关键词： hydrogen gas therapy   subarachnoid hemorrhage   mortality   survival   early brain injury   high dose hydrogen   oxidative stress   free radicals   reactive oxygen species   hydrogen pathway   cerebral vasospasm  

摘要： The high morbidity, high mortality, and significant shortage of effective therapies for subarachnoid hemorrhage (SAH) have created an urgency to discover novel therapies. Human studies in Asia have established the safety of hydrogen gas in the treatment of hepatic, renal, pulmonary, and cardiac diseases. Mechanistically, hydrogen gas has been shown to affect oxidative stress, inflammation, and apoptosis. We hypothesized that hydrogen therapy would improve neurological function and increase survival rate in SAH. High dose hydrogen gas (66% at 3 L/min) was administered for 2 hours at 0.5, 8, and 18 hours after SAH. This treatment increased 72-hour survival rate and provided 24-hour neuroprotection after SAH in rats. To our knowledge, this is the first report demonstrating that high dose hydrogen gas therapy reduces mortality and improves outcome after SAH. Our results correlate well with the proposed mechanisms of hydrogen gas therapy within the literature. We outline four pathways and downstream targets of hydrogen gas potentially responsible for our results. A potentially complex network of pathways responsible for the efficacy of hydrogen gas therapy, along with a limited mechanistic understanding of these pathways, justifies further investigation to provide a basis for clinical trials and the advancement of hydrogen gas therapy in humans. This study was approved by the Institutional Animal Care and Use Committee of Loma Linda University, USA (Approval No. 8160016) in May 2016.

关键词： Body temperature   carbon monoxide   hyperthermia   poisoning   sequelae  

摘要： This study investigated whether hyperthermia within the first 24 h after presentation was associated with long-term neurological outcomes after acute carbon monoxide (CO) poisoning. This retrospective study included 200 patients with acute severe CO poisoning. Hyperthermia (>= 37.5 degrees C) developed during the first 24 h after presentation in 55 (27.5%) patients, and poor long-term neurological sequelae assessed at 23 months after acute CO poisoning developed in 19.5% of the patients. The incidence of poor long-term neurological outcomes was significantly higher in the hyperthermia group than in the normothermia group. Patients with poor long-term neurological outcomes had higher maximum temperatures than patients with good outcomes. No significant difference was found in the time of hyperthermia onset within the first day according to the neurological outcomes. Hyperthermia (adjusted odds ratio (aOR) 5.009 (95% confidence interval (CI) 1.556-16.126)) and maximum temperature (aOR 2.581 (95% CI 1.098-6.063)) within the first 24 h after presentation to the emergency department were independently associated with poor long-term neurological outcomes. Body temperature measurements, which are easily and noninvasively recorded at the bedside in any facility, help to predict the risk for poor long-term neurological outcomes. This study carefully emphasizes fastidious control of pyrexia, particularly during the early period after acute CO poisoning.

关键词： Motor neuron disease   Amyotrophic lateral sclerosis   Flail-leg syndrome   Flail-arm syndrome   FOSMN   FEWDON-MND  

摘要： Motor neuron disease (MND) represents a wide and heterogeneous expanding group of disorders involving the upper or lower motor neurons, mainly represented by amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy. Primary motor neuronopathies are characterized by progressive degenerative loss of anterior horn cell motoneurons (lower motor neurons) or loss of giant pyramidal Betz cells (upper motor neurons). Despite its well-known natural history, pathophysiological and clinical characteristics for the most common MND, atypical clinical presentation and neurodegenerative mechanisms are commonly observed in rare clinical entities, so-called atypical variants of MND-ALS, including flail-leg syndrome, flail-arm syndrome, facial-onset sensory and motor neuronopathy (FOSMN), finger extension weakness and downbeat nystagmus (FEWDON-MND) and long-lasting and juvenile MND-ALS. Herein, we provide a review article presenting clinical, genetic, pathophysiological and neuroimaging findings of atypical variants of MND-ALS in clinical practice. (C) 2019 Elsevier Masson SAS. All rights reserved.

关键词： Parental well-being   Rett syndrome   SF-12   Intellectual disability   Genetic disorder   Longitudinal study  

摘要： Little longitudinal research has examined parental well-being in those with a child with specific genetic developmental disorder although the associated severe neurological impairments and multiple physical comorbidities likely place substantial burden of caregiving on the parent. We aimed to examine longitudinally the well-being of parents of individuals included in the Australian Rett Syndrome Database over the period from 2002 to 2011 using the Short Form 12 Health Survey. Residential remoteness, the child being a teenager at baseline, having frequent sleep disturbances or behavioural problems, and the type of MECP2 gene mutation were each associated with later poorer parental physical well-being scores. Being a single parent or on a low income was also associated with later poorer physical well-being, while the child having enteral feeding was associated with later poorer emotional well-being. Both the physical and emotional well-being of the parent improved if the child was living in out-of-home care. Our findings suggest that some opportunities do exist for clinicians to help optimise parental well-being. Being alert to the possibility and need for management of a child's sleep or emotional disturbance is important as is awareness of the additional likely parental burden as the child moves through adolescence into early adulthood and their need for additional support at that time. However, the findings also highlight the complex nature of parental well-being over time in parents of children with a severe neurological disorder and how they may be affected by a range of inter-related family and child factors.

