关键词： HERV   multiple sclerosis   regulation   viral transactivation   epigenetics  

摘要： Human endogenous retroviruses (HERVs) are remnants of ancient retroviral germline infections. Most HERV sequences are silenced in somatic cells, but interest is emerging on the involvement of HERV derived transcripts and proteins in human physiology and disease. A HERV-W encoded protein, syncytin-1, has been co-opted into fetal physiology, where it plays a role in trophoblast formation. Altered HERV transcription and expression of HERV derived proteins are associated with various cancer types and neurological diseases such as multiple sclerosis (MS). The implication of HERVs as potential mediators of both health and disease suggests important roles of regulatory mechanisms and alterations of these in physiological and pathological processes. The regulation of HERV sequences is mediated by a wide variety of mechanisms, and the focus of this review is on selected aspects of these, including epigenetic mechanisms such as CpG methylation and histone modifications of the HP1-H3K9me axis, viral transactivation events, and regulatory perspectives of transient stimuli in the microenvironment. Increasing knowledge of the regulation of HERV sequences will not only contribute to the understanding of complex pathogeneses, but also may pinpoint potential targets for better diagnosis and treatment in complex diseases as MS.

关键词： COVID-19   SARS-CoV-2   Coronavirus   beta-coronavirus   Neurological symptoms  

摘要： Object The novel severe acute respiratory syndrome (SARS)-CoV-2 outbreak has been declared a pandemic in March, 2020. An increasing body of evidence suggests that patients with the coronavirus disease (COVID-19) might have a heterogeneous spectrum of neurological symptoms Methods A systematic search of two databases was performed for studies published up to May 29th, 2020. PRISMA guidelines were followed. Results We included 19 studies evaluating 12,157 patients with laboratory-confirmed COVID-19 infections. The median age of patients was 50.3 (IQR 11.9), and the rate of male patients was 50.6% (95% CI 49.2-51.6%). The most common reported comorbidities were hypertension and diabetes (31.1%, 95% CI 30-32.3% and 13.5%, 95% CI 12.3-14.8%, respectively). Headache was reported in 7.5% of patients (95% CI 6.6-8.4%), and dizziness in 6.1% (95% CI 5.1-7.1%). Hypo/anosmia, and gustatory dysfunction were reported in 46.8 and 52.3%, of patients, respectively. Symptoms related to muscular injury ranged between 15 and 30%. Three studies reported radiological confirmed acute cerebrovascular disease in 2% of patients (95% CI 1.6-2.4%). Conclusions These data support accumulating evidence that a significant proportion of patients with COVID-19 infection develop neurological manifestations, especially olfactory, and gustatory dysfunction. The pathophysiology of this association is under investigation and warrants additional studies, Physicians should be aware of this possible association because during the epidemic period of COVID-19, early recognition of neurologic manifestations otherwise not explained would raise the suspect of acute respiratory syndrome coronavirus 2 infection.

关键词： COVID-19   Neurologic comorbidity   Network biology   Disease-gene interaction   Hub genes   Drug repurposing  

摘要： Although COVID-19 largely causes respiratory complications, it can also lead to various extrapulmonary manifestations resulting in higher mortality and these comorbidities are posing a challenge to the health care system. Reports indicate that 30-60% of patients with COVID-19 suffer from neurological symptoms. To understand the molecular basis of the neurologic comorbidity in COVID-19 patients, we have investigated the genetic association between COVID-19 and various brain disorders through a systems biology-based network approach and observed a remarkable resemblance. Our results showed 123 brain-related disorders associated with COVID-19 and form a high-density disease-disease network. The brain-disease-gene network revealed five highly clustered modules demonstrating a greater complexity of COVID-19 infection. Moreover, we have identified 35 hub proteins of the network which were largely involved in the protein catabolic process, cell cycle, RNA metabolic process, and nuclear transport. Perturbing these hub proteins by drug repurposing will improve the clinical conditions in comorbidity. In the near future, we assumed that in COVID-19 patients, many other neurological manifestations will likely surface. Thus, understanding the infection mechanisms of SARS-CoV-2 and associated comorbidity is a high priority to contain its short- and long-term effects on human health. Our network-based analysis strengthens the understanding of the molecular basis of the neurological manifestations observed in COVID-19 and also suggests drug for repurposing.

