An invertebrate model for CNS drug discovery

DEFF Research Database (Denmark)

Al-Qadi, Sonia; Schiøtt, Morten; Hansen, Steen Honoré

2015-01-01

BACKGROUND: ABC efflux transporters at the blood brain barrier (BBB), namely the P-glycoprotein (P-gp), restrain the development of central nervous system (CNS) drugs. Consequently, early screening of CNS drug candidates is pivotal to identify those affected by efflux activity. Therefore, simple,...... barriers. CONCLUSION: Findings suggest a conserved mechanism of brain efflux activity between insects and vertebrates, confirming that this model holds promise for inexpensive and high-throughput screening relative to in vivo models, for CNS drug discovery....

Drug Delivery to CNS: Challenges and Opportunities with Emphasis on Biomaterials Based Drug Delivery Strategies.

Science.gov (United States)

Khambhla, Ekta; Shah, Viral; Baviskar, Kalpesh

2016-01-01

The current epoch has witnessed a lifestyle impregnated with stress, which is a major cause of several neurological disorders. High morbidity and mortality rate due to neurological diseases and disorders have generated a huge social impact. Despite voluminous research, patients suffering from fatal and/or debilitating CNS diseases such as brain tumors, HIV, encephalopathy, Alzheimer's, epilepsy, Parkinson's, migraine and multiple sclerosis outnumbered those suffering from systemic cancer or heart diseases. The brain being a highly sensitive neuronal organ, has evolved with vasculature barriers, which regulates the efflux and influx of substances to CNS. Treatment of CNS diseases/disorders is challenging because of physiologic, metabolic and biochemical obstacles created by these barriers which comprise mainly of BBB and BCFB. The inability of achieving therapeutically active concentration has become the bottleneck level difficulty, hampering the therapeutic efficiency of several promising drug candidates for CNS related disorders. Parallel maturation of an effective CNS drug delivery strategy with CNS drug discovery is the need of the hour. Recently, the focus of the pharmaceutical community has aggravated in the direction of developing novel and more efficient drug delivery systems, giving the potential of more effective and safer CNS therapies. The present review outlines several hurdles in drug delivery to the CNS along with ideal physicochemical properties desired in drug substance/formulation for CNS delivery. The review also focuses on different conventional and novel strategies for drug delivery to the CNS. The article also assesses and emphasizes on possible benefits of biomaterial based formulations for drug delivery to the CNS.

[Creatine kinase BB and lactate in the cerebrospinal fluid of neonates and infants with perinatal injuries of the CNS].

Science.gov (United States)

Alatyrtsev, V V; Iakunin, Iu A; Burkova, A S; Podkopaev, V N; Afonina, L G

1989-01-01

A study was made of the content of creatine kinase-BB (CK-BB) and lactate in cerebrospinal fluid (CSF) of 202 neonates and infants with perinatal CNS injuries. The relationship was found between the rise of the CK-BB content and the gravity of perinatal CNS injuries. The highest content of CK-BB in CSF was marked in neonates with cerebral disorders complicated by infectious and inflammatory diseases (pneumonia, sepsis). Within the first 5 days of life, the children of this group demonstrated the relationship between the content of CK-BB and lactate of CSF. The measurement of the content of CK-BB in CSF should be used for early diagnosis, assessment of the gravity and course of perinatal CNS injuries in neonates and in infants.

CNS-directed gene therapy for lysosomal storage diseases

OpenAIRE

Sands, Mark S; Haskins, Mark E

2008-01-01

Lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders usually caused by deficient activity of a single lysosomal enzyme. As most lysosomal enzymes are ubiquitously expressed, a deficiency in a single enzyme can affect multiple organ systems, including the central nervous system (CNS). At least 75% of all LSDs have a significant CNS component. Approaches such as bone marrow transplantation (BMT) or enzyme replacement therapy (ERT) can effectively treat the systemic dis...

Adverse CNS-effects of beta-adrenoceptor blockers.

Science.gov (United States)

Gleiter, C H; Deckert, J

1996-11-01

In 1962 propranolol, the first beta adrenoceptor antagonist (beta blocker), was brought on to the market. There is now a host of different beta blockers available, and these compounds are among the most commonly prescribed groups of drugs. The efficacy of beta blockers has been proven predominantly for the treatment of cardiovascular diseases. Beta blockers are also used for certain types of CNS disorders, such as anxiety disorders, essential tremor and migraine. While low toxicity means that they have a favorable risk-benefit ratio, given the high intensity of use, it is essential to have a comprehensive knowledge of adverse events. Adverse events of beta blockers that can be related to the CNS are quite often neglected, even in textbooks of clinical pharmacology or review articles, and thus often misdiagnosed. The following article, therefore, after summarizing the use of beta blockers for CNS indications, critically reviews the literature on centrally mediated adverse events. General pharmacological features of beta blockers and their molecular basis of action will briefly be addressed to the extent that they are or may become relevant for central nervous pharmacotherapy and side-effects.

Early Intervention in Bipolar Disorder.

Science.gov (United States)

Vieta, Eduard; Salagre, Estela; Grande, Iria; Carvalho, André F; Fernandes, Brisa S; Berk, Michael; Birmaher, Boris; Tohen, Mauricio; Suppes, Trisha

2018-05-01

Bipolar disorder is a recurrent disorder that affects more than 1% of the world population and usually has its onset during youth. Its chronic course is associated with high rates of morbidity and mortality, making bipolar disorder one of the main causes of disability among young and working-age people. The implementation of early intervention strategies may help to change the outcome of the illness and avert potentially irreversible harm to patients with bipolar disorder, as early phases may be more responsive to treatment and may need less aggressive therapies. Early intervention in bipolar disorder is gaining momentum. Current evidence emerging from longitudinal studies indicates that parental early-onset bipolar disorder is the most consistent risk factor for bipolar disorder. Longitudinal studies also indicate that a full-blown manic episode is often preceded by a variety of prodromal symptoms, particularly subsyndromal manic symptoms, therefore supporting the existence of an at-risk state in bipolar disorder that could be targeted through early intervention. There are also identifiable risk factors that influence the course of bipolar disorder, some of them potentially modifiable. Valid biomarkers or diagnosis tools to help clinicians identify individuals at high risk of conversion to bipolar disorder are still lacking, although there are some promising early results. Pending more solid evidence on the best treatment strategy in early phases of bipolar disorder, physicians should carefully weigh the risks and benefits of each intervention. Further studies will provide the evidence needed to finish shaping the concept of early intervention. AJP AT 175 Remembering Our Past As We Envision Our Future April 1925: Interpretations of Manic-Depressive Phases Earl Bond and G.E. Partridge reviewed a number of patients with manic-depressive illness in search of a unifying endo-psychic conflict. They concluded that understanding either phase of illness was "elusive" and

Ethnopharmacological study of medicinal plants used in the treatment of CNS disorders in Sinai Peninsula, Egypt.

Science.gov (United States)

Eissa, T A F; Palomino, O M; Carretero, M E; Gómez-Serranillos, M P

2014-01-01

To provide ethnopharmacological information on the use of medicinal plants for central nervous system (CNS) disorders in the Sinai Peninsula region (Egypt). To collect, analyze and evaluate the ethnobotanical knowledge about these medicinal plants in the Sinai Peninsula region with 61,000 km (2) and 379,000 inhabitants. Field work was concluded between March 2006 and May 2011, using semi-structured questionnaire with 700 informants (mean age: 59; 100% men) from 117 settlements of 17 Bedouin tribes. Transects walks in wild herbal plant collection areas and bibliographical review on the collected plants were also conducted. The Interview/ Inhabitant index (I/P), relative importance value of the species and informant consensus factor (FIC) were calculated. More than 300 species were traditionally used in folk medicine in the Sinai Peninsula; 101 of these species belonging to 40 families were reported as useful in different CNS disorders. Only 5 species are endemic of the studied area. All different part plants were used, leaves and aerial parts being the most frequent. Most of the remedies were prepared as infusion or decoction, while oral administration was the most common way to be used. Gastrointestinal (67.3%) and respiratory disorders (42.57%) were also reported as frequently treated by Bedouins with herbal remedies. Only a few species were found where the traditional use is supported by pharmacological studies (Acacia nilotica, Achillea fragrantissima, Ajuga iva or Mentha longifolia). No bibliographical references in the scientific literature were found for 22 species (21.78%); finally, several studies were published with different pharmacological activities than those provided by Bedouins. © 2013 The Authors. Published by Elsevier Ireland Ltd All rights reserved.

CNS penetration of intrathecal-lumbar idursulfase in the monkey, dog and mouse: implications for neurological outcomes of lysosomal storage disorder.

Directory of Open Access Journals (Sweden)

Pericles Calias

Full Text Available A major challenge for the treatment of many central nervous system (CNS disorders is the lack of convenient and effective methods for delivering biological agents to the brain. Mucopolysaccharidosis II (Hunter syndrome is a rare inherited lysosomal storage disorder resulting from a deficiency of iduronate-2-sulfatase (I2S. I2S is a large, highly glycosylated enzyme. Intravenous administration is not likely to be an effective therapy for disease-related neurological outcomes that require enzyme access to the brain cells, in particular neurons and oligodendrocytes. We demonstrate that intracerebroventricular and lumbar intrathecal administration of recombinant I2S in dogs and nonhuman primates resulted in widespread enzyme distribution in the brain parenchyma, including remarkable deposition in the lysosomes of both neurons and oligodendrocytes. Lumbar intrathecal administration also resulted in enzyme delivery to the spinal cord, whereas little enzyme was detected there after intraventricular administration. Mucopolysaccharidosis II model is available in mice. Lumbar administration of recombinant I2S to enzyme deficient animals reduced the storage of glycosaminoglycans in both superficial and deep brain tissues, with concurrent morphological improvements. The observed patterns of enzyme transport from cerebrospinal fluid to the CNS tissues and the resultant biological activity (a warrant further investigation of intrathecal delivery of I2S via lumbar catheter as an experimental treatment for the neurological symptoms of Hunter syndrome and (b may have broader implications for CNS treatment with biopharmaceuticals.

Targeting α4β2 nAChRs in CNS disorders: Perspectives on positive allosteric modulation as a therapeutic approach

DEFF Research Database (Denmark)

Grupe, Morten; Grunnet, Morten; Bastlund, Jesper F.

2015-01-01

The nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels broadly involved in regulating neurotransmission in the central nervous system (CNS) by conducting cation currents through the membrane of neurons. Many different nAChR subtypes exist with each their functional character......The nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels broadly involved in regulating neurotransmission in the central nervous system (CNS) by conducting cation currents through the membrane of neurons. Many different nAChR subtypes exist with each their functional...... characteristics, expression pattern and pharmacological profile. The focus of the present MiniReview is on the heteromeric α4β2 nAChR, as activity at this subtype contributes to cognitive functioning through interactions with multiple neurotransmitter systems and is implicated in various CNS disorders...... and temporal aspects of neurotransmission as well as higher subtype selectivity, hypothetically resulting in high clinical efficacy with minimal adverse effects. In this MiniReview, we describe the currently identified compounds, which potentiate the effects of agonists at the α4β2 nAChR. The potential...

EBI2 Is Highly Expressed in Multiple Sclerosis Lesions and Promotes Early CNS Migration of Encephalitogenic CD4 T Cells

Directory of Open Access Journals (Sweden)

Florian Wanke

2017-01-01

Full Text Available Arrival of encephalitogenic T cells at inflammatory foci represents a critical step in development of experimental autoimmune encephalomyelitis (EAE, the animal model for multiple sclerosis. EBI2 and its ligand, 7α,25-OHC, direct immune cell localization in secondary lymphoid organs. CH25H and CYP7B1 hydroxylate cholesterol to 7α,25-OHC. During EAE, we found increased expression of CH25H by microglia and CYP7B1 by CNS-infiltrating immune cells elevating the ligand concentration in the CNS. Two critical pro-inflammatory cytokines, interleukin-23 (IL-23 and interleukin-1 beta (IL-1β, maintained expression of EBI2 in differentiating Th17 cells. In line with this, EBI2 enhanced early migration of encephalitogenic T cells into the CNS in a transfer EAE model. Nonetheless, EBI2 was dispensable in active EAE. Human Th17 cells do also express EBI2, and EBI2 expressing cells are abundant within multiple sclerosis (MS white matter lesions. These findings implicate EBI2 as a mediator of CNS autoimmunity and describe mechanistically its contribution to the migration of autoreactive T cells into inflamed organs.

[Autism: An early neurodevelopmental disorder].

