation (AOR = 6.75, 95% CI = 4.87-9.45, P < 0.001), and extracorporeal membrane oxygenation (AOR = 2.77, 95% CI = 1.62-4.55, P < 0.001) were related to the development of IOS. Stroke was associated with increased 3-month mortality after hospital discharge (AOR, 2.20;95% CI, 1.58-3.05;P < 0.001), after adjustment for APACHE II and comorbidities. Conclusions Patients who developed IOS had characteristics of initial critical illness and managements performed in the ICU as well as neurological presentations. The occurrence of IOS was related to high morbidity and mortality.

关键词： Cardiac arrest   Prognostication   Guideline algorithm   Prognostic accuracy   Coma  

摘要： Purpose To assess the performance of a 4-step algorithm for neurological prognostication after cardiac arrest recommended by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM). Methods Retrospective descriptive analysis with data from the Target Temperature Management (TTM) Trial. Associations between predicted and actual neurological outcome were investigated for each step of the algorithm with results from clinical neurological examinations, neuroradiology (CT or MRI), neurophysiology (EEG and SSEP) and serum neuron-specific enolase. Patients examined with Glasgow Coma Scale Motor Score (GCS-M) on day 4 (72-96 h) post-arrest and available 6-month outcome were included. Poor outcome was defined as Cerebral Performance Category 3-5. Variations of the ERC/ESICM algorithm were explored within the same cohort. Results The ERC/ESICM algorithm identified poor outcome patients with 38.7% sensitivity (95% CI 33.1-44.7) and 100% specificity (95% CI 98.8-100) in a cohort of 585 patients. An alternative cut-off for serum neuron-specific enolase, an alternative EEG-classification and variations of the GCS-M had minor effects on the sensitivity without causing false positive predictions. The highest overall sensitivity, 42.5% (95% CI 36.7-48.5), was achieved when prognosticating patients irrespective of GCS-M score, with 100% specificity (95% CI 98.8-100) remaining. Conclusion The ERC/ESICM algorithm and all exploratory multimodal variations thereof investigated in this study predicted poor outcome without false positive predictions and with sensitivities 34.6-42.5%. Our results should be validated prospectively, preferably in patients where withdrawal of life-sustaining therapy is uncommon to exclude any confounding from self-fulfilling prophecies.