关键词： Multi-hit   Critical period   Early life stress   Glia   Neurons   Neurological disorders  

摘要： Early life Stress is a worldwide concern linked with development of later life neurological disorders. Early developmental age is sensitive to many prominent environmental insults like malnourishment, immune inflammation, abuse, maternal separation, alcohol and drugs. Hence, an individual during an early age encounters more than one simultaneous stressor that leads to impairment of cognitive and behavioral abilities, a symptom common to most of the neurological disorders. Stressors like malnourishment and immune inflammation are common and encountered by a huge number of populations, contributing enormously to a damaged CNS and in most of the cases they act synergistically in dependency to each other, giving rise to the concept of multi-hit. Multi perinatal hit acts by mimicking the mechanism of ageing in CNS and increasing the risk for later life neurological disorders. Multi stress exposure is also responsible for disrupting the cellular homeostasis of the brain by inducing glial activation, neurotoxicity and oxidative stress, which is the major reason of cell death and circuitry damage in brain. Multi perinatal hit thus increases the risk of neurological disorders by many folds through interfering with ongoing developmental cascades and eventually modulating the fate of cellular components in brain. Thus, a stress induced architecturally and chemically altered CNS is vulnerable and prone to neurological disorders like Alzheimer's, Schizophrenia, ALS, Autism and Parkinson's disease. This review compiles the information available regarding the effects of early life stressors on different components of brain, primarily focusing on the connection between perinatally encountered multi hit and development of later life neurological disorders.

关键词： Functional neurological disorders   Symptom count   Screening questionnaire   Neurological symptoms   Neuropsychiatry  

摘要： Objective: Diagnostic screening for functional neurological disorders (FNDs) continues to pose a challenge. Simple symptom counts fail clearly to discriminate patients with FND but there is increasing recognition of 'positive' features which are useful diagnostically during face-to-face assessments. A self-completed questionnaire evaluating specific features of FNDs would be useful for screening purposes in clinical and research settings. Methods: The Edinburgh Neurosymptoms Questionnaire (ENS) is a 30-item survey of presence and nature of: blackouts, weakness, hemisensory syndrome, memory problems, tremor, pain, fatigue, globus, multiple medical problems, and operations constructed via literature review and expert consensus. We conducted a pilot of the ENS on new general neurology clinic attendees at a large regional neuroscience centre. Patients were grouped according to consultant neurologist impression as having symptoms that were 'Not at all', 'Somewhat', 'Largely' or 'Completely' due to a functional disorder. Results: Blackouts, weakness and memory questions provided reasonable diagnostic utility (AUROC = 0.94, 0.71, 0.74 respectively) in single symptom analysis. All other symptoms lacked discriminating features. A multivariate linear model with all symptoms predicted functional classification with moderate diagnostic utility (AUROC = 0.83), specificity of 0.97, sensitivity of 0.47. Pain and blackout scores provided the most accurate predictor of functional classification. Conclusion. The ENS questionnaire provides some utility in differentiating patients presenting with functional blackouts but failed to provide diagnostic value in other types of FND, highlighting the limitations of this self report tool.

关键词： Blastocyst complementation   Chimera   Stem cells   Cell transplantation   Cognition   Behavior  

摘要： Blastocyst complementation is an emerging methodology in which human stem cells are transferred into genetically engineered preimplantation animal embryos eventually giving rise to fully developed human tissues and organs within the animal host for use in regenerative medicine. The ethical issues surrounding this method have caused the National Institutes of Health to issue a moratorium on funding for blastocyst complementation citing the potential for human cells to substantially contribute to the brain of the chimeric animal. To address this concern, we performed an in-depth review of the neural transplantation literature to determine how the integration of human cells into the nonhuman neural circuitry has altered the behavior of the host. Despite reports of widespread integration of human cell transplants, our review of 150 transplantation studies found no evidence suggestive of humanization of the animal host, and we thus conclude that, at present, concerns over humanization should not prevent research on blastocyst complementation to continue. We suggest proceeding in a controlled and transparent manner, however, and include recommendations for future research with careful consideration for how human cells may contribute to the animal host nervous system. Stem Cells2019;37:444-452