Science.gov (United States)

Bonnet-Brilhault, F

2017-04-01

With approximately 67 million individuals affected worldwide, autism spectrum disorder (ASD) is the fastest growing neurodevelopmental disorder (United Nations, 2011), with a prevalence estimated to be 1/100. In France ASD affects approximately 600,000 individuals (from childhood to adulthood, half of whom are also mentally retarded), who thus have a major handicap in communication and in adapting to daily life, which leads autism to be recognized as a national public health priority. ASD is a neurodevelopmental disorder that affects several domains (i.e., socio-emotional, language, sensori-motor, executive functioning). These disorders are expressed early in life with an age of onset around 18 months. Despite evidence suggesting a strong genetic link with ASD, the genetic determinant remains unclear. The clinical picture is characterized by impairments in social interaction and communication and the presence of restrictive and repetitive behaviors (DSM-5, ICD-10). However, in addition to these two main dimensions there is significant comorbidity between ASD and other neurodevelopmental disorders such as attention deficit hyperactivity disorder or with genetic and medical conditions. One of the diagnostic features of ASD is its early emergence: symptoms must begin in early childhood for a diagnosis to be given. Due to brain plasticity, early interventions are essential to facilitate clinical improvement. Therefore, general practitioners and pediatricians are on the front line to detect early signs of ASD and to guide both medical explorations and early rehabilitation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

When the Tail Can't Wag the Dog: The Implications of CNS-Intrinsic Initiation of Neuroinflammation

Directory of Open Access Journals (Sweden)

Deirdre S Davis

2009-04-01

Full Text Available The CNS (central nervous system is unquestionably the central organ that regulates directly or indirectly all physiological systems in the mammalian body. Yet, when considering the defence of the CNS from pathogens, the CNS has often been considered passive and subservient to the pro-inflammatory responses of the immune system. In this view, neuroinflammatory disorders are examples of when the tail (the immune system wags the dog (the CNS to the detriment of an individual's function and survival.

Early-onset obsessive-compulsive disorder and personality disorders in adulthood.

Science.gov (United States)

Maina, Giuseppe; Albert, Umberto; Salvi, Virginio; Pessina, Enrico; Bogetto, Filippo

2008-03-15

Obsessive-compulsive disorder (OCD) often emerges in childhood or adolescence. The aim of the present study was to evaluate whether adult patients with prepuberal onset differ from subjects with later onset in terms of personality disorder comorbidity. The Structured Clinical Interview for DSM-IV Axis II Disorders was used to assess 148 patients with a principal diagnosis of OCD according to the Structured Clinical Interview for DSM-IV Axis I Disorders. The following two subgroups of subjects were selected according to the age at onset of symptomatology: patients with an early-onset ( or =17 years). Of the 148 patients screened for the present study, 33 (22.3%) had an early onset and 1369 (46.6%) had a later onset. With regard to personality disorders, early-onset patients showed more OC personality disorders (OCPD) than later onset patients. Our finding suggests that OCD in childhood increases the risk for developing OCPD in adulthood, or that early-onset OCD and OCPD share a common pathogenesis.

CNS Involvement in Hemophagocytic Lymphohistiocytosis: CT and MR Findings

International Nuclear Information System (INIS)

Chung, Tae Woong

2007-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder that is characterized by proliferation of benign histiocytes, and this commonly involves the liver, spleen, lymph nodes, bone marrow and central nervous system (CNS). We report here on the CT and MR imaging findings in a case of CNS HLH that showed multiple ring enhancing masses mimicking abscess or another mass on the CT and MR imaging. emophagocytic lymphohistiocytosis (HLH) is a rare disorder that is characterized by nonmalignant diffuse infiltration of multiple organs, including the central nervous system (CNS), by lymphocytes and histiocytes (1). Many radiologic reports describing diffuse white matter infiltrations, parenchymal atrophy and calcification have been published, but the characteristics of these findings remain non-specific, especially in immunocompromised patients. We present here a case of HLH in a 3-year-old boy who presented with multiple ring enhancing lesions involving the brain. In conclusion, although the CT and MRI findings of HLH with ring enhancing parenchymal lesions are nonspecific and mimic abscess, and especially in the immunosuppressed patients, increased diffusion at the center on DWI may be a finding of HLH to differentiate it from abscess, which has restricted diffusion at the center. However, the pathologic correlation with DWI according to the lesion stage certainly needs further study with a larger number of patients

The MiRNA Journey from Theory to Practice as a CNS Biomarker

Directory of Open Access Journals (Sweden)

Nicoleta eStoicea

2016-02-01

Full Text Available MicroRNAs (miRNAs, small nucleotide sequences that control gene transcription, have the potential to serve an expanded function as indicators in the diagnosis and progression of neurological disorders. Studies involving debilitating neurological diseases such as, Alzheimer’s disease, multiple sclerosis, traumatic brain injuries, Parkinson’s disease and CNS tumors, already provide validation for their clinical diagnostic use. These small nucleotide sequences have several features, making them favorable candidates as biomarkers, including function in multiple tissues, stability in bodily fluids, a role in pathogenesis, and the ability to be detected early in the disease course. Cerebrospinal fluid, with its cell-free environment, collection process that minimizes tissue damage, and direct contact with the brain and spinal cord, is a promising source of miRNA in the diagnosis of many neurological disorders. Despite the advantages of miRNA analysis, current analytic technology is not yet affordable as a clinically viable diagnostic tool and requires standardization. The goal of this review is to explore the prospective use of CSF miRNA as a reliable and affordable biomarker for different neurological disorders.

The MiRNA Journey from Theory to Practice as a CNS Biomarker

Science.gov (United States)

Stoicea, Nicoleta; Du, Amy; Lakis, D. Christie; Tipton, Courtney; Arias-Morales, Carlos E.; Bergese, Sergio D.

2016-01-01

MicroRNAs (miRNAs), small nucleotide sequences that control gene transcription, have the potential to serve an expanded function as indicators in the diagnosis and progression of neurological disorders. Studies involving debilitating neurological diseases such as, Alzheimer's disease, multiple sclerosis, traumatic brain injuries, Parkinson's disease and CNS tumors, already provide validation for their clinical diagnostic use. These small nucleotide sequences have several features, making them favorable candidates as biomarkers, including function in multiple tissues, stability in bodily fluids, a role in pathogenesis, and the ability to be detected early in the disease course. Cerebrospinal fluid, with its cell-free environment, collection process that minimizes tissue damage, and direct contact with the brain and spinal cord, is a promising source of miRNA in the diagnosis of many neurological disorders. Despite the advantages of miRNA analysis, current analytic technology is not yet affordable as a clinically viable diagnostic tool and requires standardization. The goal of this review is to explore the prospective use of CSF miRNA as a reliable and affordable biomarker for different neurological disorders. PMID:26904099

Management of mental health disorders and central nervous system sequelae in HIV-positive children and adolescents

Directory of Open Access Journals (Sweden)

R Nassen

2014-09-01

Full Text Available HIV-positive children and adolescents are at increased risk of both central nervous system (CNS sequelae and mental disorders owing to a number of factors, including the impact of HIV infection on the brain, social determinants of health (e.g. poverty and orphanhood and psychosocial stressors related to living with HIV. Every effort should be made to identify perinatally HIV-infected children and initiate them on antiretroviral therapy early in life. HIV clinicians should ideally screen for mental health and neurocognitive problems, as part of the routine monitoring of children attending antiretroviral clinics. This guideline is intended as a reference tool for HIV clinicians to support the early identification, screening and management of mental health disorders and/or CNS impairment in children and adolescents. This guideline covers mental disorders (section 1 and HIV-associated neurocognitive disorders (section 2 among children and adolescents.

Ultra-sensitive molecular MRI of cerebrovascular cell activation enables early detection of chronic central nervous system disorders

International Nuclear Information System (INIS)

Montagne, Axel; Gauberti, Maxime; Jullienne, Amandine; Briens, Aurelien; Docagne, Fabian; Vivien, Denis; Maubert, Eric; Macrez, Richard; Defer, Gilles; Raynaud, Jean-Sebastien; Louin, Gaelle; Buisson, Alain; Haelewyn, Benoit

2012-01-01

Since endothelial cells can be targeted by large contrast-carrying particles, molecular imaging of cerebrovascular cell activation is highly promising to evaluate the underlying inflammation of the central nervous system (CNS). In this study, we aimed to demonstrate that molecular magnetic resonance imaging (MRI) of cerebrovascular cell activation can reveal CNS disorders in the absence of visible lesions and symptoms. To this aim, we optimized contrast carrying particles targeting vascular cell adhesion molecule-1 and MRI protocols through both in vitro and in vivo experiments. Although, pre-contrast MRI images failed to reveal the ongoing pathology, contrast-enhanced MRI revealed hypoperfusion-triggered CNS injury in vascular dementia, unmasked amyloid-induced cerebrovascular activation in Alzheimer's disease and allowed monitoring of disease activity during experimental autoimmune encephalomyelitis. Moreover, contrast-enhanced MRI revealed the cerebrovascular cell activation associated with known risk factors of CNS disorders such as peripheral inflammation, ethanol consumption, hyperglycemia and aging. By providing a dramatically higher sensitivity than previously reported methods and molecular contrast agents, the technology described in the present study opens new avenues of investigation in the field of neuro-inflammation. (authors)

CLIPPERS among patients diagnosed with non-specific CNS neuroinflammatory diseases

DEFF Research Database (Denmark)

Kerrn-Jespersen, B M; Lindelof, M; Illes, Zsolt

2014-01-01

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) is an inflammatory CNS disorder characterized by 1) subacute onset of cerebellar and brainstem symptoms, 2) peripontine contrast-enhancing perivascular lesions with a "salt-and-pepper" appeara...

Bipolar Disorder and Early Affective Trauma.

Science.gov (United States)

de Codt, Aloise; Monhonval, Pauline; Bongaerts, Xavier; Belkacemi, Ikram; Tecco, Juan Martin

2016-09-01

Bipolar disorder is a chronic psychiatric disease with a high prevalence and is a major psychosocial and medical burden. The exact etiological pathways of bipolar disorder are not fully understood. Genetic factors are known to play an important role in the etiology of bipolar disorder. However, high rates of discordance among identical twins and a growing body of evidence that environmental factors such as early stress can influence the onset and course of psychiatric diseases underline the importance of additional etiological mechanisms of bipolar disorders. There has been little investigation about early trauma in bipolar disorder. The aim of this study was to review the literature on the association between early traumatic interactions like child neglect, mistreatment, abuse or early parental separation and the occurrence of bipolar disorder in adulthood or impact on the course of the disease. Studies investigating associations between child neglect, mistreatment, abuse or early parental separation and occurrence of bipolar disorder in adulthood or impact on the course of the disease were searched in the Pubmed database. More than 700 articles were sorted independently by two of the authors using predefined criteria. Only research articles, reviews and meta-analyses were selected for this review. 53 articles met the inclusion criteria. To date, four systematic reviews partially addressed our research question. Early trauma is more frequently found in the past of bipolar patients than in the general population. Studies support a harmful effect of childhood trauma on the course of bipolar disease, with more anxious, depressive or psychotic symptoms, an early age of onset and a worse prognosis. Early trauma is more often found in the past of bipolar adult patients than the general population and studies support a harmful effect of childhood trauma on the course of bipolar disease, with more anxious, depressive or psychotic symptoms, an early age of onset and a

Behavioral and Genetic Evidence for GIRK Channels in the CNS: Role in Physiology, Pathophysiology, and Drug Addiction.

Science.gov (United States)

Mayfield, Jody; Blednov, Yuri A; Harris, R Adron

2015-01-01

G protein-coupled inwardly rectifying potassium (GIRK) channels are widely expressed throughout the brain and mediate the inhibitory effects of many neurotransmitters. As a result, these channels are important for normal CNS function and have also been implicated in Down syndrome, Parkinson's disease, psychiatric disorders, epilepsy, and drug addiction. Knockout mouse models have provided extensive insight into the significance of GIRK channels under these conditions. This review examines the behavioral and genetic evidence from animal models and genetic association studies in humans linking GIRK channels with CNS disorders. We further explore the possibility that subunit-selective modulators and other advanced research tools will be instrumental in establishing the role of individual GIRK subunits in drug addiction and other relevant CNS diseases and in potentially advancing treatment options for these disorders. © 2015 Elsevier Inc. All rights reserved.

Neuropeptide Y in Alcohol Addiction and Affective Disorders

Directory of Open Access Journals (Sweden)

Annika Thorsell

2017-07-01

Full Text Available Neuropeptide Y (NPY, a neuropeptide highly conserved throughout evolution, is present at high levels in the central nervous system (CNS, as well as in peripheral tissues such as the gut and cardiovascular system. The peptide exerts its effects via multiple receptor subtypes, all belonging to the G-protein-coupled receptor superfamily. Of these subtypes, the Y1 and the Y2 are the most thoroughly characterized, followed by the Y5 subtype. NPY and its receptors have been shown to be of importance in central regulation of events underlying, for example, affective disorders, drug/alcohol use disorders, and energy homeostasis. Furthermore, within the CNS, NPY also affects sleep regulation and circadian rhythm, memory function, tissue growth, and plasticity. The potential roles of NPY in the etiology and pathophysiology of mood and anxiety disorders, as well as alcohol use disorders, have been extensively studied. This focus was prompted by early indications for an involvement of NPY in acute responses to stress, and, later, also data pointing to a role in alterations within the CNS during chronic, or repeated, exposure to adverse events. These functions of NPY, in addition to the peptide’s regulation of disease states, suggest that modulation of the activity of the NPY system via receptor agonists/antagonists may be a putative treatment mechanism in affective disorders as well as alcohol use disorders. In this review, we present an overview of findings with regard to the NPY system in relation to anxiety and stress, acute as well as chronic; furthermore we discuss post-traumatic stress disorder and, in part depression. In addition, we summarize findings on alcohol use disorders and related behaviors. Finally, we briefly touch upon genetic as well as epigenetic mechanisms that may be of importance for NPY function and regulation. In conclusion, we suggest that modulation of NPY-ergic activity within the CNS, via ligands aimed at different receptor

The mastermind approach to CNS drug therapy: translational prediction of human brain distribution, target site kinetics, and therapeutic effects

OpenAIRE

de Lange, Elizabeth CM

2013-01-01

Despite enormous advances in CNS research, CNS disorders remain the world?s leading cause of disability. This accounts for more hospitalizations and prolonged care than almost all other diseases combined, and indicates a high unmet need for good CNS drugs and drug therapies. Following dosing, not only the chemical properties of the drug and blood?brain barrier (BBB) transport, but also many other processes will ultimately determine brain target site kinetics and consequently the CNS effects. ...