摘要： This commentary is on the original article by Hov et al. on pages 537–544 of this issue.

摘要： Background: Carotid endarterectomy (CEA) prevents the occurrence of stroke in the future, although its efficacy depends on the detection and control of high perioperative risk factors. We aimed to analyze the association between preoperative neurological deficit and the 30-day risk of major adverse cardiovascular events (MACEs) in CEA with selective shunting for symptomatic carotid stenosis. Methods: We assessed 653 patients who underwent CEA with selective shunting for symptomatic carotid stenosis between August 2011 and August 2019. The primary outcomes of the study were the occurrence of MACEs, defined as stroke (ischemic stroke or cerebral hemorrhage), all-cause mortality, and myocardial infarction during the perioperative period after CEA. Baseline patient characteristics were analyzed to identify factors associated with perioperative (<30 days) MACEs. Multivariable logistic regression models were used to estimate the association between preoperative modified Rankin Scale (mRS) and the 30-day risk of MACEs. Interaction and stratified analyses were conducted according to age, drinking, history of hypertension and coronary artery disease, and surgical side. Results: The mean age of patients was 68.7 +/- 9.1 years, and 86.4% were men. The 30-day MACEs rate was 2.5%. In univariate logistic regression, histories of coronary artery disease (odds ratio (OR), 2.57 [95% confidence interval (CI), 1.04-6.34]), a severe contralateral carotid stenosis or occlusion (OR, 4.52 [95% CI, 1.84-11.11]), and a poor neurological deficit (mRS >= 3 versus mRS < 3: OR, 3.78 [95% CI, 1.21-11.82]) were associated with higher primary outcome rates. A history of hypertension did not increase the risk of MACEs (OR, 0.37 [95% CI, 0.15- 0.89]). In the multivariable regression analysis, poor neurological deficit was associated with a higher risk of the MACEs within 30 days (mRS >= 3 versus mRS < 3: 11.1% vs. 2.0%, adjusted OR 5.70 [95% CI, 1.50-21.60]). The interaction analysis revealed no int

关键词： Gaucher disease type 3   Neuronopathic form   Ambroxol   Pharmacological chaperone  

摘要： Gaucher disease type 3 (GD3) is a severely debilitating disorder characterized by multisystemic manifestations and neurodegeneration. Enzyme replacement therapy alleviates visceral signs and symptoms but has no effect on neurological features. Ambroxol has been suggested as an enzyme enhancement agent. Some studies have confirmed its effectiveness in preventing the progression of neurological manifestations of neuronopathic Gaucher disease. In this study, we report two GD3 siblings in whom ambroxol combined with enzyme replacement therapy was initiated at different stages of the disease. We demonstrate the enzyme enhancement effect of ambroxol on L444P/H225Q;D409H glucocerebrosidase activity through results of fibroblast studies and long-term clinical outcomes of the two patients. The sibling diagnosed at the age of four-and-a-half years with significant neurological involvement manifested relatively rapid improvement on ambroxol treatment, followed by stabilization of further course. The younger sibling, in whom the treatment was started at seven weeks, displayed attention deficit and low average cognitive functioning at the age of seven years, but did not manifest other neurological symptoms. The difference in neurological outcomes indicates that ambroxol delayed or even halted the evolution of neurological manifestations in the younger sibling. This observation suggests that early initiation of ambroxol treatment may arrest neurological involvement in some GD3 patients. (c) 2021 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

关键词： Adult brain   Neurogenesis   Hippocampus   Direct reprogramming   Epigenetics   Injury   Microglia  

