关键词： Neurological   Aetiology   Electro-Magnetic-Fields   Environmental epigenetic  

摘要： Whilst humans evolved in the earth's Electro-Magnetic-Field (EMF) and sun-light, both being essential to life but too much sun and we burn. What happens if background EMF rise to critical levels, coinciding with increasing environmental pollutants? Two of the authors can look back over 50 clinical years and appreciate the profound changes in human morbidity across a range of disparate conditions autoimmune diseases, asthma, earlier cancer incidence and reduced male sperm counts. In particular have been increased autism, dyslexia, Attention Deficit Hyperactivity Disorder and neurological diseases, such as Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Parkinson's Disease, Early Onset Dementia, Multiple System Atrophy and Progressive Supranuclear Palsy. What might have caused these changes-whilst genetic factors are taken as given, multiple environmental pollutants are associated with neurological disease although the mechanisms are unclear. The pace of increased neurological deaths far exceeds any Gompertzian explanation - that because people are living longer they are more likely to develop more age-related problems such as neurological disease. Using WHO global mortality categories of Neurological Disease Deaths (NDD) and Alzheimer's and Dementia deaths (Alz), updated June 2018, together they constitute Total Neurological Mortality (TNM), to calculate mortality rates per million for people aged 55-74 and for the over-75's in twenty-one Western countries. Recent increases in American people aged over-75's rose 49% from 1989 to 2015 but US neurological deaths increased five-fold. In 1989 based on Age-Standardised-Deaths-Rates America USA was 17th at 324 pm but rising to 539 pm became second highest. Different environmental/occupational factors have been found to be associated with neuro-degenerative diseases, including background EMF. We briefly explore how levels of EMF interact upon the human body, which can be described as a natural antennae and provide new ev

关键词： Calreticulin   endoplasmic reticulum   proteostasis   phagocytosis   neurological disorder  

摘要： Calreticulin (CALR), a lectin-like ER chaperone, was initially known only for its housekeeping function, but today it is recognized for many versatile roles in different compartments of a cell. Apart from canonical roles in protein folding and calcium homeostasis, it performs a variety of noncanonical roles, mostly in CNS development. In the past, studies have linked Calreticulin with various other biological components which are detrimental in deciding the fate of neurons. Many neurological disorders that differ in their etiology are commonly associated with aberrant levels of Calreticulin, that lead to modulation of apoptosis and phagocytosis, and impact on transcriptional pathways, impairment in proteostatis, and calcium imbalances. Such multifaceted properties of Calreticulin are the reason why it has been implicated in vital roles of the nervous system in recent years. Hence, understanding its role in the physiology of neurons would help to unearth its involvement in the spectrum of neurological disorders. This Review aims toward exploring the interplay of Calreticulin in neurological disorders which would aid in targeting Calreticulin for developing novel neurotherapeutics.

摘要： Plain language summary Heart problems are common in newborn babies, affecting approximately 5-10 in 1000 babies. Some are more serious than others, but most babies born with heart problems do not have other health issues. Of those babies who have a serious heart problem, almost 1 in 4 will have heart surgery in their first year. In the UK, pregnant women are offered a scan at around 20 weeks to try and spot any heart problems. In most cases there is not a clear reason for the problem, but sometimes other issues, such as genetic conditions, are discovered. In recent years the care given to these babies after they are born has improved their chances of surviving. However, it is recognised that babies born with heart problems have a risk of delays in their learning and development. This may be due to their medical condition, or as a result of surgery and complications after birth. In babies with heart problems, there is a need for more research on ultrasound and magnetic resonance imaging (MRI) to understand how the brain develops and why these babies are more likely to have delays in learning and development. This paper discusses the way ultrasound and MRI are used in assessing the baby's brain. Ultrasound is often used to spot any problems, looking at how the baby's brain develops in pregnancy. Advances in ultrasound technologies have made this easier. MRI is well-established and safe in pregnancy, and if problems in the brain have been seen on ultrasound, MRI may be used to look at these problems in more detail. While it is not always clear what unusual MRI findings can mean for the baby in the long term, increased understanding may mean parents can be given more information about possible outcomes for the baby and may help to improve the counselling they are offered before their baby's birth.