CNS role evolution.

Science.gov (United States)

Payne, J L; Baumgartner, R G

1996-01-01

THE CNS ROLE has been actualized in a variety of ways. Flexibility-inherent in the role-and the revolution in health care consciousness tend to place the CNS at risk for criticism regarding value to the organization. At Vanderbilt University Medical Center, a CNS task force evaluated the current reality of CNS practice and recommended role changes to include the financial analysis of patient care. After incorporating a financial perspective into our present practice, we have embarked on an interesting journey of post-Master's degree study, that of the tertiary care nurse practitioner. This practice option could elevated the clinical and financial aspects of providing cost-effective health care to a more autonomous role form; however, the transition has been challenging. Since 1990, the American Nurses Association has recommended that nursing school curricula change to meet the needs of the health care environment and provide increased career flexibility through creating one advanced degree incorporating both CNS and NP functions. Swiftly moving past differences and toward similarities will bridge the gap for advanced practice nurses in the future.

Microtubule-Targeting Agents Enter the Central Nervous System (CNS): Double-edged Swords for Treating CNS Injury and Disease.

Science.gov (United States)

Hur, Eun-Mi; Lee, Byoung Dae

2014-12-01

Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs) are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS) are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

Microtubule-Targeting Agents Enter the Central Nervous System (CNS: Double-edged Swords for Treating CNS Injury and Disease

Directory of Open Access Journals (Sweden)

Eun-Mi Hur

2014-12-01

Full Text Available Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

Integrating Early Intervention for Borderline Personality Disorder and Mood Disorders.

Science.gov (United States)

Chanen, Andrew M; Berk, Michael; Thompson, Katherine

2016-01-01

Borderline personality disorder (BPD) has been demonstrated to be a reliable and valid construct in young people (adolescents and young adults). Both borderline- and mood-related psychopathology become clinically apparent from puberty through to young adulthood, frequently co-occur, can reinforce one another, and can be difficult to differentiate clinically. This Gordian knot of overlapping clinical features, common risk factors, and precursors to both BPD and mood disorders complicates clinical assessment, prevention, and treatment. Regardless of whether an individual crosses an arbitrary diagnostic threshold, a considerable proportion of young people with borderline- and mood-related psychopathology will develop significant and persistent functional, vocational, and interpersonal impairment and disability during this critical risk and developmental period. There is a clear need for early intervention, but spurious diagnostic certainty risks stigma, misapplication of diagnostic labels, inappropriate treatment, and unfavorable outcomes. This article aims to integrate early intervention for BPD and mood disorders in the clinical context of developmental and phenomenological change and evolution. "Clinical staging," similar to disease staging in general medicine, is presented as a pragmatic, heuristic, and trans-diagnostic framework to guide prevention and intervention. It acknowledges that the early stages of these disorders cannot be disentangled sufficiently to allow for disorder-specific preventive measures and early interventions. Clinical staging defines an individual's location along the continuum of the evolving temporal course of a disorder. Such staging aids differentiation of early or milder clinical phenomena from those that accompany illness progression and chronicity, and suggests the application of appropriate and proportionate intervention strategies.

Causes of CNS inflammation and potential targets for anticonvulsants.

Science.gov (United States)

Falip, Mercé; Salas-Puig, Xavier; Cara, Carlos

2013-08-01

Inflammation is one of the most important endogenous defence mechanisms in an organism. It has been suggested that inflammation plays an important role in the pathophysiology of a number of human epilepsies and convulsive disorders, and there is clinical and experimental evidence to suggest that inflammatory processes within the CNS may either contribute to or be a consequence of epileptogenesis. This review discusses evidence from human studies on the role of inflammation in epilepsy and highlights potential new targets in the inflammatory cascade for antiepileptic drugs. A number of mechanisms have been shown to be involved in CNS inflammatory reactions. These include an inflammatory response at the level of the blood-brain barrier (BBB), immune-mediated damage to the CNS, stress-induced release of inflammatory mediators and direct neuronal dysfunction or damage as a result of inflammatory reactions. Mediators of inflammation in the CNS include interleukin (IL)-1β, tumour necrosis factor-α, nuclear factor-κB and toll-like receptor-4 (TLR4). IL-1β, BBB and high-mobility group box-1-TLR4 signalling appear to be the most promising targets for anticonvulsant agents directed at inflammation. Such agents may provide effective therapy for drug-resistant epilepsies in the future.

Thought and language disorders in very early onset schizophrenia, schizoaffective disorder and bipolar disorder

Directory of Open Access Journals (Sweden)

Telma Pantano

Full Text Available Abstract Background Thought and language disorders are main features of adults with schizophrenia and bipolar disorders however studies on such abnormalities are scant in young patients with very early onset psychosis (VEOS. The aim of the present study is to assess the relationship between language and thought disorders in patients with very early onset schizophrenia (SCZ, schizoaffective disorders (SCA and bipolar disorders (BD. Method Forty-one patients (18 SCZ, 16 BD, and 7 SCA with mean age less than 15 years old were assessed through a series of neurocognitive and psycholinguistic tests, including the Thought, Language and Communication Scale (TLC. Results SCZ group performed worse in all tests as well as the TLC, followed by SCA and BD groups respectively. Thought disorders were related to deficits in executive functioning and semantic processing, and the metaphors’ test was the best predictor of TLC functioning. Discussion TD in SCZ, SCA and BD are one of the most important features in patients with VEOS and that the evaluation of metaphor comprehension can be an important instrument in the early detection of this disorder.

EMMPRIN, an upstream regulator of MMPs, in CNS biology.

Science.gov (United States)

Kaushik, Deepak Kumar; Hahn, Jennifer Nancy; Yong, V Wee

2015-01-01

Matrix metalloproteinases (MMPs) are engaged in pathologies associated with infections, tumors, autoimmune disorders and neurological dysfunctions. With the identification of an upstream regulator of MMPs, EMMPRIN (Extracellular matrix metalloproteinase inducer, CD147), it is relevant to address if EMMPRIN plays a role in the pathology of central nervous system (CNS) diseases. This would enable the possibility of a more upstream and effective therapeutic target. Indeed, conditions including gliomas, Alzheimer's disease (AD), multiple sclerosis (MS), and other insults such as hypoxia/ischemia show elevated levels of EMMPRIN which correlate with MMP production. In contrast, given EMMPRIN's role in CNS homeostasis with respect to regulation of monocarboxylate transporters (MCTs) and interactions with adhesion molecules including integrins, we need to consider that EMMPRIN may also serve important regulatory or protective functions. This review summarizes the current understanding of EMMPRIN's involvement in CNS homeostasis, its possible roles in escalating or reducing neural injury, and the mechanisms of EMMPRIN including and apart from MMP induction. Copyright © 2015 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Micropituitarism and cortical dysplasia: an unknown association of two uncommon CNS disorders

International Nuclear Information System (INIS)

Blinder, G.; Corat-Simon, J.; Hershkovitz, E.

2001-01-01

We describe a case of two known pathologies of the CNS in an unusual association: the concomitant presentation of the micropituitarism and cortical dysplasia. To our knowledge, this association is unreported to date. (orig.)

Micropituitarism and cortical dysplasia: an unknown association of two uncommon CNS disorders

Energy Technology Data Exchange (ETDEWEB)

Blinder, G. [MAR Bikur Cholim Hospital Jerusalem (MOR-MAR), Jerusalem (Israel); Corat-Simon, J. [Dept. of Radiology, Assaf Harofeh Medical Center, Zrifin, Beer Jakov (Israel); Hershkovitz, E. [Dept. of Pediatrics, Soroka Medical Center, Beer Sheba (Israel)

2001-06-01

We describe a case of two known pathologies of the CNS in an unusual association: the concomitant presentation of the micropituitarism and cortical dysplasia. To our knowledge, this association is unreported to date. (orig.)

Immune regulation and CNS autoimmune disease

DEFF Research Database (Denmark)

Antel, J P; Owens, T

1999-01-01

The central nervous system is a demonstrated target of both clinical and experimental immune mediated disorders. Immune regulatory mechanisms operative at the levels of the systemic immune system, the blood brain barrier, and within the CNS parenchyma are important determinants of the intensity...... and duration of the tissue directed injury. Convergence of research, involving direct manipulation of specific cells and molecular mediators in animal models and in vitro analysis of human immune and neural cells and tissues, is providing increasing insight into the role of these immune regulatory functions...

Bortezomib-related neuropathy may mask CNS relapse in multiple myeloma: A call for diligence.

Science.gov (United States)

Abid, Muhammad Bilal; De Mel, Sanjay; Abid, Muhammad Abbas; Tan, Kong Bing; Chng, Wee Joo

2016-07-02

Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM. A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance. Six months after ASCT she developed symptoms suggestive of peripheral neuropathy which was attributed to bortezomib. However the symptoms persisted despite discontinuation of bortezomib. Imaging and cerebrospinal fluid analysis subsequently confirmed a CNS relapse. CNS involvement in MM (CNS-MM) is uncommon and is considered an aggressive disease. Recently published literature has reported biomarkers with prognostic potential. However, isolated CNS relapse is even less common; an event which carries a very poor prognosis. Given the heterogeneous neurologic manifestations associated with MM, clinical suspicion may be masked by confounding factors such as bortezomib-based therapy. The disease may further remain incognito if the patient does not exhibit any of the high risk features and biomarkers associated with CNS involvement. In the era of proteasome inhibitor (PtdIns)/immunomodulator (IMID)-based therapy for MM which carries neurologic adverse effects, it is prudent to consider CNS relapse early. This case further highlights the need for more robust biomarkers to predict CNS relapse and use of newer novel agents which demonstrate potential for CNS penetration.

Isolated vasculitis of the CNS

International Nuclear Information System (INIS)

Block, F.; Reith, W.

2000-01-01

Vasculitis is a rare cause for disease of the CNS. The isolated vasculitis of the CNS is restricted to the CNS whereas other forms of vasculitis affect various organs including the CNS. Headache, encephalopathy, focal deficits and epileptic seizures are the major symptoms suggestive for vasculitis. One major criterion of the isolated vasculitis of the CNS is the lack of evidence for other vasculitis forms or for pathology of other organs. Angiography displays multifocal segmental stenosis of intracranial vessels. MRI demonstrates multiple lesions which in part show enhancement after gadolinium. A definite diagnosis can only be made on the grounds of biopsy from leptomeninges and parenchyma. Therapy consists of corticosteroids and cyclophosphamid. (orig.) [de

Observations at the CNS-PNS border of ventral roots connected to a neuroma

Directory of Open Access Journals (Sweden)

Sten Remahl

2010-10-01

Full Text Available Previous studies have shown that numerous sprouts originating from a neuroma, after nerve injury in neonatal animals, can invade spinal nerve roots. In this study the border between the central and peripheral nervous system (CNS-PNS border of ventral roots in kittens was examined with both light and electron microscopy after early postnatal sciatic nerve resection. A transient ingrowth of substance P positive axons was observed into the CNS, but no spouts remained 6 weeks after the injury. Using serial sections and electron microscopy it was possible to identify small bundles of unmyelinated axons that penetrated from the root fascicles for a short distance into the CNS. These axons ended blindly, sometimes with a growth cone-like terminal swelling filled with vesicles. The axon bundles were accompanied by p75 positive cells in both the root fascicles and the pia mater, but not in the CNS. It may thus be suggested that neurotrophin presenting p75 positive cells could facilitate axonal growth into the pia mater and that the lack of such cells in the CNS compartment might contribute to the failure of growth into the CNS. A maldevelopment of myelin sheaths at the CNS-PNS border of motor axons was observed and it seems possible that this could have consequences for the propagation of action potential across this region after neonatal nerve injury.

Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders.

Science.gov (United States)

Malykh, Andrei G; Sadaie, M Reza

2010-02-12

There is an increasing interest in nootropic drugs for the treatment of CNS disorders. Since the last meta-analysis of the clinical efficacy of piracetam, more information has accumulated. The primary objective of this systematic survey is to evaluate the clinical outcomes as well as the scientific literature relating to the pharmacology, pharmacokinetics/pharmacodynamics, mechanism of action, dosing, toxicology and adverse effects of marketed and investigational drugs. The major focus of the literature search was on articles demonstrating evidence-based clinical investigations during the past 10 years for the following therapeutic categories of CNS disorders: (i) cognition/memory; (ii) epilepsy and seizure; (iii) neurodegenerative diseases; (iv) stroke/ischaemia; and (v) stress and anxiety. In this article, piracetam-like compounds are divided into three subgroups based on their chemical structures, known efficacy and intended clinical uses. Subgroup 1 drugs include piracetam, oxiracetam, aniracetam, pramiracetam and phenylpiracetam, which have been used in humans and some of which are available as dietary supplements. Of these, oxiracetam and aniracetam are no longer in clinical use. Pramiracetam reportedly improved cognitive deficits associated with traumatic brain injuries. Although piracetam exhibited no long-term benefits for the treatment of mild cognitive impairments, recent studies demonstrated its neuroprotective effect when used during coronary bypass surgery. It was also effective in the treatment of cognitive disorders of cerebrovascular and traumatic origins; however, its overall effect on lowering depression and anxiety was higher than improving memory. As add-on therapy, it appears to benefit individuals with myoclonus epilepsy and tardive dyskinesia. Phenylpiracetam is more potent than piracetam and is used for a wider range of indications. In combination with a vasodilator drug, piracetam appeared to have an additive beneficial effect on various

Nanomedicines for the Treatment of CNS Diseases.

