关键词： Medicine/Public Health   general   Pediatrics   Pediatric Surgery  

摘要： Background Severe neonatal hyperbilirubinemia has been known to cause the clinical syndrome of kernicterus and a milder one the syndrome of bilirubin-induced neurologic dysfunction (BIND). BIND clinically manifests itself after the neonatal period as developmental delay, cognitive impairment, and related behavioral and psychiatric disorders. The complete picture of BIND is not clear. Methods The Gunn rat is a mutant strain of the Wistar rat with the BIND phenotype, and it demonstrates abnormal behavior. We investigated serotonergic dysfunction in Gunn rats by pharmacological analyses and ex vivo neurochemical analyses. Results Ketanserin, the 5-HT2AR antagonist, normalizes hyperlocomotion of Gunn rats. Both serotonin and its metabolites in the frontal cortex of Gunn rats were higher in concentrations than in control Wistar rats. The 5-HT2AR mRNA expression was downregulated without alteration of the protein abundance in the Gunn rat frontal cortex. The TPH2 protein level in the Gunn rat raphe region was significantly higher than that in the Wistar rat. Conclusions It would be of value to be able to postulate that a therapeutic strategy for BIND disorders would be the restoration of brain regions affected by the serotonergic dysfunction to normal operation to prevent before or to normalize after onset of BIND manifestations. Impact We demonstrated serotonergic dysregulation underlying hyperlocomotion in Gunn rats. This finding suggests that a therapeutic strategy for bilirubin-induced neurologic dysfunction (BIND) would be the restoration of brain regions affected by the serotonergic dysfunction to normal operation to prevent before or to normalize after the onset of the BIND manifestations. Ketanserin normalizes hyperlocomotion of Gunn rats. To our knowledge, this is the first study to demonstrate a hyperlocomotion link to serotonergic dysregulation in Gunn rats.

摘要： This commentary is on the original article by Diskin et al. on pages 200–208 of this issue.

关键词： Brain   Ischemia   Reperfusion   Hyperglycemia   Inflammation   Oxidative stress  

摘要： Persons with type 1 diabetes have an increased risk of stroke compared with the general population. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a neuropeptide that has protective effects against ischemia/reperfusion (I/R) induced organ damages. In this study, we aimed to investigate the neuroprotective role of this peptide on I/R induced brain damage after experimental stroke associated with hyperglycemia using C57BL/6J Ins2(Akita/+) mice. Experimental stroke was induced by blocking the right middle cerebral artery for 2 h with reperfusion for 2 and 22 h, respectively using the intraluminal method. Animals were treated intraperitoneally with or without alpha-MSH at 1 h after ischemia and 1 h after reperfusion. Significantly higher survival rate and lower neurological scores were recorded in animals injected with alpha-MSH. Similarly, neuron death, glial cells activation as well as oxidative and nitrosative stress were significantly decreased in alpha-MSH treated group. Relative intensities of matrix metallopeptidases 9, cyclooxygenase 2 and nuclear factor-kappa B were significantly decreased while intensities of Akt, heme oxygenase (HO) 1, HO-2 and B-cell lymphoma 2 were significantly increased after alpha-MSH treatment. In addition, gene expressions of monocarboxylate transporter (MCT) 1, MCT-2 and activity-regulated cytoskeleton-associated protein were significantly higher in brain samples treated with alpha-MSH, suggesting this peptide may have role in neuron survival by an involvement of lactate metabolism. In conclusion, alpha-MSH is neuroprotective under hyperglycemic condition against I/R induced brain damage by its anti-inflammatory, anti-oxidative and anti-apoptotic properties. The use of alpha-MSH analogues may be potential therapeutic agents for diabetic stroke.

关键词： Neural Stem/Progenitor Cells   microRNAs   Neurogenesis   Regenerative Medicine   miR-17 similar to 92   Proliferation   Differentiation  

摘要： miR-17 similar to 92, an miRNA family containing three paralogous polycistronic clusters, was initially considered as an oncogene and was later demonstrated to trigger various physiological and pathological processes. Emerging evidence has implicated miR-17 similar to 92 family as a master regulator of neurogenesis. Through targeting numerous genes that affect cell cycle arrest, stemness deprivation, and lineage commitment, miR-17 similar to 92 family controls the proliferation and neuronal differentiation of neural stem/progenitor cells in both developmental and adult brains. Due to the essential roles of miR-17 similar to 92 family, its misexpression is widely associated with acute and chronic neurological disorders by attenuating neurogenesis and facilitating neuronal apoptosis. The promising neurogenic potential of miR-17 similar to 92 family also makes it a promising "medicine" to activate the endogenous and exogenous regenerative machinery, thus enhance tissue repair and function recovery after brain injury. In this review, we focus on the recent progress made toward understanding the involvement of miR-17 similar to 92 family in regulating both developmental and adult neurogenesis, and discuss the regenerative potential of miR-17 similar to 92 family in treating neurological disorders.