关键词： Hypermmonemia   Cerebral herniation   Intracranial hypertension  

摘要： Highlights from the article: Hyperammonemia is a known cause of cerebral edema through multiple mechanistic pathways that ultimately converge on intracellular edema and toxic neuronal dysfunction [[1]-[3]]. While the presence of cerebral herniation has been reported to carry an overall unpropitious neurological prognosis, even with appropriate management, we present a case of severe hyperammonemia with cerebral edema and herniation where rapid and aggressive medical therapy resulted in complete neurological recovery, both clinically and radiographically [[9]]. The sulcal effacement, loss of ventricular size, and bilateral medialization of the uncus indicative of impeding herniation, secondary to cerebral edema in the initial scan (a) are completely reversed after successful treatment of the patient's elevated intracranial pressure and hyperammonemia (b) Furthermore, CVVHD is a rapid and safe bridging measure to effectively control hyperammonemia, and it should be initiated early and preferred in cases refractory to medical treatment with brain edema.

关键词： LENNOX-Gastaut syndrome   NEUROLOGICAL disorders   EPILEPSY   HUNTINGTON'S chorea   MECHANISM of action (Biochemistry)   ATTENTION-deficit hyperactivity disorder   MULTIPLE sclerosis  

摘要： SummaryIn the past two decades, there has been an increasing interest in the therapeutic potential of cannabinoids for neurological disorders such as epilepsy, multiple sclerosis, pain, and neurodegenerative diseases. Cannabis-based treatments for pain and spasticity in patients with multiple sclerosis have been approved in some countries. Randomised controlled trials of plant-derived cannabidiol for treatment of Lennox-Gastaut syndrome and Dravet syndrome, two severe childhood-onset epilepsies, provide evidence of anti-seizure effects. However, small clinical trials of cannabinoids in other neurological disorders such as Huntington’s disease, attention deficit hyperactivity disorder, and dementia, have not found any effect. Despite positive results in these two severe epilepsy syndromes, further studies are needed to determine if the anti-seizure effects of cannabidiol extend to other forms of epilepsy, to overcome pharmacokinetic challenges with oral cannabinoids, and to uncover the exact mechanisms by which cannabidiol or other exogenous and endogenous cannabinoids exert their therapeutic effects.

关键词： CEREBRAL palsy   HUMAN embryos   CORPUS callosum   CEREBRAL atrophy   ADAPTOR proteins  

摘要： c-Jun-amino-terminal kinase-interacting protein 3 (JIP3), encoded by MAPK8IP3, is an adaptor protein of the kinesin-1 complex and essential for axonal transport in neurons. However, an association between MAPK8IP3 variants and human disease has not been established. We identified 5 individuals from four families with recurrent de novo variants c.1732C>T (***578Cys) and c.3436C>T (***1146Cys) in MAPK8IP3. The core phenotype includes spastic diplegia, intellectual disability, cerebral atrophy, and corpus callosum hypoplasia. Zebrafish embryos overexpressing human mutant JIP3 showed axon varicosities of the posterior lateral line nerve, suggesting an adverse effect on the developing axons. Our results suggest that MAPK8IP3 variants cause a neurodevelopmental disease. ANN NEUROL 2019;85:927-933.

摘要： This commentary is on the original article by Oh et al. on pages 661-666 of this issue.

关键词： Cervical spondylotic myelopathy   Decompression   Prognosis   Surgical decompression  