Science.gov (United States)

Reynolds, Jessica L; Mahato, Ram I

2017-03-01

Targeting and delivering macromolecular therapeutics to the central nervous system (CNS) has been a major challenge. The blood-brain barrier (BBB) is the main obstacle that must be overcome to allow compounds to reach their targets in the brain. Therefore, much effort has been channelled into improving transport of therapeutics across the BBB and into the CNS including the use of nanoparticles. In this thematic issue, several reviews and original research are presented that address "Nanomedicines for CNS Diseases." The articles in this issue are concentrated on either CNS-HIV disease or CNS tumors. In regards to CNS-HIV disease, there are two reviews that discuss the role of nanoparticles for improving the delivery of HIV therapeutics to the CNS. In addition, there are two original articles focusing on therapies for CNS-HIV, one of them uses nanoparticles for delivery of siRNA specific to a key protein in autophagy to microglia, and another discusses nanoparticle delivery of a soluble mediator to suppress neuroinflammation. Furthermore, a comprehensive review about gene therapy for CNS neurological diseases is also included. Finally, this issue also includes review articles on enhanced drug targeting to CNS tumors. These articles include a review on the use of nanoparticles for CNS tumors, a review on functionalization (ligands) of nanoparticles for drug targeting to the brain tumor by overcoming BBB, and the final review discusses the use of macrophages as a delivery vehicle to CNS tumors. This thematic issue provides a wealth of knowledge on using nanomedicines for CNS diseases.

Proceedings of the 2013 CINP summit: innovative partnerships to accelerate CNS drug discovery for improved patient care.

Science.gov (United States)

Phillips, Anthony George; Hongaard-Andersen, Peter; Moscicki, Richard A; Sahakian, Barbara; Quirion, Rémi; Krishnan, K Ranga Rama; Race, Tim

2014-12-25

Central nervous system (CNS) diseases and, in particular, mental health disorders, are becoming recognized as the health challenge of the 21(st) century. Currently, at least 10% of the global population is affected by a mental health disorder, a figure that is set to increase year on year. Meanwhile, the rate of development of new CNS drugs has not increased for many years, despite unprecedented levels of investment. In response to this state of affairs, the Collegium Internationale Neuro-Psychopharmacologicum (CINP) convened a summit to discuss ways to reverse this disturbing trend through new partnerships to accelerate CNS drug discovery. The objectives of the Summit were to explore the issues affecting the value chain (i.e. the chain of activities or stakeholders that a company engages in/with to deliver a product to market) in brain research, thereby gaining insights from key stakeholders and developing actions to address unmet needs; to identify achievable objectives to address the issues; to develop action plans to bring about measurable improvements across the value chain and accelerate CNS drug discovery; and finally, to communicate recommendations to governments, the research and development community, and other relevant stakeholders. Summit outputs include the following action plans, aligned to the pressure points within the brain research-drug development value chain: Code of conduct dealing with conflict of interest issues, Prevention, early diagnosis, and treatment, Linking science and regulation, Patient involvement in trial design, definition of endpoints, etc., Novel trial design, Reproduction and confirmation of data, Update of intellectual property (IP) laws to facilitate repurposing and combination therapy (low priority), Large-scale, global patient registries, Editorials on nomenclature, biomarkers, and diagnostic tools, and Public awareness, with brain disease advocates to attend G8 meetings and World Economic Forum (WEF) Annual meetings in

Organotypic Cultures as a Model to Study Adult Neurogenesis in CNS Disorders

Directory of Open Access Journals (Sweden)

Fabio Cavaliere

2016-01-01

Full Text Available Neural regeneration resides in certain specific regions of adult CNS. Adult neurogenesis occurs throughout life, especially from the subgranular zone of hippocampus and the subventricular zone, and can be modulated in physiological and pathological conditions. Numerous techniques and animal models have been developed to demonstrate and observe neural regeneration but, in order to study the molecular and cellular mechanisms and to characterize multiple types of cell populations involved in the activation of neurogenesis and gliogenesis, investigators have to turn to in vitro models. Organotypic cultures best recapitulate the 3D organization of the CNS and can be explored taking advantage of many techniques. Here, we review the use of organotypic cultures as a reliable and well defined method to study the mechanisms of neurogenesis under normal and pathological conditions. As an example, we will focus on the possibilities these cultures offer to study the pathophysiology of diseases like Alzheimer disease, Parkinson’s disease, and cerebral ischemia.

Melanocortin signaling in the CNS directly regulates circulating cholesterol

OpenAIRE

Perez-Tilve, Diego; Hofmann, Susanna M; Basford, Joshua; Nogueiras, Ruben; Pfluger, Paul T; Patterson, James T; Grant, Erin; Wilson-Perez, Hilary E; Granholm, Norman A; Arnold, Myrtha; Trevaskis, James L; Butler, Andrew A; Davidson, William S; Woods, Stephen C; Benoit, Stephen C

2010-01-01

Cholesterol circulates in the blood in association with triglycerides and other lipids, and elevated blood low-density lipoprotein cholesterol carries a risk for metabolic and cardiovascular disorders, whereas high-density lipoprotein (HDL) cholesterol in the blood is thought to be beneficial. Circulating cholesterol is the balance among dietary cholesterol absorption, hepatic synthesis and secretion, and the metabolism of lipoproteins by various tissues. We found that the CNS is also an impo...

Neuropsychological screening as a standard of care during discharge from psychiatric hospitalization: the preliminary psychometrics of the CNS Screen.

Science.gov (United States)

Levy, Boaz; Celen-Demirtas, Selda; Surguladze, Tinatin; Eranio, Sara; Ellison, James

2014-03-30

Cost-prohibitive factors currently prevent a warranted integration of neuropsychological screenings into routine psychiatric evaluations, as a standard of care. To overcome this challenge, the current study examined the psychometric properties of a new computerized measure-the CNS Screen. One hundred and twenty six psychiatric inpatients completed the CNS Screen, the Montreal Cognitive Assessment (MoCA), and the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR₁₆) on the day of hospital discharge. Statistical analysis established convergent validity with a moderate correlation between the self-administered CNS Screen and the clinician-administered MoCA (r=0.64). Discriminant validity was implicated by a non-significant correlation with the QIDS-SR₁₆. Concurrent validity was supported by a moderate, negative correlation with patients' age (r=-0.62). In addition, consistent with previous findings, patients with psychotic disorders exhibited significantly poorer performance on the CNS Screen than patients with a mood disorder. Similarly, patients with a formal disability status scored significantly lower than other patients. The CNS Screen was well tolerated by all patients. With further development, this type of measure may provide a cost-effective approach to expanding neuropsychological screenings on inpatient psychiatric units. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Disease Type- and Status-Specific Alteration of CSF Metabolome Coordinated with Clinical Parameters in Inflammatory Demyelinating Diseases of CNS.

Directory of Open Access Journals (Sweden)

Soo Jin Park

Full Text Available Central nervous system (CNS inflammatory demyelinating diseases (IDDs are a group of disorders with different aetiologies, characterized by inflammatory lesions. These disorders include multiple sclerosis (MS, neuromyelitis optica spectrum disorder (NMOSD, and idiopathic transverse myelitis (ITM. Differential diagnosis of the CNS IDDs still remains challenging due to frequent overlap of clinical and radiological manifestation, leading to increased demands for new biomarker discovery. Since cerebrospinal fluid (CSF metabolites may reflect the status of CNS tissues and provide an interfacial linkage between blood and CNS tissues, we explored multi-component biomarker for different IDDs from CSF samples using gas chromatography mass spectrometry-based metabolite profiling coupled to multiplex bioinformatics approach. We successfully constructed the single model with multiple metabolite variables in coordinated regression with clinical characteristics, expanded disability status scale, oligoclonal bands, and protein levels. The multi-composite biomarker simultaneously discriminated four different immune statuses (a total of 145 samples; 54 MS, 49 NMOSD, 30 ITM, and 12 normal controls. Furthermore, systematic characterization of transitional metabolic modulation identified relapse-associated metabolites and proposed insights into the disease network underlying type-specific metabolic dysfunctionality. The comparative analysis revealed the lipids, 1-monopalmitin and 1-monostearin were common indicative for MS, NMOSD, and ITM whereas fatty acids were specific for the relapse identified in all types of IDDs.

Systematic review of the neurobiological relevance of chemokines to psychiatric disorders

Directory of Open Access Journals (Sweden)

Michael eStuart

2015-09-01

Full Text Available Psychiatric disorders are highly prevalent and disabling conditions of increasing public health relevance. Much recent research has focused on the role of cytokines in the pathophysiology of psychiatric disorders; however the related family of immune proteins designated chemokines has been relatively neglected. Chemokines were originally identified as having chemotactic function on immune cells, however recent evidence has begun to elucidate novel, brain-specific functions of these proteins of relevance to the mechanisms of psychiatric disorders. A systematic review of both human and animal literature in the PubMed and Google Scholar databases was undertaken. After application of all inclusion and exclusion criteria, 157 references were remained for the review. Some early mechanistic evidence does associate select chemokines with the neurobiological processes, including neurogenesis, modulation of the neuroinflammatory response, regulation of the HPA axis, and modulation of neurotransmitter systems. This early evidence however does not clearly demonstrate any specificity for a certain psychiatric disorder, but is primarily relevant to mechanisms which are shared across disorders. Notable exceptions include CCL11 which has recently been shown to impair hippocampal function in aging - of distinct relevance to Alzheimer’s disease and depression in the elderly, and prenatal exposure to CXCL8 that may disrupt early neurodevelopmental periods predisposing to schizophrenia. Pro-inflammatory chemokines, such as CCL2, CCL7, CCL8, CCL12, CCL13, have been shown to drive chemotaxis of pro-inflammatory cells to the inflamed or injured CNS. Likewise, CX3CL has been implicated in promoting glial cells activation, proinflammatory cytokines secretion, expression of ICAM-1 and recruitment of CD4+ T-cells into the CNS during neuroinflammatory processes. With further translational research, chemokines may present novel diagnostic and/or therapeutic targets in

Systematic Review of the Neurobiological Relevance of Chemokines to Psychiatric Disorders.

Science.gov (United States)

Stuart, Michael J; Singhal, Gaurav; Baune, Bernhard T

2015-01-01

Psychiatric disorders are highly prevalent and disabling conditions of increasing public health relevance. Much recent research has focused on the role of cytokines in the pathophysiology of psychiatric disorders; however, the related family of immune proteins designated chemokines has been relatively neglected. Chemokines were originally identified as having chemotactic function on immune cells; however, recent evidence has begun to elucidate novel, brain-specific functions of these proteins of relevance to the mechanisms of psychiatric disorders. A systematic review of both human and animal literature in the PubMed and Google Scholar databases was undertaken. After application of all inclusion and exclusion criteria, 157 references were remained for the review. Some early mechanistic evidence does associate select chemokines with the neurobiological processes, including neurogenesis, modulation of the neuroinflammatory response, regulation of the hypothalamus-pituitary-adrenal axis, and modulation of neurotransmitter systems. This early evidence however does not clearly demonstrate any specificity for a certain psychiatric disorder, but is primarily relevant to mechanisms which are shared across disorders. Notable exceptions include CCL11 that has recently been shown to impair hippocampal function in aging - of distinct relevance to Alzheimer's disease and depression in the elderly, and pre-natal exposure to CXCL8 that may disrupt early neurodevelopmental periods predisposing to schizophrenia. Pro-inflammatory chemokines, such as CCL2, CCL7, CCL8, CCL12, and CCL13, have been shown to drive chemotaxis of pro-inflammatory cells to the inflamed or injured CNS. Likewise, CX3CL has been implicated in promoting glial cells activation, pro-inflammatory cytokines secretion, expression of ICAM-1, and recruitment of CD4+ T-cells into the CNS during neuroinflammatory processes. With further translational research, chemokines may present novel diagnostic and

Early intervention for post-traumatic stress disorder.

Science.gov (United States)

Bryant, Richard A

2007-02-01

The potentially debilitating effect of posttraumatic stress disorder (PTSD) has created much interest in early intervention strategies that can reduce PTSD. This review critiques the evidence for psychological debriefing approaches and alternate early intervention strategies. The review critiques the randomized controlled trials of psychological debriefing, and early provision of cognitive behavior therapy. The latter approach involves therapy attention on acutely traumatized individuals who are high risk for PTSD development, and particularly in people with acute stress disorder (ASD). Psychological debriefing does not prevent PTSD. Cognitive behaviour therapy strategies have proven efficacy in reducing subsequent PTSD in ASD populations. Despite the promising evidence for early provision of CBT, many people do not benefit from CBT. This review concludes with consideration of major challenges facing early intervention approaches in the context of terrorist attacks and mass disasters.