关键词： CARDIOGENIC shock   EXTRACORPOREAL membrane oxygenation  

摘要： Purpose Neurological complications (NC) are potentially devastating for cardiogenic shock patients receiving veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. The purpose of this study was to investigate the overall incidence and pattern of NC and their impact on *** We retrospectively reviewed 498 consecutive patients who received VA-ECMO support for cardiogenic shock between March 2007 and May 2018. Information on NC type, including stroke, altered mental status, seizure, encephalopathy, and transient ischemic attack and other neurological events was collected. Survival to discharge was compared between patients with and without neurological *** Median age of the entire cohort was 60 years (IQR 49-68), and 69% were male. Etiology of cardiogenic shock included post-cardiotomy shock (n=154, 33%), acute myocardial infarction (n=124, 27%), post-transplant graft failure (n=60, 13%), acute decompensated heart failure (n=65, 14%), and others (n=57, 12%). Eighty-seven patients were cannulated via the ascending aorta (18%), 37 via the axillary artery (7%), and 374 (75%) via the femoral artery. In total, 125 patients (25%) were diagnosed with NC: altered mental status was most common n=62 (12%), stroke n=29 (6%), encephalopathy n=16 (3%), seizure n=15 (3%), transient ischemic attack/others n=16 (3%). NC diagnosis was significantly associated with higher in-hospital mortality rates (74%, n=93) vs. non-NC diagnosis (61%, n=229), (p=0.008). Among NC subtypes, encephalopathy had the highest in-hospital mortality rate (94%, n=15), followed by stroke (72%, n=21) and AMS (71%, n=44).Conclusion Neurological disorders are common in cardiogenic shock patients who receive VA-ECMO and significantly impact in-hospital mortality rates.

关键词： avian bornavirus   neurological signs   feather-damaging behaviour  

摘要： Parrot bornaviruses (PaBV) are the causative agents of proventricular dilatation disease in psittacine birds, but have also been linked to other clinical signs, including behavioural disorders and neurological signs. The aim of this study was to correlate PaBV infection in birds showing feather-damaging behaviour or neurological signs for which no other cause of disease could be identified. Psittacine birds presented to a private practice were divided into three groups: birds with neurological signs (n = 28), birds showing feather-damaging behaviour (n = 42) and birds presented for routine examinations (n = 56). Swabs of crop and cloaca were collected and investigated for the presence of PaBV-RNA using real time RT-PCR. Additionally, serum samples were taken and examined for the presence of anti-PaBV antibodies by immunofluorescence test. PaBV infection was detected in one of the test systems in 40.5 per cent of all birds (n = 126) investigated. In the clinically healthy birds (n = 56), 19.6 per cent of the birds were positive in at least one of the PaBV tests, compared with 52.38 per cent of the feather-damaging (n = 42) and 64.28 per cent of the neurologically diseased birds (n = 28). Interestingly, the anti-PaBV antibody titres in birds with neurological signs were highest up to 1: 20480. High antibody titres (up to 1: 5120) were also found in the feather-damaging group, whereas the birds of the control group, if PaBV positive, had only very low titres. Similarly, the highest viral load was found in the group of the neurologically diseased birds, followed by feather-damaging birds, whereas PaBV-positive birds in the control group demonstrated only low viral RNA shedding. A clear correlation between severity of clinical signs, amount of viral shedding and high levels of antibody titres was observed for most of the neurologically diseased birds and also for few birds with feather-damaging behaviour. For the first time, these results clearly indicate a correlation b

关键词： PEG-600   Imidacloprid   Histopathology   Neuroalterations   Neurotransmitters Japanese quails  

摘要： Agrochemical risk assessment that takes into account only pesticide active ingredients without the spray adjuvants will miss important toxicity outcomes detrimental to non-target species including birds. In the present study toxicity of imidacloprid (IMI) pesticide was evaluated individually and in a mixture with polyethylene glycol (PEG-600) as adjuvant against Japanese quails. Oral intubation was used to obtain concentration-mortality data. Oral intubation was used to obtain concentration-mortality data. Treatments of quails for 24h with different doses leading to the calculation of LC50 values. PEG enhances the pesticide efficacy and the LD50 value of IMI was 17.02mg/Kg(1), and in combination with PEG it was 15.98mg/kg(-1). In the second phase of the study, the effects of a single acute dose of IMI (1/4 LD50) individually or in a mixture with PEG has a potent effect on the activity of plasma AChE and brain monoamines transmitters. However, the addition of PEG-adjuvant to the selected insecticide has shown more toxic potential, more highly significant decreases in AChE activity and different changes in cortical monoamines concentration. In the present study the maximum significant inhibition of AChE activity, was recorded post 72h exposure to IMI individually and 96h in a mixture with PEG and exhibited -37.56% and -32.65% decreases, respectively. Moreover, the oral intubation of IMI individually or in a mixture with PEG caused a significant elevation in the quail cortical NE and 5-HT. The result also showed while the mixture of IMI+PEG induced the more potent effect in DA alterations, IMI individually was more effective in 5-HT changes. Our findings also indicated that PEG exposure induced remarkable changes in the studied monoamines level and the values were significant throughout the tested periods in DA. Moreover, the studied dose level was vigorously affected quail brain cerebral cortex histological structure. When administered individually or in a mixture wit