摘要： Study Design: Prospective clinical study. Purpose: The present study aimed to examine the neurological recovery pattern in cervical spondylotic myelopathy ((CSM) CSM) after anterior cervical decompression and compare it with the existing reports in the literature. Overview of Literature: Neurological recovery and regression of myelopathy symptoms is an important factor that determines the outcomes of surgical decompression. The present findings contribute to the literature on the pattern of neurological recovery and patient prognosis with respect to the resolution of myelopathy symptoms after surgery. Methods: This prospective study was conducted in Government Medical College in Jammu, North India between November 2012 and October 2014, a total of 30 consecutive patients with CSM were included and treated with anterior decompression and stabilization. They were prospectively followed up for 1 year and were evaluated for their neurological recovery pattern. The postoperative outcome was evaluated using the modified Japanese Orthopaedic Association (mJOA) score. The recovery rate was calculated using Hirabayashi's method. The JOA score was assessed before the operation and postoperatively at 1 week, 2 weeks, 1 month, 3 months, 4 months, 6 months, and 1 year. Results: The postoperative mJOA score was 0 in the 1st month, 12.90 +/- 3.57 in the 3rd month, 13.50 +/- 3.55 in the 4th month, 14.63 +/- 3.62 in the 6th month, and 14.9 +/- 3.24 at the final follow-up of 1 year. The average recovery rate during the 1st month follow-up was 0%, and that during the 3rd month follow-up was 12.91% with a range of 0%-50%. The average recovery rate during the 4th month was 32.5%, with a range of 0%-60%, while that during the 6th month was 72.83%, with a range of 0%-100%. The average recovery rate during the final follow-up of 1 year was 54.3%. Conclusions: Neurological recovery after surgical decompression starts from the 3rd postoperative month and progresses until the 6th postoperativ

关键词： AMPK pathway   Chronic renal failure   Brain inflammation   Neurological function factor  

摘要： To explore the correlations between AMP-activated protein kinase (AMPK) expression and brain inflammatory response and neurological function factors in rats with chronic renal failure. Chronic renal failure models in rats were established, and the healthy control group (normal group) was set. Chronic renal failure model rats were divided into model group (without any treatment), control group (intraperitoneal injection of normal saline), A-769662 group (intraperitoneal injection of AMPK specific activator), and compound C group (intraperitoneal injection of AMPK specific inhibitor). The results of HE staining showed renal tissue enlargement, and significant pathological changes. Compared with the normal group, AMPK level in peripheral blood and AMPK mRNA and protein expressions in brain tissue were significantly reduced, and AMPK pathway activation was significantly inhibited in other groups. Compared with the model group, rats in the A-769662 group had significantly decreased serum creatinine (Scr) and blood urea nitrogen (BUN) levels and -aminobutyric acid (-GABA) content, significantly increased brain-derived neurotrophic factor (BDNF) positive expressions and 5-hydroxytryptamine (5-HT) content, and decreased interleukin-1 (IL-1), tumor necrosis factor- (TNF-), and intercellular adhesion molecule 1 (ICAM-1) expressions (all P<0.05), while it was just the opposite in compound C group (all P<0.05). There is an apparent correlation between AMPK expression and brain inflammatory response in chronic renal failure rats. AMPK is expected to be an important pathway in the treatment of uremic encephalopathy.

关键词： Autonomic dysfunction   Neurological intensive care medicine   Guillain-Barre-syndrome   Tetanus   Botulism   Alcohol withdrawal syndrome   Paroxysmal sympathetic hyperactivity  

摘要： Autonomic dysfunction is common in neuro-critical care patients and may compromise the function of various organs. Among the many diseases causing or being associated with autonomic dysfunction are traumatic brain injury, cerebrovascular diseases, epilepsy, Guillain-Barre syndrome (GBS), alcohol withdrawal syndrome, botulism and tetanus, among many others. Autonomic dysfunction may afflict various organs and may involve hyper-or hypo-activity of the sympathetic or parasympathetic system. In this short overview, we address only a small number of neuro-intensive care diseases with autonomic dysfunction. In GBS, autonomic dysfunction is frequent and may account for increased mortality rates;rapid changes between sympathetic and parasympathetic hypo-or hyper-activity may cause life-threatening cardiovascular complications. Paroxysmal sympathetic hyperactivity occurs after brain injury, hypoxia and cerebrovascular and other events, causes paroxysmal tachycardia, hypertension, tachypnoea and hyperthermia and is associated with a poorer prognosis and prolonged intensive care treatment. Other, at times life-threatening autonomic complications with exaggerated sympathetic activity and compromised baroreflex sensitivity arise during the alcohol withdrawal syndrome triggered by abrupt cessation of alcohol consumption. Botulism and tetanus are examples of life-threatening autonomic dysfunction caused by bacterial neurotoxins. Common neurological diseases, such as epilepsy, stroke or subarachnoid haemorrhage, are also associated with autonomic dysfunction that can on occasion cause critical deterioration of disease severity and prognosis.