LATE-BREAKING ABSTRACT: Early relapse of non-small cell lung cancer (NSCLC) found after CNS-symptoms

DEFF Research Database (Denmark)

Hansen, Niels-Chr. G.; Laursen, Christian B.; Jeppesen, Stefan S.

2016-01-01

whether the introduction in 2010 of follow-up by CT of thorax and upper abdomen every three months has reduced the incidence of relapse suspected from CNS-symptoms.Results: All 827 NSCLC patients from Funen completing curative treatment from 2005 to 2013 were included. The total number of relapses found...... or III were found.Conclusion: CT-based follow-up has not reduced the incidence of relapse suspected from CNS-symptoms in stage II-IV, and therefore we suggest routine MR of the brain before curative treatment for this group of patients.Number, fractions(%), and [95%CI]Jan. 2005 - June 2010July 2010 - Dec...... after symptoms within 24 months decreased in the 3½ years after the introduction of CT-based follow-up, p < 0,001 (table), but the total fraction presenting with CNS-symptoms did not change, p = 0.296. Relapses after stage I cancer decreased (p = 0.025), while no differences or changes for stages II...

Rapid intranasal delivery of chloramphenicol acetyltransferase in the active form to different brain regions as a model for enzyme therapy in the CNS.

Science.gov (United States)

Appu, Abhilash P; Arun, Peethambaran; Krishnan, Jishnu K S; Moffett, John R; Namboodiri, Aryan M A

2016-02-01

The blood brain barrier (BBB) is critical for maintaining central nervous system (CNS) homeostasis by restricting entry of potentially toxic substances. However, the BBB is a major obstacle in the treatment of neurotoxicity and neurological disorders due to the restrictive nature of the barrier to many medications. Intranasal delivery of active enzymes to the brain has therapeutic potential for the treatment of numerous CNS enzyme deficiency disorders and CNS toxicity caused by chemical threat agents. The aim of this work is to provide a sensitive model system for analyzing the rapid delivery of active enzymes into various regions of the brain with therapeutic bioavailability. We tested intranasal delivery of chloramphenicol acetyltransferase (CAT), a relatively large (75kD) enzyme, in its active form into different regions of the brain. CAT was delivered intranasally to anaesthetized rats and enzyme activity was measured in different regions using a highly specific High Performance Thin Layer Chromatography (HP-TLC)-radiometry coupled assay. Active enzyme reached all examined areas of the brain within 15min (the earliest time point tested). In addition, the yield of enzyme activity in the brain was almost doubled in the brains of rats pre-treated with matrix metalloproteinase-9 (MMP-9). Intranasal administration of active enzymes in conjunction with MMP-9 to the CNS is both rapid and effective. The present results suggest that intranasal enzyme therapy is a promising method for counteracting CNS chemical threat poisoning, as well as for treating CNS enzyme deficiency disorders. Published by Elsevier B.V.

Intraoperative squash smear cytology in CNS lesions: A study of 150 pediatric cases

Directory of Open Access Journals (Sweden)

Arpita Jindal

2017-01-01

Full Text Available Background: Tumors of the central nervous system in the pediatric age group occur relatively frequently during the early years of life. Brain tumors are the most common solid malignancies of childhood and only second to acute childhood leukemia. Squash cytology is an indispensable diagnostic aid to central nervous system (CNS lesions. The definitive diagnosis of brain lesions is confirmed by histological examination. Aim: To study the cytology of CNS lesions in pediatric population and correlate it with histopathology. Materials and Methods: One hundred and fifty cases of CNS lesions in pediatric patients were studied over a period of 2 years. Intraoperative squash smears were prepared, stained with hematoxylin and eosin, and examined. Remaining sample was subjected to histopathological examination. Results: Medulloblastoma (24.0% was the most frequently encountered tumor followed by pilocyctic astrocytoma (21.33% and ependymoma (13.33%. Diagnostic accuracy of squash smear technique was 94.67% when compared with histological diagnosis. Conclusion: Smear cytology is a fairly accurate tool for intraoperative CNS consultations.

BOBATH THERAPY IN CORRECTION OF PSYCHOMOTOR DEVELOPMENT OF CHILDREN WITH ORGANIC INJURIES CNS

OpenAIRE

Bukhovets, B. O.; Romanchuk, A. P.

2014-01-01

The article represents therapy of Bobath such as one of the most effective author method which use in correction psychomotor development of children with disorders of musculoskeletal system. Bobath method is not new in the correction of movement disorders since last century and still supplementing and improving. In this work highlight topic of the effective use Bobath therapy in correction of psychomotor development in children age 3 – 6 years with organic involvement CNS. the experiment w...

Application of empowerment theory for CNS practice.

Science.gov (United States)

Carlson-Catalano, J M

1993-11-01

Power is necessary for the clinical nurse specialist (CNS) to successfully conduct objectives of practice in bureaucratic hospital settings. To obtain power, the CNS could use strategies of an empowerment theory to fully operationalize roles in hospitals. This article will discuss how the CNS may be empowered utilizing strategies in four empowering categories. In addition, the many benefits of empowering the CNS are reviewed.

Early wound site seeding in a patient with CNS high-grade neuroepithelial tumor with BCOR alteration: A case report.

Science.gov (United States)

Kirkman, Matthew A; Pickles, Jessica C; Fairchild, Amy R; Avery, Aimee; Pietsch, Torsten; Jacques, Thomas S; Aquilina, Kristian

2018-05-30

Advances in molecular profiling have facilitated the emergence of newly defined entities of central nervous system tumor, including CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR). Relatively little is known about the clinical behaviour of these newly-characterized tumors. We describe a pediatric male patient with CNS HGNET-BCOR who developed seeding of the tumor into the site of the surgical wound within months of surgery for resection of a residual posterior fossa tumor. This case emphasises three important points. First, CNS HGNET-BCOR can be aggressive tumors that necessitate close clinical and radiological surveillance. Second, surveillance imaging in such cases should incorporate the surgical incision site into the field of view, and this should be closely scrutinised to ensure the timely detection of wound site seeding. Third, wound site seeding may still occur despite the use of meticulous surgical techniques. Copyright © 2018. Published by Elsevier Inc.

Effects of x rays on the morphology and physiology of the CNS blood vessels of mice

Energy Technology Data Exchange (ETDEWEB)

Gladysz, J [Akademia Medyczna, Poznan (Poland)

1974-01-01

Irradiation of the CNS of mice with 4000 to 7600 R produces transitional disorder of the permeability of vascular walls, followed by a permanent (irreversible) degenerative lesion of blood capillaries and the surrounding astrogial cells. Intensity of this alterations may however not be the same in different terminal blood vessels. It is very likely that the above described lesion appearing in the acute phase can be the main cause of further alterations in the CNS which are observed in late phase of postradiation disease.

Identifying early indicators in bipolar disorder: a qualitative study.

Science.gov (United States)

Benti, Liliane; Manicavasagar, Vijaya; Proudfoot, Judy; Parker, Gordon

2014-06-01

The identification of early markers has become a focus for early intervention in bipolar disorder. Using a retrospective, qualitative methodology, the present study compares the early experiences of participants with bipolar disorder to those with unipolar depression up until their first diagnosed episode. The study focuses on differences in early home and school environments as well as putative differences in personality characteristics between the two groups. Finally we a compare and contrast prodromal symptoms in these two populations. Thirty-nine participants, 20 diagnosed with unipolar depression and 19 diagnosed with bipolar disorder, took part in the study. A semi-structured interview was developed to elicit information about participants' experiences prior to their first episode. Participants with bipolar disorder reported disruptive home environments, driven personality features, greater emotion dysregulation and adverse experiences during the school years, whereas participants with depression tended to describe more supportive home environments, and more compliant and introvert personality traits. Retrospective data collection and no corroborative evidence from other family members. No distinction was made between bipolar I and bipolar II disorder nor between melancholic and non-melancholic depression in the sample. Finally the study spanned over a 12-month period which does not allow for the possibility of diagnostic reassignment of some of the bipolar participants to the unipolar condition. These findings indicate that there may be benefits in combining both proximal and distal indicators in identifying a bipolar disorder phenotype which, in turn, may be relevant to the development of early intervention programs for young people with bipolar disorder.

Drug induced increases in CNS dopamine alter monocyte, macrophage and T cell functions: implications for HAND

Science.gov (United States)

Gaskill, Peter J.; Calderon, Tina M.; Coley, Jacqueline S.; Berman, Joan W.

2013-01-01

Central nervous system (CNS) complications resulting from HIV infection remain a major public health problem as individuals live longer due to the success of combined antiretroviral therapy (cART). As many as 70% of HIV infected people have HIV associated neurocognitive disorders (HAND). Many HIV infected individuals abuse drugs, such as cocaine, heroin or methamphetamine, that may be important cofactors in the development of HIV CNS disease. Despite different mechanisms of action, all drugs of abuse increase extracellular dopamine in the CNS. The effects of dopamine on HIV neuropathogenesis are not well understood, and drug induced increases in CNS dopamine may be a common mechanism by which different types of drugs of abuse impact the development of HAND. Monocytes and macrophages are central to HIV infection of the CNS and to HAND. While T cells have not been shown to be a major factor in HIV-associated neuropathogenesis, studies indicate that T cells may play a larger role in the development of HAND in HIV infected drug abusers. Drug induced increases in CNS dopamine may dysregulate functions of, or increase HIV infection in, monocytes, macrophages and T cells in the brain. Thus, characterizing the effects of dopamine on these cells is important for understanding the mechanisms that mediate the development of HAND in drug abusers. PMID:23456305

Perspectives and new aspects of metalloproteinases' inhibitors in therapy of CNS disorders: from chemistry to medicine.

Science.gov (United States)

Boguszewska-Czubara, Anna; Budzynska, Barbara; Skalicka-Wozniak, Krystyna; Kurzepa, Jacek

2018-05-13

Matrix metalloproteinases (MMPs) play a key role in remodelling of the extracellular matrix (ECM) and, at the same time, influence cell differentiation, migration, proliferation and survival. Their importance in variety of human diseases including cancer, rheumatoid arthritis, pulmonary emphysema and fibrotic disorders has been known for many years but special attention should be paid on the role of MMPs in the central nervous system (CNS) disorders. Till now, there are not many well documented physiological MMP target proteins in the brain and only some pathological ones. Numerous neurodegenerative diseases is a consequence or result in disturbed remodeling of brain ECM, therefore proper action of MMPs as well as control of their activity may play crucial roles in the development and the progress of these diseases. In present review we discuss the role of metalloproteinase inhibitors, from the well-known natural endogenous tissue inhibitors of metalloproteinases (TIMPs) through exogenous synthetic ones like (4-phenoxyphenylsulfonyl)methylthiirane (SB-3CT), tetracyclines, batimastat (BB-94) and FN-439. As the MMP-TIMP system has been well described in physiological development as well as in pathological conditions mainly in neoplasctic diseases, the knowledge about the enzymatic system in mammalian brain tissue remain still poorly understood in this context. Therefore, we focus on MMPs inhibition in the context of physiological function of adult brain as well as pathological conditions including neurodegenerative diseases, brain injuries and others. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Correlates of Early Assessment of Neurodevelopmental Disorders in Lebanon

Science.gov (United States)

Dirani, Leyla Akoury; Salamoun, Mariana

2014-01-01

Children with neurodevelopmental disorders who receive early therapeutic interventions present a better developmental pathway than children who do not. Early assessment of neurodevelopmental disorders is the first step in this process. This study aims at describing the variables that are in play in the first assessment of children with autism…

Do young adults with bipolar disorder benefit from early intervention?

DEFF Research Database (Denmark)

Kessing, Lars Vedel; Hansen, Hanne Vibe; Christensen, Ellen Margrethe

2014-01-01

BACKGROUND: It is unknown whether young adults with bipolar disorder are able to benefit from early intervention combining optimised pharmacological treatment and group psychoeducation. The aim of the present report was to compare the effects of early intervention among patients with bipolar...... disorder aged 18-25 years to that of patients aged 26 years or older. METHODS: Patients were randomised to early treatment in a specialised outpatient mood disorder clinic versus standard care. The primary outcome was risk of psychiatric re-hospitalisation. RESULTS: A total of 158 patients with mania/bipolar...... different, the observed differences of the point estimates was surprisingly larger for young adults suggesting that young adults with bipolar disorder may benefit even more than older adults from early intervention combining pharmacological treatment and group psychoeducation....