摘要： Neural stem cells (NSCs) in the adult hippocampus generate new neurons via a process referred to as neurogenesis, supporting cognitive functions. Since altered neurogenesis has been reportedly associated with several diseases such as epilepsy, the molecular basis of NSC activity is an important focus in the study of neurogenesis. Furthermore, facilitation of neurogenesis in the injured brain would be an ideal approach to replenish lost neurons for damage recovery. However, natural neurogenesis by endogenous NSCs in the adult brain is insufficient for complete recovery after severe injury. Recent advances in understanding forced neurogenesis from brain-resident non-neuronal cells by direct reprogramming and clearing hurdles to achieve it have improved the ability to replace damaged neurons in the brain. In this review, we describe molecular mechanisms underlying natural and forced neurogenesis, and discuss future directions for treatments of diseases in the central nervous system. (c) 2020 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

关键词： cohort study <   research methods   functional disorders <   psychiatric disorders <   neurological disorders   psychiatric disorders <   neurological disorders  

摘要： Background Functional neurological disorders (FND) represent a significant proportion of presentations to outpatient adult neurology services. There is little information relating to patients presenting to acute inpatient care. Methods We identified patients presenting as acute admissions with FND to Christchurch Hospital, Christchurch, New Zealand, from 2016 to 2018. We analyzed relevant demographic and clinical data from electronic records and measured incidence of presentation to secondary care and healthcare utilization. Results One hundred sixty-two patients presented on 173 occasions with FND, representing 9% of all admissions to the neurology service during the 3-year study period. The mean age was 40 (SD 17) years, 111 (69%) patients were female and the median length of stay was 3 (IQR 2-4) days. A total of 92 computed tomography brain scans, 77 magnetic resonance imaging brain scans and 42 electroencephalograms were carried out. On 22 (13%) occasions, patients were referred for outpatient psychological therapy. In the 3 years prior to each patient's last presentation in the study period, these 162 patients had a total of 671 presentations to the emergency department. Healthcare demand did not decrease after the index admission. The rate of acute inpatient admission for FND was 10 per 100,000 per year for the total Christchurch Hospital catchment, 6/100,000/year in rural areas, and 11/100,000/year in urban areas. Conclusion FND represented almost 1 in 10 acute neurology admissions with significant inpatient healthcare resource utilization.

关键词： Outcomes research   Spinal cord diseases  

摘要： Study design Retrospective multicenter study. Objectives To identify the usefulness of the baseline severity of myelopathy for predicting surgical outcomes for cervical spondylotic myelopathy (CSM). Setting Seventeen institutions in Japan. Methods This study included 675 persons with CSM who underwent posterior decompression. According to baseline severity, the individuals were divided into the mild (Japanese Orthopaedic Association [JOA] score >= 14.5), moderate (JOA score = 10.5-14), and severe (JOA score <= 10) groups. Surgical outcomes and clinical variables were compared between the groups. Logistic regression analysis was used to develop a prediction model for unsatisfactory symptom state (postoperative JOA score <= 14, residual moderate or severe myelopathy). Results The mean (+/- standard deviation) age was 67 +/- 12 years. The participants in the severe group were older than those in the mild group. Postoperative JOA scores were higher in the mild group than in the severe group. According to multivariate logistic regression analysis, the prediction model included preoperative JOA scores (odds ratio [OR] 0.60;95% confidence interval [CI] 0.55-0.67) and age (OR 1.06, 95% CI 1.04-1.08). On the basis of the model, a representative combination of the thresholds to maximize the value of "sensitivity - (1 - specificity)" demonstrated a preoperative JOA score of 11.5 as a predictor of postoperative unsatisfactory symptom state in people around the mean age of the study cohort (67 years). Conclusions The combination of the baseline severity of myelopathy and age can predict postoperative symptom states after posterior decompression surgery for CSM.