关键词： Ferroptosis   Epigenetics   HDAC   Transglutaminase   HIF prolyl hydroxylase  

摘要： A major thrust of our laboratory has been to identify how physiological stress is transduced into transcriptional responses that feed back to overcome the inciting stress or its consequences, thereby fostering survival and repair. To this end, we have adopted the use of an in vitro model of ferroptosis, a caspase-independent, but iron dependent form of cell death (Dixon et al., 2012;Ratan, 2020). In this review, we highlight three distinct epigenetic targets that have evolved from our studies and which have been validated in vivo studies. In the first section, we discuss our studies of broad, pan-selective histone deacetylase (HDAC) inhibitors in ferroptosis and how these studies led to the validation of HDAC inhibitors as candidate therapeutics in a host of disease models. In the second section, we discuss our studies that revealed a role for transglutaminase as an epigenetic modulator of proferroptotic pathways and how these studies set the stage for recent elucidation of monoamines as post translation modifiers of histone function. In the final section, we discuss our studies of iron-, 2-oxoglutarate-, and oxygen-dependent dioxygenases and the role of one family of these enzymes, the HIF prolyl hydroxylases, in mediating transcriptional events necessary for ferroptosis in vitro and for dysfunction in a host of neurological conditions. Overall, our studies highlight the importance of epigenetic proteins in mediating prodeath and prosurvival responses to ferroptosis. Pharmacological agents that target these epigenetic proteins are showing robust beneficial effects in diverse rodent models of stroke, Parkinson's disease, Huntington's disease, and Alzheimer's disease.

关键词： functional neurological disorder   paediatric rehabilitation   psychogenic   physical therapy   physiotherapy   somatoform   somatic  

摘要： Aim Children and adolescents with functional neurological disorder (FND) present with physical impairment and mental health comorbidities. Specialist physiotherapy programs for treating FND have been developed over the last two decades. This article reports outcome data from three cohorts of children treated with a multidisciplinary rehabilitation intervention - the Mind-Body Program - in which a psychologically informed physiotherapy intervention, known as thewellness approach to physiotherapy, was a key component. Methods For three cohorts of children (n= 57,n= 60 andn= 25, respectively) treated in the Mind-Body Program, data about functional impairment and mental health concerns were collected at presentation and at follow-up (4 years, 12 months and 18 months, respectively). Results Outcome data show that FND symptoms resolved in 54/57 (95%), 51/60 (85%) and 22/25 (88%) of children in the three cohorts, and that 31/57 (61%), 32/60 (53%) and 13/25 (52%) of children returned to full health and to full-time school attendance. Changes in Global Assessment of Function (GAF) were significant (t(54) = 21.60,P < 0.001;t(55) = 9.92,P < 0.001;t(24) = 6.51,P < 0.001). Outcomes were less favourable for children with chronic FND symptoms at presentation;those whose comorbid mental health disorders or other (comorbid) functional somatic symptoms did not resolve;and those who subsequently developed chronic mental health problems. Conclusions Implementation of a multidisciplinary rehabilitation intervention - with psychologically informed physiotherapy as one of the key treatment components - resulted in resolution of FND symptoms and return to health and well-being in the large majority of patients.

关键词： Children   Tracheal resection   Anteflexion   Cervical myelopathy   Hirayama disease  

摘要： Constant neck flexion has been considered crucial to reducing anastomotic tension after tracheal resection. However, in rare cases, anteflexion can cause cervical cord damage, leading to acute neurological disorders such as tetraplegia. Here, we report a case of 5-year-old boy presenting with acute neurological disorder triggered by a chin-to-chest position over 4 days of deep sedation after cricotracheal resection. The radiological findings would suggest a mechanism similar to Hirayama disease, in which a shift of the dura leads to chronic muscular weakness and atrophy in young populations.

关键词： GARS   aaRS   CMT   SMA   dHMN   ALS  

摘要： Aminoacyl-RNA synthetases (aaRSs) are among the key enzymes of protein biosynthesis. They are responsible for conducting the first step in the protein biosynthesis, namely attaching amino acids to the corresponding tRNA molecules both in cytoplasm and mitochondria. More and more research demonstrates that mutations in the genes encoding aaRSs lead to the development of various neurodegenerative diseases, such as incurable Charcot-Marie-Tooth disease (CMT) and distal spinal muscular atrophy. Some mutations result in the loss of tRNA aminoacylation activity, while other mutants retain their classical enzyme activity. In the latter case, disease manifestations are associated with additional neuron-specific functions of aaRSs. At present, seven aaRSs (GlyRS, TyrRS, AlaRS, HisRS, TrpRS, MetRS, and LysRS) are known to be involved in the CMT etiology with glycyl-tRNA synthetase (GlyRS) being the most studied of them.