The Therapeutic Potential of Insulin-Like Growth Factor-1 in Central Nervous System Disorders

Science.gov (United States)

Costales, Jesse; Kolevzon, Alexander

2016-01-01

Central nervous system (CNS) development is a finely tuned process that relies on multiple factors and intricate pathways to ensure proper neuronal differentiation, maturation, and connectivity. Disruption of this process can cause significant impairments in CNS functioning and lead to debilitating disorders that impact motor and language skills, behavior, and cognitive functioning. Recent studies focused on understanding the underlying cellular mechanisms of neurodevelopmental disorders have identified a crucial role for insulin-like growth factor-1 (IGF-1) in normal CNS development. Work in model systems has demonstrated rescue of pathophysiological and behavioral abnormalities when IGF-1 is administered, and several clinical studies have shown promise of efficacy in disorders of the CNS, including autism spectrum disorder (ASD). In this review, we explore the molecular pathways and downstream effects of IGF-1 and summarize the results of completed and ongoing pre-clinical and clinical trials using IGF-1 as a pharmacologic intervention in various CNS disorders. This aim of this review is to provide evidence for the potential of IGF-1 as a treatment for neurodevelopmental disorders and ASD. PMID:26780584

Comparative analysis of acid sphingomyelinase distribution in the CNS of rats and mice following intracerebroventricular delivery.

Directory of Open Access Journals (Sweden)

Christopher M Treleaven

Full Text Available Niemann-Pick A (NPA disease is a lysosomal storage disorder (LSD caused by a deficiency in acid sphingomyelinase (ASM activity. Previously, we reported that biochemical and functional abnormalities observed in ASM knockout (ASMKO mice could be partially alleviated by intracerebroventricular (ICV infusion of hASM. We now show that this route of delivery also results in widespread enzyme distribution throughout the rat brain and spinal cord. However, enzyme diffusion into CNS parenchyma did not occur in a linear dose-dependent fashion. Moreover, although the levels of hASM detected in the rat CNS were determined to be within the range shown to be therapeutic in ASMKO mice, the absolute amounts represented less than 1% of the total dose administered. Finally, our results also showed that similar levels of enzyme distribution are achieved across rodent species when the dose is normalized to CNS weight as opposed to whole body weight. Collectively, these data suggest that the efficacy observed following ICV delivery of hASM in ASMKO mice could be scaled to CNS of the rat.

[Roles of Aquaporins in Brain Disorders].

Science.gov (United States)

Yasui, Masato

2015-06-01

Aquaporin (AQP) is a water channel protein that is expressed in the cell membranes. AQPs are related to several kinds of human diseases such as cataract. In the mammalian central nervous system (CNS), AQP4 is specifically expressed in the astrocyte membranes lining the perivascular and periventricular structures. AQP4 plays a role in the development of brain edema associated with certain brain disorders. Neuromyelitis optica (NMO) is a demyelinating disorder, and patients with NMO develop autoimmune antibodies against AQP4 in their serum. Therefore, AQP4 is involved in NMO pathogenesis. A new concept referred to as "glymphatic pathway" has been recently proposed to explain the lymphatic system in the CNS. Dysfunction of the "glymphatic pathway" may cause several neurodegenerative diseases and mood disorders. Importantly, AQP4 may play a role in the "glymphatic pathway". Further investigation of AQP4 in CNS disorders is necessary, and a new drug against AQP4 is expected.

Nanomaterials for delivery of nucleic acid to the central nervous system (CNS)

DEFF Research Database (Denmark)

Wang, Danyang; Wu, Lin-Ping

2017-01-01

-related disease, such as neurodegeneration and disorders, suitable, safe and effective drug delivery nanocarriers have to been developed to overcome the blood brain barrier (BBB), which is the most inflexible barrier in human body. Here, we highlight the structure and function of barriers in the central nervous...... system (CNS) and summary several types of nanomaterials which can be potentially used in the brain delivery nucleic acid....

Dual DNA methylation patterns in the CNS reveal developmentally poised chromatin and monoallelic expression of critical genes.

Directory of Open Access Journals (Sweden)

Jinhui Wang

Full Text Available As a first step towards discovery of genes expressed from only one allele in the CNS, we used a tiling array assay for DNA sequences that are both methylated and unmethylated (the MAUD assay. We analyzed regulatory regions of the entire mouse brain transcriptome, and found that approximately 10% of the genes assayed showed dual DNA methylation patterns. They include a large subset of genes that display marks of both active and silent, i.e., poised, chromatin during development, consistent with a link between differential DNA methylation and lineage-specific differentiation within the CNS. Sixty-five of the MAUD hits and 57 other genes whose function is of relevance to CNS development and/or disorders were tested for allele-specific expression in F(1 hybrid clonal neural stem cell (NSC lines. Eight MAUD hits and one additional gene showed such expression. They include Lgi1, which causes a subtype of inherited epilepsy that displays autosomal dominance with incomplete penetrance; Gfra2, a receptor for glial cell line-derived neurotrophic factor GDNF that has been linked to kindling epilepsy; Unc5a, a netrin-1 receptor important in neurodevelopment; and Cspg4, a membrane chondroitin sulfate proteoglycan associated with malignant melanoma and astrocytoma in human. Three of the genes, Camk2a, Kcnc4, and Unc5a, show preferential expression of the same allele in all clonal NSC lines tested. The other six genes show a stochastic pattern of monoallelic expression in some NSC lines and bi-allelic expression in others. These results support the estimate that 1-2% of genes expressed in the CNS may be subject to allelic exclusion, and demonstrate that the group includes genes implicated in major disorders of the CNS as well as neurodevelopment.

In vivo human apolipoprotein E isoform fractional turnover rates in the CNS.

Directory of Open Access Journals (Sweden)

Kristin R Wildsmith

Full Text Available Apolipoprotein E (ApoE is the strongest genetic risk factor for Alzheimer's disease and has been implicated in the risk for other neurological disorders. The three common ApoE isoforms (ApoE2, E3, and E4 each differ by a single amino acid, with ApoE4 increasing and ApoE2 decreasing the risk of Alzheimer's disease (AD. Both the isoform and amount of ApoE in the brain modulate AD pathology by altering the extent of amyloid beta (Aβ peptide deposition. Therefore, quantifying ApoE isoform production and clearance rates may advance our understanding of the role of ApoE in health and disease. To measure the kinetics of ApoE in the central nervous system (CNS, we applied in vivo stable isotope labeling to quantify the fractional turnover rates of ApoE isoforms in 18 cognitively-normal adults and in ApoE3 and ApoE4 targeted-replacement mice. No isoform-specific differences in CNS ApoE3 and ApoE4 turnover rates were observed when measured in human CSF or mouse brain. However, CNS and peripheral ApoE isoform turnover rates differed substantially, which is consistent with previous reports and suggests that the pathways responsible for ApoE metabolism are different in the CNS and the periphery. We also demonstrate a slower turnover rate for CSF ApoE than that for amyloid beta, another molecule critically important in AD pathogenesis.

Very Early-onset Schizophrenia with Secondary Onset Tic Disorder.

Science.gov (United States)

Telgote, Shilpa A; Pendharkar, Shreyas Shrikant; Kelkar, Amol D; Bhojane, Sachin

2017-01-01

Very early-onset schizophrenia (defined as an onset of psychosis before 13 years of age) is a rare and severe form of the disorder which is clinically and neurobiologically continuous with the adult-onset disorder. It is rarely reported tic disorder.

Attention-deficit/hyperactivity disorder in adolescence predicts onset of major depressive disorder through early adulthood.

Science.gov (United States)

Meinzer, Michael C; Lewinsohn, Peter M; Pettit, Jeremy W; Seeley, John R; Gau, Jeff M; Chronis-Tuscano, Andrea; Waxmonsky, James G

2013-06-01

The aim of this study was to examine the prospective relationship between a history of attention-deficit/hyperactivity disorder (ADHD) assessed in mid-adolescence and the onset of major depressive disorder (MDD) through early adulthood in a large school-based sample. A secondary aim was to examine whether this relationship was robust after accounting for comorbid psychopathology and psychosocial impairment. One thousand five hundred seven participants from the Oregon Adolescent Depression Project completed rating scales in adolescence and structured diagnostic interviews up to four times from adolescence to age 30. Adolescents with a lifetime history of ADHD were at significantly higher risk of MDD through early adulthood relative to those with no history of ADHD. ADHD remained a significant predictor of MDD after controlling for gender, lifetime history of other psychiatric disorders in adolescence, social and academic impairment in adolescence, stress and coping in adolescence, and new onset of other psychiatric disorders through early adulthood (hazard ratio, 1.81; 95% confidence interval, 1.04, 3.06). Additional significant, robust predictors of MDD included female gender, a lifetime history of an anxiety disorder, and poor coping skills in mid-adolescence, as well as the onset of anxiety, oppositional defiant disorder, and substance-use disorder after mid-adolescence. A history of ADHD in adolescence was associated with elevated risk of MDD through early adulthood and this relationship remained significant after controlling for psychosocial impairment in adolescence and co-occurring psychiatric disorders. Additional work is needed to identify the mechanisms of risk and to inform depression prevention programs for adolescents with ADHD. © 2013 Wiley Periodicals, Inc.

Alcohol intake alters immune responses and promotes CNS viral persistence in mice.

Science.gov (United States)

Loftis, Jennifer M; Taylor, Jonathan; Raué, Hans-Peter; Slifka, Mark K; Huang, Elaine

2016-10-01

Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans. Female and male BALB/c mice (n=94) were exposed to alcohol (ethanol; EtOH) and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either LCMV clone 13 (causes chronic infection similar to chronic HCV), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60days post-infection and continued to receive 24-h access to EtOH and water. Animals infected with LCMV clone 13 drank more EtOH, as compared to those with an acute or no viral infection. Six weeks after infection with LCMV clone 13, mice with EtOH exposure evidenced higher serum viral titers, as compared to mice without EtOH exposure. EtOH intake was also associated with reductions in virus-specific CD8(+) T cell frequencies (particularly CD11a(hi) subsets) and evidence of persistent CNS viremia in chronically infected mice. These findings support the hypothesis that EtOH use and chronic viral infection can result in combined toxic effects accelerating CNS damage and neuropsychiatric dysfunction and suggest that examining the role of EtOH in regulating viral persistence and CNS immunopathology in mice infected with LCMV can lead to a more comprehensive understanding of comorbid alcohol use disorder and chronic viral infection. Published by Elsevier B.V.

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.

Science.gov (United States)

Sturm, Dominik; Orr, Brent A; Toprak, Umut H; Hovestadt, Volker; Jones, David T W; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J; Balasubramanian, Gnanaprakash; Worst, Barbara C; Pajtler, Kristian W; Brabetz, Sebastian; Johann, Pascal D; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M; Remke, Marc; Phillips, Joanna J; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C; Schniederjan, Matthew J; Santi, Mariarita; Buccoliero, Anna M; Dahiya, Sonika; Kramm, Christof M; von Bueren, André O; von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U; Shalaby, Tarek; Grotzer, Michael; van Meter, Timothy; Monoranu, Camelia-Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S; Taylor, Michael D; Jones, Chris; Jabado, Nada; Karajannis, Matthias A; Eils, Roland; Schlesner, Matthias; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M; Ellison, David W; Korshunov, Andrey; Kool, Marcel

2016-02-25

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

SINS/CNS Nonlinear Integrated Navigation Algorithm for Hypersonic Vehicle

Directory of Open Access Journals (Sweden)

Yong-jun Yu

2015-01-01

Full Text Available Celestial Navigation System (CNS has characteristics of accurate orientation and strong autonomy and has been widely used in Hypersonic Vehicle. Since the CNS location and orientation mainly depend upon the inertial reference that contains errors caused by gyro drifts and other error factors, traditional Strap-down Inertial Navigation System (SINS/CNS positioning algorithm setting the position error between SINS and CNS as measurement is not effective. The model of altitude azimuth, platform error angles, and horizontal position is designed, and the SINS/CNS tightly integrated algorithm is designed, in which CNS altitude azimuth is set as measurement information. GPF (Gaussian particle filter is introduced to solve the problem of nonlinear filtering. The results of simulation show that the precision of SINS/CNS algorithm which reaches 130 m using three stars is improved effectively.

Analysis of perfusion weighted image of CNS lymphoma

International Nuclear Information System (INIS)

Lee, In Ho; Kim, Sung Tae; Kim, Hyung-Jin; Kim, Keon Ha; Jeon, Pyoung; Byun, Hong Sik

2010-01-01

Purpose: It is difficult to differentiate CNS lymphoma from other tumors such as malignant gliomas, metastases, or meningiomas with conventional MR imaging, because the imaging findings are overlapped between these tumors. The purpose of this study is to investigate the perfusion weighted MR imaging findings of CNS lymphomas and to compare the relative cerebral blood volume ratios between CNS lymphomas and other tumors such as high grade gliomas, metastases, or meningiomas. Materials and methods: We retrospectively reviewed MRI findings and clinical records in 13 patients with pathologically proven CNS lymphoma between January 2006 and November 2008. We evaluated the relative cerebral blood volume ratios of tumor, which were obtained by dividing the values obtained from the normal white matter on MRI. Results: Total 13 patients (M:F = 8:5; age range 46-67 years, mean age 52.3 years) were included. The CNS lymphomas showed relatively low values of maximum relative CBV ratio in most patients regardless of primary or secondary CNS lymphoma. Conclusion: Perfusion weighted image may be helpful in the diagnosis of CNS lymphoma in spite of primary or secondary or B cell or T cell.

