关键词： Wilson's disease   Large-scale functional brain networks   Functional magnetic resonance images   Machine learning   Biomarkers  

摘要： Wilson's disease patients with neurological symptoms have motor symptoms and cognitive deficits, including frontal executive, visuospatial processing, and memory impairments. Although the brain structural abnormalities associated with Wilson's disease have been documented, it remains largely unknown how Wilson's disease affects large-scale functional brain networks. In this study, we investigated functional brain networks in Wilson's disease. Particularly, we analyzed resting state functional magnetic resonance images of 30 Wilson's disease patients and 26 healthy controls. First, functional brain networks for each participant were extracted using an independent component analysis method. Then, a computationally efficient pattern classification method was developed to identify discriminative brain functional networks associated with Wilson's disease. Experimental results indicated that Wilson's disease patients, compared with healthy controls, had altered large-scale functional brain networks, including the dorsal anterior cingulate cortex and basal ganglia network, the middle frontal gyrus, the dorsal striatum, the inferior parietal lobule, the precuneus, the temporal pole, and the posterior lobe of cerebellum. Classification models built upon these networks distinguished between neurological WD patients and HCs with accuracy up to 86.9% (specificity: 86.7%, sensitivity: 89.7%). The classification scores were correlated with the United Wilson's Disease Rating Scale measures and durations of disease of the patients. These results suggest that Wilson's disease patients have multiple aberrant brain functional networks, and classification scores derived from these networks are associated with severity of clinical symptoms.

关键词： Neurological pupil index   Neurological worsening   Large hemispheric stroke  

摘要： Background/Objective Cerebral herniation due to brain edema is the major cause of neurological worsening in patients suffering large hemispheric strokes. In this study, we investigated whether quantitative pupillary response could help identify the neurological worsening due to brain swelling in patients with large hemispheric strokes. Methods Quantitative pupillary assessment using an automated pupillometer (NPi-100) was performed between April 2017 and August 2019 for patients suffering large hemispheric strokes. Consecutive pupillary responses were measured every 2 or 4 h as a part of routine clinical care. We compared the mean neurological pupil index (NPi) values, NPi value at the time of neurological deterioration, and percentage change in NPi from the immediate previous value between patients with and without neurological worsening. Results In this study, 2442 quantitative pupillary assessments were performed (n = 30;mean age, 67.9 years;males, 60.0%). Among the included patients, 10 (33.3%) experienced neurological worsening. Patients with neurological worsening had a significantly lower mean value of NPi and a sudden decrease in the NPi value as compared to those without neurological worsening during the whole monitoring period (3.88 +/- 0.65 vs. 4.45 +/- 0.46, P < 0.001;and 29.5% vs. 11.1%, P = 0.006, respectively). All patients with NPi values below 2.8 showed neurological deterioration. Conclusions Quantitative monitoring of the pupillary response using an automated pupillometer could be a useful and noninvasive tool for detecting neurological deterioration due to cerebral edema in large hemispheric stroke patients.

关键词： Aging   Autophagy   Neurodegeneration   Neurological disorder   Polyamine   Spermidine  

摘要： Spermidine is a naturally occurring endogenous polyamine synthesized from diamine putrescine. It is a well-known autophagy inducer that maintains cellular and neuronal homeostasis. Healthy brain development and function are dependent on brain polyamine concentration. Polyamines interact with the opioid system, glutamatergic signaling and neuroinflammation in the neuronal and glial compartments. Among the polyamines, spermidine is found highest in the human brain. Age-linked fluctuations in the spermidine levels may possibly contribute to the impairments in neural network and neurogenesis. Exogenously administered spermidine helps in the treatment of brain diseases. Further, current studies highlight the ability of spermidine to promote longevity by inducing autophagy. Still, the causal neuroprotective mechanism of spermidine in neuronal dysfunction remains unidentified. This review aims to summarize various neuroprotective effects of spermidine related to anti-aging/ anti-inflammatory properties and the prevention of neurotoxicity that helps in achieving beneficial effects in age-related neurological disorder. We also expose the signaling cascades modulated by spermidine which might result in therapeutic action. The present review highlights clinical studies along with in-vivo and in-vitro preclinical studies to provide a new dimension for the therapeutic potential of spermidine in neurological disorders. © 2020 Elsevier Ltd

关键词： autoimmune hepatitis   extrahepatic manifestations   ganglionopathy   sensory ataxia   sensory neuronopathy  

摘要： Background and purpose Neurological manifestations have been identified in the context of autoimmune hepatitis (AIH). Previous case reports highlighted the association between AIH and sensory neuronopathy (SN). Despite that, little is known about the frequency of AIH-related SN and its clinical/neurophysiological profile. Moreover, it is not clear whether SN is an AIH-specific manifestation or related to chronic liver damage. Methods Seventy consecutive AIH patients were enrolled and their characteristics were compared with 52 consecutive patients with chronic active hepatitis B. All subjects underwent clinical and neurophysiological evaluation. Further comparisons were performed between AIH SN and AIH non-SN patients. Results Mean ages and male:female proportions in the AIH and chronic active hepatitis B groups were 42.2 +/- 16.3/51.7 +/- 13.6 years and 14:56/29:23, respectively. The frequencies of carpal tunnel syndrome, radiculopathy and polyneuropathy were similar between groups. In contrast, SN was identified only in AIH patients (5/70 vs. 0/52,P = 0.04);the overall prevalence of AIH-related SN was 7% with an average profile of a woman in her 40s with asymmetric onset of sensory deficits that chronically evolved to disabling proprioceptive ataxia associated with marked dysautonomia. Neurological disability and hepatocellular damage did not follow in parallel. Anti-fibroblast growth factor receptor type 3 antibodies were found in 3/5 (60%) of the patients with AIH-related SN. Clinical or demographic predictors of SN in the context of AIH could not be identified. Conclusion Sensory neuronopathy, but not other peripheral nervous system diseases, is a specific AIH neurological manifestation. It is often disabling and, in contrast to hepatocellular injury, does not respond to immunosuppression.

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： 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： 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： 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.