关键词： COVID-19   SARS-CoV-2   Neurological   Symptoms   manifestations   Tunisia  

摘要： Background A wide range of neurological manifestations has been described in COVID-19. Methods In this nationwide retrospective observational study, patients in Tunisia diagnosed with COVID-19 between the 2nd of March and the 16th of May 2020 were contacted by telephone. We collected demographic and clinical data and specified characteristics and evolution of main neurological symptoms. Results Of 1034 confirmed COVID-19 patients, 646 were included (mean age 42.17 years old) and 466 (72.1%) had neurological symptoms. Neurological symptoms were isolated 22.7% (n = 106). Headache was the most frequent neurological symptom (n = 279, 41.1%): mainly frontotemporal (n = 143, 51.1%) and mild or moderate (n = 165, 59.1%). When associated with fever (n = 143, 51.3%), headache was more likely to be severe and present at onset. Recovery was reported in 83.2%. Smell and taste impairment were found in 37.9% (n = 245) and 36.8% (n = 238) respectively. Among them, 65.3% (156/239) were anosmic and 63.2% (146/231) were ageusic. A complete improvement was found in 72.1% (174/240) of smell impairment and in 76.8% (179/233) of taste impairment. Myalgia (n = 241, 37.3%) and sleep disturbances (n = 241, 37.3%) were also frequent. Imported cases had more neurological symptoms (p = 0.001). In 14.5%, neurological symptoms preceded the respiratory signs (RS). RS were associated with more frequent (p = 0.006) and numerous (p < 0.001) neurological symptoms. Conclusions Neurological symptoms in COVID-19 are frequent, can be isolated and present at onset. A total recovery is the most recorded outcome. RS are predictive of neurological symptoms. Studies in to virus and host genetics should be considered to understand the different phenotypes.

关键词： brain neoplasms   germinoma   hypopituitarism   pediatrics  

摘要： Background: Intracranial pure germinoma is a rare extragonadal neoplasm. Affected patients may have motor impairment, visual disturbance, neurological signs, and endocrine disorder, depending on the size and location of the tumor. This study investigated and analyzed patients' demographic data and neuroimaging, clinical, laboratory, and endocrinological findings. Methods: We performed a retrospective chart review of 49 children diagnosed with pure germinoma in Taiwan from 1990 to 2018. The initial clinical presentation, tumor markers (beta-hCG, alpha fetoprotein, and carcinoembryonic antigen), pituitary function, and brain images were reviewed and analyzed. Results: This study included 49 patients (37 boys and 12 girls). Their ages ranged from 7.5 to 17.9 years, and the mean age at diagnosis was 13.6 years. Initial symptoms included visual disturbance (n = 23, 47.9%), motor impairment (n = 20, 40.8%), polyuria (n = 20, 40.8%), headache (n = 17, 34.7%), dizziness or vertigo (n = 14, 28.6%), nausea/vomiting (n = 13, 26.5%), and short stature (n = 8, 18.2%). Laboratory data indicated growth hormone deficiency or low IGF-1 levels (n = 18, 85.7%), adrenal insufficiency (n = 21, 77.8%), central diabetes insipidus (n = 27, 55.1%), central hypothyroidism (n = 15, 48.4%), and hypogonadotropic hypogonadism (n = 4, 44.4%). Conclusion: Intracranial pure germinomas may initially manifest as neurological symptoms or endocrinological findings at diagnosis. As endocrinologic presentation is related to delayed diagnosis, clinicians should be aware of patients with such complaints. Laboratory data should be surveyed carefully, and neuroimaging must be considered if the result is abnormal. Copyright (C) 2020, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC.