Kynurenines in CNS disease: regulation by inflammatory cytokines

Science.gov (United States)

Campbell, Brian M.; Charych, Erik; Lee, Anna W.; Möller, Thomas

2014-01-01

The kynurenine pathway (KP) metabolizes the essential amino acid tryptophan and generates a number of neuroactive metabolites collectively called the kynurenines. Segregated into at least two distinct branches, often termed the “neurotoxic” and “neuroprotective” arms of the KP, they are regulated by the two enzymes kynurenine 3-monooxygenase and kynurenine aminotransferase, respectively. Interestingly, several enzymes in the pathway are under tight control of inflammatory mediators. Recent years have seen a tremendous increase in our understanding of neuroinflammation in CNS disease. This review will focus on the regulation of the KP by inflammatory mediators as it pertains to neurodegenerative and psychiatric disorders. PMID:24567701

Starting lithium prophylaxis early v. late in bipolar disorder

DEFF Research Database (Denmark)

Kessing, Lars Vedel; Vradi, Eleni; Andersen, Per Kragh

2014-01-01

BACKGROUND: No study has investigated when preventive treatment with lithium should be initiated in bipolar disorder. AIMS: To compare response rates among patients with bipolar disorder starting treatment with lithium early v. late. METHOD: Nationwide registers were used to identify all patients...... with a diagnosis of bipolar disorder in psychiatric hospital settings who were prescribed lithium during the period 1995-2012 in Denmark (n = 4714). Lithium responders were defined as patients who, following a stabilisation lithium start-up period of 6 months, continued lithium monotherapy without being admitted...... to hospital. Early v. late intervention was defined in two ways: (a) start of lithium following first contact; and (b) start of lithium following a diagnosis of a single manic/mixed episode. RESULTS: Regardless of the definition used, patients who started lithium early had significantly decreased rates of non...

Neurocognition in Early-Onset Schizophrenia and Schizoaffective Disorders

Science.gov (United States)

Hooper, Stephen R.; Giuliano, Anthony J.; Youngstrom, Eric A.; Breiger, David; Sikich, Linmarie; Frazier, Jean A.; Findling, Robert L.; McClellan, Jon; Hamer, Robert M.; Vitiello, Benedetto; Lieberman, Jeffrey A.

2010-01-01

Objective: We examined the neuropsychological functioning of youth enrolled in the NIMH funded trial, Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). We compared the baseline neuropsychological functioning of youth with schizophrenia (SZ, n = 79) to those with schizoaffective disorder (SA, n = 40), and examined the relationship…

The role of microbiome in central nervous system disorders

Science.gov (United States)

Wang, Yan; Kasper, Lloyd H.

2014-01-01

Mammals live in a co-evolutionary association with the plethora of microorganisms that reside at a variety of tissue microenvironments. The microbiome represents the collective genomes of these co-existing microorganisms, which is shaped by host factors such as genetics and nutrients but in turn is able to influence host biology in health and disease. Niche-specific microbiome, prominently the gut microbiome, has the capacity to effect both local and distal sites within the host. The gut microbiome has played a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities, and thus the concept of microbiome-gut-brain axis is emerging. Studies are revealing how diverse forms of neuro-immune and neuro-psychiatric disorders are correlated with or modulated by variations of microbiome, microbiota-derived products and exogenous antibiotics and probiotics. The microbiome poises the peripheral immune homeostasis and predisposes host susceptibility to CNS autoimmune diseases such as multiple sclerosis. Neural, endocrine and metabolic mechanisms are also critical mediators of the microbiome-CNS signaling, which are more involved in neuro-psychiatric disorders such as autism, depression, anxiety, stress. Research on the role of microbiome in CNS disorders deepens our academic knowledge about host-microbiome commensalism in central regulation and in practicality, holds conceivable promise for developing novel prognostic and therapeutic avenues for CNS disorders. PMID:24370461

Thyroid Hormone in the CNS: Contribution of Neuron-Glia Interaction.

Science.gov (United States)

Noda, Mami

2018-01-01

The endocrine system and the central nervous system (CNS) are intimately linked. Among hormones closely related to the nervous system, thyroid hormones (THs) are critical for the regulation of development and differentiation of neurons and neuroglia and hence for development and function of the CNS. T3 (3,3',5-triiodothyronine), an active form of TH, is important not only for neuronal development but also for differentiation of astrocytes and oligodendrocytes, and for microglial development. In adult brain, T3 affects glial morphology with sex- and age-dependent manner and therefore may affect their function, leading to influence on neuron-glia interaction. T3 is an important signaling factor that affects microglial functions such as migration and phagocytosis via complex mechanisms. Therefore, dysfunction of THs may impair glial function as well as neuronal function and thus disturb the brain, which may cause mental disorders. Investigations on molecular and cellular basis of hyperthyroidism and hypothyroidism will help us to understand changes in neuron-glia interaction and therefore consequent psychiatric symptoms. © 2018 Elsevier Inc. All rights reserved.

Early Maladaptive Schemas in the Patients with Somatoform Disorders

Directory of Open Access Journals (Sweden)

Ýsmet Kýrpýnar

2014-08-01

Method: We investigated a total of 28 patients aged 18-65 years, were diagnosed as Hypochondriasis or Somatization Disorder according to DSM-IV and 30 healthy controls. All participitans were assessed with The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-1. Data were obtained by using a Sociodemographic Questionnaire and Young Schema Questionnaire-Short Form 3. Results: The main age of patients was 36,71 ± 10.39. Most of the patients were female, married and housewives. All early maladaptive schema scores of patients with somatoform disorders were higher than healthy controls. Conclusion: All early maladaptive schemas have been found to be related to somatoform disorders in this study. The role of not a specific one but a total of maladaptive schemas in etiology may reflect the unspecific general sources of the tendency to somatoform disorders. [JCBPR 2014; 3(2.000: 84-93

Mast Cells and Innate Lymphoid Cells: Underappreciated Players in CNS Autoimmune Demyelinating Disease.

Science.gov (United States)

Brown, Melissa A; Weinberg, Rebecca B

2018-01-01

Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis, are autoimmune CNS inflammatory diseases. As a result of a breakdown in the relatively impermeable blood-brain barrier (BBB) in affected individuals, myelin-specific CD4 + and CD8 + T cells gain entry into the immune privileged CNS and initiate myelin, oligodendrocyte, and nerve axon destruction. However, despite the absolute requirement for T cells, there is increasing evidence that innate immune cells also play critical amplifying roles in disease pathogenesis. By modulating the character and magnitude of the myelin-reactive T cell response and regulating BBB integrity, innate cells affect both disease initiation and progression. Two classes of innate cells, mast cells and innate lymphoid cells (ILCs), have been best studied in models of allergic and gastrointestinal inflammatory diseases. Yet, there is emerging evidence that these cell types also exert a profound influence in CNS inflammatory disease. Both cell types are residents within the meninges and can be activated early in disease to express a wide variety of disease-modifying cytokines and chemokines. In this review, we discuss how mast cells and ILCs can have either disease-promoting or -protecting effects on MS and other CNS inflammatory diseases and how sex hormones may influence this outcome. These observations suggest that targeting these cells and their unique mediators can be exploited therapeutically.

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

DEFF Research Database (Denmark)

Sturm, Dominik; Orr, Brent A; Toprak, Umut H

2016-01-01

with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration...

CNS infections in immunocompetent patients

International Nuclear Information System (INIS)

Hartmann, K.M.; Zimmer, A.; Reith, W.

2008-01-01

This article gives a review of the most frequent infective agents reasonable for CNS infections in immunocompetent patients as well as their localisation and imaging specifications. MRI scanning is the gold standard to detect inflammatory conditions in the CNS. Imaging can be normal or nonspecifically altered although the infection is culturally or bioptically proven. There are no pathognomonic, pathogen-specific imaging criteria. The localization and dimension of the inflammation depends on the infection pathway. (orig.) [de

Bovine-associated CNS species resist phagocytosis differently

Science.gov (United States)

2013-01-01

Background Coagulase-negative staphylococci (CNS) cause usually subclinical or mild clinical bovine mastitis, which often remains persistent. Symptoms are usually mild, mostly only comprising slight changes in the appearance of milk and possibly slight swelling. However, clinical mastitis with severe signs has also been reported. The reasons for the differences in clinical expression are largely unknown. Macrophages play an important role in the innate immunity of the udder. This study examined phagocytosis and killing by mouse macrophage cells of three CNS species: Staphylococcus chromogenes (15 isolates), Staphylococcus agnetis (6 isolates) and Staphylococcus simulans (15 isolates). Staphylococcus aureus (7 isolates) was also included as a control. Results All the studied CNS species were phagocytosed by macrophages, but S. simulans resisted phagocytosis more effectively than the other CNS species. Only S. chromogenes was substantially killed by macrophages. Significant variations between isolates were seen in both phagocytosis and killing by macrophages and were more common in the killing assays. Significant differences between single CNS species and S. aureus were observed in both assays. Conclusion This study demonstrated that differences in the phagocytosis and killing of mastitis-causing staphylococci by macrophages exist at both the species and isolate level. PMID:24207012

Very early-onset schizophrenia with secondary onset tic disorder

OpenAIRE

Shilpa A Telgote; Shreyas Shrikant Pendharkar; Amol D Kelkar; Sachin Bhojane

2017-01-01

Very early-onset schizophrenia (defined as an onset of psychosis before 13 years of age) is a rare and severe form of the disorder which is clinically and neurobiologically continuous with the adult-onset disorder. It is rarely reported

Early trauma and mood disorders in youngsters

Directory of Open Access Journals (Sweden)

Caroline Elizabeth Konradt

2013-01-01

Full Text Available OBJECTIVE: To verify early experiences of childhood abuse and neglect among young with bipolar disorder (BD, major depression (MDD, and controls. METHOD: Case-control study nested to a population-based cross-sectional study. The diagnosis was performed via the structured clinical interview for DSM-IV Axis I Disorders (SCID. Traumatic events were analyzed using the Portuguese version - Questionário sobre Traumas na Infância (CTQ - based on the Childhood Trauma Questionnaire. RESULTS: The sample comprised 231 adolescents with 95 individuals in the control group, 82 with MDD and 54 with BD (32 of type I and 22 type II. The prevalence of trauma or violence in childhood was 42.2%; among those, 54.7% had BD, 62.2% had MDD and 18.1% were in the control group. Young people with BD or MDD obtained higher means in total CTQ and among their components when compared with those in the control group. DISCUSSION: Reports on early traumatic experiences were more frequent among young people with mood disorders than in the general population, corroborating the literature on the subject. In this sense, the traumatic experiences during childhood seemed to contribute to the onset of the disorder.

Early onset obsessive-compulsive disorder with and without tics.

Science.gov (United States)

de Mathis, Maria Alice; Diniz, Juliana B; Shavitt, Roseli G; Torres, Albina R; Ferrão, Ygor A; Fossaluza, Victor; Pereira, Carlos; Miguel, Eurípedes; do Rosario, Maria Conceicão

2009-07-01

Research suggests that obsessive-compulsive disorder (OCD) is not a unitary entity, but rather a highly heterogeneous condition, with complex and variable clinical manifestations. The aims of this study were to compare clinical and demographic characteristics of OCD patients with early and late age of onset of obsessive-compulsive symptoms (OCS); and to compare the same features in early onset OCD with and without tics. The independent impact of age at onset and presence of tics on comorbidity patterns was investigated. Three hundred and thirty consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD were evaluated: 160 patients belonged to the "early onset" group (EOG): before 11 years of age, 75 patients had an "intermediate onset" (IOG), and 95 patients were from the "late onset" group (LOG): after 18 years of age. From the 160 EOG, 60 had comorbidity with tic disorders. The diagnostic instruments used were: the Yale-Brown Obsessive Compulsive Scale and the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS), Yale Global Tics Severity Scale, and Structured Clinical Interview for DSM-IV Axis I Disorders-patient edition. Statistical tests used were: Mann-Whitney, full Bayesian significance test, and logistic regression. The EOG had a predominance of males, higher frequency of family history of OCS, higher mean scores on the "aggression/violence" and "miscellaneous" dimensions, and higher mean global DY-BOCS scores. Patients with EOG without tic disorders presented higher mean global DY-BOCS scores and higher mean scores in the "contamination/cleaning" dimension. The current results disentangle some of the clinical overlap between early onset OCD with and without tics.

CNS embryonal tumours: WHO 2016 and beyond.

Science.gov (United States)

Pickles, J C; Hawkins, C; Pietsch, T; Jacques, T S

2018-02-01

Embryonal tumours of the central nervous system (CNS) present a significant clinical challenge. Many of these neoplasms affect young children, have a very high mortality and therapeutic strategies are often aggressive with poor long-term outcomes. There is a great need to accurately diagnose embryonal tumours, predict their outcome and adapt therapy to the individual patient's risk. For the first time in 2016, the WHO classification took into account molecular characteristics for the diagnosis of CNS tumours. This integration of histological features with genetic information has significantly changed the diagnostic work-up and reporting of tumours of the CNS. However, this remains challenging in embryonal tumours due to their previously unaccounted tumour heterogeneity. We describe the recent revisions made to the 4th edition of the WHO classification of CNS tumours and review the main changes, while highlighting some of the more common diagnostic testing strategies. © 2017 British Neuropathological Society.