关键词： Multiple sclerosis   Functional neurological disorder   Conversion disorder   Psychogenic   Misdiagnosis  

摘要： Multiple sclerosis (MS) and functional neurological disorder (FND) are both diagnostically challenging conditions which can present with similar symptoms. We systematically reviewed the literature to identify patients with MS who were misdiagnosed with FND, patients with FND who were misdiagnosed with MS, and reports of patients with both conditions. In addition to FND, we included studies of patients with other functional and psychiatric disorders where these caused symptoms leading to investigation for or a diagnosis of MS, which in a different context would likely have been labeled as FND. Our review suggests that MS is one of the most common causes of misdiagnosis of FND and vice versa. We discuss the clinical errors that appear to result in misdiagnoses, such as over-reliance on psychiatric comorbidity when making a diagnosis of FND or over-reliance on neuroimaging for the diagnosis of MS, and practical ways to avoid them. Comorbidity between these two conditions is also likely common, has been poorly studied, and adds complexity to diagnosis and treatment in patients with both MS and FND. Misdiagnosis and comorbidity in a landscape of emerging evidence-based treatments for both MS and FND are issues not only of clinical importance to the care of these patients, but also to treatment trials, especially of MS, where FND could be a hidden confounder.

关键词： Data length   Dynamic cerebral autoregulation   Transfer function analysis   Invasive arterial blood pressure   Neurological intensive care unit  

摘要： Background Cerebral autoregulation plays an important role in safeguarding adequate cerebral perfusion and reducing the risk of secondary brain injury, which is highly important for patients in the neurological intensive care unit (neuro-ICU). Although the consensus white paper suggests that a minimum of 5 min of data are needed for assessing dynamic cerebral autoregulation with transfer function analysis (TFA), it remains unknown if the length of these data is valid for patients in the neuro-ICU, of whom are notably different than the general populations. We aimed to investigate the effect of data length using transcranial Doppler ultrasound combined with invasive blood pressure measurement for the assessment of dynamic cerebral autoregulation in patients in the neuro-ICU. Methods Twenty patients with various clinical conditions (severe acute encephalitis, ischemic stroke, subarachnoid hemorrhage, brain injury, cerebrovascular intervention operation, cerebral hemorrhage, intracranial space-occupying lesion, and toxic encephalopathy) were recruited for this study. Continuous invasive blood pressure, with a pressure catheter placed at the radial artery, and bilateral continuous cerebral blood flow velocity with transcranial Doppler ultrasound were simultaneously recorded for a length of 10 min for each patient. TFA was applied to derive phase shift, gain, and coherence function at all frequency bands from the first 2, 3, 4, 5, 6, 7, 8, 9, and 10 min of the 10-min recordings in each patient on both hemispheres. The variability in the autoregulatory parameters in each hemisphere was investigated by repeated measures analysis of variance. Results Forty-one recordings (82 hemispheres) were included in the study. According to the critical values of coherence provided by the Cerebral Autoregulation Research Network white paper, acceptable rates for the data were 100% with a length >= 7 min. The final analysis included 68 hemispheres. The effects of data length on trends in

关键词： Neurodevelopmental disorders   Paediatric neurological disorders   Paediatrics   Medicine/Public Health   general   Pediatrics   Pediatric Surgery  

摘要： Global estimates show that 10-20% of persons express developmental disability. During critical and sensitive periods of developmental neuroplasticity over the first 1000 days, adverse gene-environment interactions are likely to contribute to permanent life-long disabilities and early mortality. This article describes fetal-neonatal neurology (FNN) program development that integrates vertical and horizontal diagnostic perspectives. Trimester-specific conditions to the maternal-placental-fetal triad begin at conception, followed by pediatric patient care over the first two years of life to address changing phenotypic form and function. While fetal and neonatal neurology trainees prepare to offer person-centric healthcare, population-based considerations address obstacles to optimal health relevant to resource-rich and poor nations. Maternal and pediatric care practices over the first 1000 days underscore equitable health policy. Global initiatives apply geographic distance, biosocial dynamics, and cultural differences to developmental origins and life-course theories, to more effectively reduce disease burden over the life continuum.