关键词： Brain-computer interface   Virtual reality   Neurological diseases   Rehabilitation  

摘要： Background: The traditional rehabilitation for neurological diseases lacks the active participation of patients, its process is monotonous and tedious, and the effects need to be improved. Therefore, a new type of rehabilitation technology with more active participation combining brain-computer interface (BCI) with virtual reality (VR) has developed rapidly in recent years and has been used in rehabilitation in neurological diseases. Objectives: This narrative review analyzed and characterized the development and application of the new training system (BCI-VR) in rehabilitation of neurological diseases from the perspective of the BCI paradigm, to provide a pathway for future research in this field. Methods: The review involved a search of the Web of Science-Science Citation Index/Social Sciences Citation Index and the China National Knowledge Infrastructure databases;39 papers were selected. Advantages and challenges of BCI-VR - based neurological rehabilitation were analyzed in detail. Results: Most BCI-VR studies included could be classified by 3 major BCI paradigms: motor imagery, P300, and steady-state visual-evoked potential. Integrating VR scenes into BCI systems could effectively promote the recovery process from nervous system injuries as compared with traditional methods. Conclusion: As compared with rehabilitation based on traditional BCI, rehabilitation based on BCI-VR can provide better feedback information for patients and promote the recovery of brain function. By solving the challenges and continual development, the BCI-VR system can be broadly applied to the clinical treatment of various neurological diseases. (C) 2020 Elsevier Masson SAS. All rights reserved.

关键词： Spinal astrocytoma   Intramedullary tumor   Spinal glioma  

摘要： Introduction Primary malignant spinal astrocytomas present rare oncological entities with limited median survival and rapid neurological deterioration. Evidence on surgical therapy, adjuvant treatment, and neurological outcome is sparse. We aim to describe the treatment algorithm and clinical features on patients with infiltrating intramedullary astrocytomas graded WHO II-IV. Methods The following is a multicentered retrospective study of patients treated for spinal malignant glioma WHO II-IV in five high-volume neurosurgical departments from 2008 to 2019. Pilocytic astrocytomas were excluded. We assessed data on surgical technique, perioperative neurological status, adjuvant oncological therapy, and clinical outcome. Results 40 patients were included (diffuse astrocytoma WHO II n = 11, anaplastic astrocytoma WHO III n = 12, WHO IV n = 17). Only 40% were functionally independent before surgery, most patients presented with moderate disability (47.5%). Most patients underwent a biopsy (n = 18, 45%) or subtotal tumor resection (n = 15, 37.5%), and 49% of the patients deteriorated after surgery. Patients with WHO III and IV tumors were treated with combined radiochemotherapy. Median overall survival (OS) was 46.5 months in WHO II, 25.7 months in WHO III, and 7.4 months in WHO IV astrocytomas. Preoperative clinical status and WHO significantly influenced the OS, and the extent of resection did not. Conclusion Infiltrating intramedullary astrocytomas WHO II-IV present rare entities with dismal prognosis. Due to the high incidence of surgery-related neurological impairment, the aim of the surgical approach should be limited to obtaining the histological tissue via a biopsy or, tumor debulking in cases with rapidly progressive severe preoperative deficits.

关键词： Residency   Wellness   Recruitment   Match  

摘要： Background: Medical education, residency training, and the structure of child neurology residency training programs are evolving. We sought to evaluate how training program selection priorities of child neurology residency applicants have changed over time. Methods: An electronic survey was sent to child neurology residents and practicing child neurologists via the Professors of Child Neurology distribution list in the summer of 2018. It was requested that the survey be disseminated to current trainees and alumni of the programs. The survey consisted of seven questions assessing basic demographics and a list of factors applicants consider when choosing a residency. Results: There were 284 responses with a higher representation of individuals matriculating into residency in the last decade. More recent medical school graduates had a lower probability of considering curriculum as an important factor for residency selection (odds ratio [OR], 0.746;95% confidence interval [95% CI], 0.568 to 0.98;P = 0.035) and higher priority placed on interaction with current residents over the course of the interview day (OR, 2.207;95% CI, 1.486 to 3.278;P < 0.0001), sense of resident happiness and well-being (OR, 2.176;95% CI, 1.494 to 3.169;P < 0.0001), and perception of city or geography of the residency program (OR, 1.710;95% CI, 1.272 to 2.298;P < 0.001). Conclusions: Over time, child neurology residency applicants are putting more emphasis on quality of life factors over curriculum. To accommodate these changes, child neurology residency programs should prioritize interactions with residents during the interview process and resident wellness initiatives throughout residency training. (C) 2020 Elsevier Inc. All rights reserved.

摘要： 《国际神经病学神经外科学杂志》创刊于1974年,由教育部主管,中南大学、中南大学湘雅医院主办。是目前国内唯一一本同时涵盖神经病学和神经外科学的专业学术期刊。本刊为"中国科技核心期刊(中国科技论文统计源期刊)",并且进入"《中国高质量科技期刊分级目录》T3区"。国内外公开发行,