关键词： muscle synergies   whole body FES   neurological patients  

摘要： Background: Neurological diseases and traumas are major factors that may reduce motor functionality. Functional electrical stimulation is a technique that helps regain motor function, assisting patients in daily life activities and in rehabilitation practices. In this study, we evaluated the efficacy of a treatment based on whole-body Adaptive Functional Electrical Stimulation Kinesitherapy (AFESK (TM)) with the use of muscle synergies, a well-established method for evaluation of motor coordination. The evaluation is performed on retrospectively gathered data of neurological patients executing whole-body movements before and after AFESK-based treatments. Methods: Twenty-four chronic neurologic patients and 9 healthy subjects were recruited in this study. The patient group was further subdivided in 3 subgroups: hemiplegic, tetraplegic and paraplegic. All patients underwent two acquisition sessions: before treatment and after a FES based rehabilitation treatment at the VIKTOR Physio Lab. Patients followed whole-body exercise protocols tailored to their needs. The control group of healthy subjects performed all movements in a single session and provided reference data for evaluating patients' performance. sEMG was recorded on relevant muscles and muscle synergies were extracted for each patient's EMG data and then compared to the ones extracted from the healthy volunteers. To evaluate the effect of the treatment, the motricity index was measured and patients' extracted synergies were compared to the control group before and after treatment. Results: After the treatment, patients' motricity index increased for many of the screened body segments. Muscle synergies were more similar to those of healthy people. Globally, the normalized synergy similarity in respect to the control group was 0.50 before the treatment and 0.60 after (p < 0.001), with improvements for each subgroup of patients. Conclusions: AFESK treatment induced favorable changes in muscle activation patterns

关键词： Neurological disorders   CRISPR-Cas   Genome editing   Gene therapy  

摘要： Neurological disorders are primarily diseases with sophisticated etiology that are always refractory and recrudescent. The major obstruction to effective therapies for neurological disorders is the poor understanding of their pathogenic mechanisms. CRISPR-Cas9 technology, which allows precise and effective gene editing in almost any cell type and organism, is accelerating the pace of basic biological research. An increasing number of groups are focusing on uncovering the molecular mechanisms of neurological disorders and developing novel therapies using the CRISPR-Cas9 system. This review highlights the application of CRISPR-Cas9 technology in the treatment of neurological disorders, including Alzheimer's disease, amyotrophic lateral sclerosis and/or frontotemporal dementia, Duchenne muscular dystrophy, Dravet syndrome, epilepsy, Huntington's disease, and Parkinson's disease. Hopefully, it will improve our understanding of neurological disorders and give insights into future treatments for neurological disorders.

关键词： COVID-19   Long-COVID   Autonomic dysfunction   COMPASS-31   Orthostatic intolerance  

摘要： The autonomic nervous system (ANS) can be affected by COVID-19, and dysautonomia may be a possible complication in post-COVID individuals. Orthostatic hypotension (OH) and postural tachycardia syndrome (POTS) have been suggested to be common after SARS-CoV-2 infection, but other components of ANS function may be also impaired. The Composite Autonomic Symptom Scale 31 (COMPASS-31) questionnaire is a simple and validated tool to assess dysautonomic symptoms. The aim of the present study was to administer the COMPASS-31 questionnaire to a sample of post-COVID patients with and without neurological complaints. Participants were recruited among the post-COVID ambulatory services for follow-up evaluation between 4 weeks and 9 months from COVID-19 symptoms onset. Participants were asked to complete the COMPASS-31 questionnaire referring to the period after COVID-19 disease. Heart rate and blood pressure were manually taken during an active stand test for OH and POTS diagnosis. One-hundred and eighty participants were included in the analysis (70.6% females, 51 +/- 13 years), and OH was found in 13.8% of the subjects. Median COMPASS-31 score was 17.6 (6.9-31.4), with the most affected domains being orthostatic intolerance, sudomotor, gastrointestinal and pupillomotor dysfunction. A higher COMPASS-31 score was found in those with neurological symptoms (p < 0.01), due to more severe orthostatic intolerance symptoms (p < 0.01), although gastrointestinal (p < 0.01), urinary (p < 0.01), and pupillomotor (p < 0.01) domains were more represented in the non-neurological symptoms group. This study confirms the importance of monitoring ANS symptoms as a possible complication of COVID-19 disease that may persist in the post-acute period.