Pediatric Bipolar Disorder: Evidence for Prodromal States and Early Markers

Science.gov (United States)

Luby, Joan L.; Navsaria, Neha

2010-01-01

Background: Childhood bipolar disorder remains a controversial but increasingly diagnosed disorder that is associated with significant impairment, chronic course and treatment resistance. Therefore, the search for prodromes or early markers of risk for later childhood bipolar disorder may be of great importance for prevention and/or early…

Menstrual Disorders from Puberty to Early Adult Age: A Cross-Sectional Survey

Directory of Open Access Journals (Sweden)

Krupa Hitesh Shah

2017-10-01

Full Text Available Introduction: A female encounters various menstrual disorders from puberty to menopause. We evaluated menstrual disturbances in post-menarche age and young adult age. Aim: To know the prevalence and impact of menstrual abnormalities at early adolescent and young adult age and to evaluate course of disorders identified at early adolescent age. Materials and Methods: A cross-sectional survey was carried out through self-administered questionnaire on 367 consented students at Melaka Manipal Medical College at Manipal, during December 2015- April 2016. Data were analysed by Statistical Package for the Social Sciences (SPSS 16.0 software. Results: Prevalence and pattern of menstrual disorders at early adolescent and at young adult age were noted. The mean age of menarche was 12.1 ±1.1 years. Menorrhagia was the most frequent (14.7% and 11.7% and polymenorrhea (7.6 % and 6% was least frequent menstrual disorder at adolescent age and young adult age respectively. Resolution of pubertal menstrual disorders was observed in all disorders, but noticed highest in oligomenorrhea (91%, (p-value <0.05. Prevalence of menstrual related disorder like dysmenorrhea was 88.7% at adolescent age and 67.6% at the young adult age. It was statistically significant reduction. Hindrance in academic performance and social behavior was noted more at young adult age, which was in 23.9% and 46.7% respectively (p-value <0.05. Conclusion: The most prevalent menstrual abnormality was menorrhagia at the early adolescent and the young adult age. Associated the most prevalent menstrual related symptoms were dysmenorrhea at early adolescent age, and premenstrual symptom at the young adult age. The study demonstrates the natural course (decreasing prevalence of all menstrual disorders from early adolescent to young adult age.

Autoantibody-induced internalization of CNS AQP4 water channel and EAAT2 glutamate transporter requires astrocytic Fc receptor.

Science.gov (United States)

Hinson, Shannon R; Clift, Ian C; Luo, Ningling; Kryzer, Thomas J; Lennon, Vanda A

2017-05-23

Aquaporin-4 (AQP4) water channel-specific IgG distinguishes neuromyelitis optica (NMO) from multiple sclerosis and causes characteristic immunopathology in which central nervous system (CNS) demyelination is secondary. Early events initiating the pathophysiological outcomes of IgG binding to astrocytic AQP4 are poorly understood. CNS lesions reflect events documented in vitro following IgG interaction with AQP4: AQP4 internalization, attenuated glutamate uptake, intramyelinic edema, interleukin-6 release, complement activation, inflammatory cell recruitment, and demyelination. Here, we demonstrate that AQP4 internalization requires AQP4-bound IgG to engage an astrocytic Fcγ receptor (FcγR). IgG-lacking Fc redistributes AQP4 within the plasma membrane and induces interleukin-6 release. However, AQP4 endocytosis requires an activating FcγR's gamma subunit and involves astrocytic membrane loss of an inhibitory FcγR, CD32B. Interaction of the IgG-AQP4 complex with FcγRs triggers coendocytosis of the excitatory amino acid transporter 2 (EAAT2). Requirement of FcγR engagement for internalization of two astrocytic membrane proteins critical to CNS homeostasis identifies a complement-independent, upstream target for potential early therapeutic intervention in NMO.

Evaluation of calcium, magnesium, zinc, aluminum and manganese deposition in bones and CNS of rats fed calcium-deficient diets

International Nuclear Information System (INIS)

Yasui, Masayuki; Ota, Kiichiro; Sasajima, Kazuhisa; Iwata, Shiro.

1994-01-01

The long term intake of unbalanced mineral diets has been reported to be one of the pathogenetic factors of central nervous system (CNS) degeneration, and the unbalanced mineral distribution in the bones clinically is expressed as a metabolic bone disorder or deposition of neurotoxic minerals/metals. The unbalanced mineral or metal diets in animals provoke the unbalanced mineral distribution in bones and soft tissues. In this study, the calcium (Ca), magnesium (Mg), zinc (Zn), aluminum (Al) and manganese (Mn) contents in the CNS and the bones of rats maintained on unbalanced mineral diets were analyzed to investigate the roles of bone on CNS degeneration. Male Wistar rats were maintained for 90 days on the following diets: (A) standard diet, (B) low Ca diet, (C) low Ca-Mg diet, (D) low Ca-Mg diet with high Al. Al and Mn contents were determined in the frontal cortex, spinal cord, lumbar spine and femur using inductively coupled plasma emission spectrometry (ICP) for Ca, Mg and Zn, and neutron activation analysis (NAA) for Al and Mn. Intake of low Ca and Mg with added Al in rats led to the abnormal distribution of metals or minerals in the bones and in the CNS. These results illustrate that unbalanced mineral diets and metal-metal interactions may lead to the irregular deposition of Al and Mn in the bones and ultimately in the CNS, thus inducing CNS degeneration. (author)

Parental and Child Characteristics Related to Early-Onset Disordered Eating: A Systematic Review.

Science.gov (United States)

Larsen, Pernille Stemann; Strandberg-Larsen, Katrine; Micali, Nadia; Andersen, Anne-Marie Nybo

2015-01-01

After participating in this activity, learners should be better able to: Evaluate the evidence regarding parental and child characteristics related to early-onset disordered eating. Eating disorders are rare in children, but disordered eating is common. Understanding the phenomenology of disordered eating in childhood can aid prevention of full-blown eating disorders. The purpose of this review is to systematically extract and synthesize the evidence on parental and child characteristics related to early-onset disordered eating. Systematic searches were conducted in PubMED/MEDLINE, EMBASE, and PsycInfo using the following search terms: eating disorder, disordered eating, problem eating, anorexia nervosa, bulimia nervosa, binge eating, child, preadolescent, and early onset. Studies published from 1990 to 2013 addressing parental and child characteristics of disordered eating in children aged 6 to 12 years were eligible for inclusion. The search was restricted to studies with cross-sectional, case-control, or longitudinal designs, studies in English, and with abstracts available. Forty-four studies fit these criteria. Most studies were based on community samples with a cross-sectional design. The included studies varied considerably in size, instruments used to assess early-onset disordered eating, and parental and child characteristics investigated. Important determinants included the following: higher body weight, previously reported disordered eating, body dissatisfaction, depression, parental disordered eating, and parental comments/concerns about child's weight and eating. The findings were inconsistent for sex, age, socioeconomic status, ethnicity, self-esteem/worth, and parental body weight. In conclusion, characteristics related to early-onset disordered eating have mainly been explored with a cross-sectional design. Full understanding of causal pathways will require good-quality longitudinal studies designed to address the influence of parental eating

Innate Interferons Regulate CNS Inflammation

DEFF Research Database (Denmark)

Dieu, Ruthe; Khorooshi, Reza M. H.; Mariboe, Anne

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) whose pathology is characterised by demyelination and axonal damage. This results from interplay between CNS-resident glia, infiltrating leukocytes and a plethora of cytokines and chemokines. Currently...... potential IFN-inducing receptor that signals through NF-kB. Receptor activator of NF-kB (RANK) belongs to the TNF-receptor superfamily and has been shown to induce IFN-beta in medullary thymic epithelial cells affecting autoimmune regulatory processes and osteoclast precursor cells in association to bone...

Attention deficit hyperactivity disorder symptoms mediate early-onset smoking

NARCIS (Netherlands)

Huizink, A.C.; Van Lier, P.A.C.; Crijnen, A.A.M.

2009-01-01

Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized

Attention Deficit Hyperactivity Disorder Symptoms Mediate Early-Onset Smoking

NARCIS (Netherlands)

Huizink, A.C.; Lier, P.A.C. van; Crijnen, A.A.M.

2009-01-01

Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized

Attention deficit hyperactivity disorder symptoms mediate early-onset smoking

NARCIS (Netherlands)

A.C. Huizink (Anja); P.A.C. van Lier (Pol); A.A.M. Crijnen (Alfons)

2008-01-01

textabstractBackground/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based,

Air pollution: mechanisms of neuroinflammation and CNS disease.

Science.gov (United States)

Block, Michelle L; Calderón-Garcidueñas, Lilian

2009-09-01

Air pollution has been implicated as a chronic source of neuroinflammation and reactive oxygen species (ROS) that produce neuropathology and central nervous system (CNS) disease. Stroke incidence and Alzheimer's and Parkinson's disease pathology are linked to air pollution. Recent reports reveal that air pollution components reach the brain; systemic effects that impact lung and cardiovascular disease also impinge upon CNS health. While mechanisms driving air pollution-induced CNS pathology are poorly understood, new evidence suggests that microglial activation and changes in the blood-brain barrier are key components. Here we summarize recent findings detailing the mechanisms through which air pollution reaches the brain and activates the resident innate immune response to become a chronic source of pro-inflammatory factors and ROS, culminating in CNS disease.

Early-Onset Bipolar Disorder: Characteristics and Outcomes in the Clinic.

Science.gov (United States)

Connor, Daniel F; Ford, Julian D; Pearson, Geraldine S; Scranton, Victoria L; Dusad, Asha

2017-12-01

To assess patient characteristics and clinician-rated outcomes for children diagnosed with early-onset bipolar disorder in comparison to a depressive disorders cohort from a single clinic site. To assess predictors of bipolar treatment response. Medical records from 714 consecutive pediatric patients evaluated and treated at an academic tertiary child and adolescent psychiatry clinic between 2006 and 2012 were reviewed. Charts of bipolar children (n = 49) and children with depressive disorders (n = 58) meeting study inclusion/exclusion criteria were compared on variables assessing clinical characteristics, treatments, and outcomes. Outcomes were assessed by using pre- and post-Clinical Global Impressions (CGI)-Severity and Children's Global Assessment Scale (CGAS) scores, and a CGI-Improvement score ≤2 at final visit determined responder status. Bipolar outcome predictors were assessed by using multiple linear regression. Clinic prevalence rates were 6.9% for early-onset bipolar disorder and 1.5% for very early-onset bipolar disorder. High rates of comorbid diagnoses, symptom severity, parental stress, and child high-risk behaviors were found in both groups. The bipolar cohort had higher rates of aggression and higher lifetime systems of care utilization. The final CGI and CGAS outcomes for unipolar depression patients differed statistically significantly from those for the bipolar cohort, reflecting better clinical status and more improvement at outcome for the depression patients. Both parent-reported Child Behavior Checklist total T-score at clinic admission and the number of lifetime systems-of-care for the child were significantly and inversely associated with improvement for the bipolar cohort. Early-onset bipolar disorder is a complex and heterogeneous psychiatric disorder. Evidence-based treatment should emphasize psychopharmacology with adjunctive family and individual psychotherapy. Strategies to improve engagement in treatment may be especially

[Basics of early intervention in children with autism spectrum disorders].

Science.gov (United States)

Zalaquett, Daniela F; Schönstedt, Marianne G; Angeli, Milagros; Herrrera, Claudia C; Moyano, Andrea C

2015-01-01

Autism Spectrum Disorders (ASD) are characterized by impairments in communication and social interaction, as well as restricted and repetitive patterns of behavior. They have a prevalence of 0.6% in the general population, although there are no national statistics. Even though their evolution is variable, it has been observed that early intervention is an important factor determining prognosis. The aim of this study is to update concepts regarding the current available evidence on the importance of early intervention. After analyzing the collected information, the importance of early intervention programs for children with ASD is confirmed, as well as the role of pediatricians and other health professionals in the early detection of these disorders. Copyright © 2015. Publicado por Elsevier España, S.L.U.

Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan.

Science.gov (United States)

Tay, Tuan Leng; Béchade, Catherine; D'Andrea, Ivana; St-Pierre, Marie-Kim; Henry, Mathilde S; Roumier, Anne; Tremblay, Marie-Eve

2017-01-01

Microglia are the predominant immune response cells and professional phagocytes of the central nervous system (CNS) that have been shown to be important for brain development and homeostasis. These cells present a broad spectrum of phenotypes across stages of the lifespan and especially in CNS diseases. Their prevalence in all neurological pathologies makes it pertinent to reexamine their distinct roles during steady-state and disease conditions. A major question in the field is determining whether the clustering and phenotypical transformation of microglial cells are leading causes of pathogenesis, or potentially neuroprotective responses to the onset of disease. The recent explosive growth in our understanding of the origin and homeostasis of microglia, uncovering their roles in shaping of the neural circuitry and synaptic plasticity, allows us to discuss their emerging functions in the contexts of cognitive control and psychiatric disorders. The distinct mesodermal origin and genetic signature of microglia in contrast to other neuroglial cells also make them an interesting target for the development of therapeutics. Here, we review the physiological roles of microglia, their contribution to the effects of environmental risk factors (e.g., maternal infection, early-life stress, dietary imbalance), and their impact on psychiatric disorders initiated during development (e.g., Nasu-Hakola disease (NHD), hereditary diffuse leukoencephaly with spheroids, Rett syndrome, autism spectrum disorders (ASDs), and obsessive-compulsive disorder (OCD)) or adulthood (e.g., alcohol and drug abuse, major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, eating disorders and sleep disorders). Furthermore, we discuss the changes in microglial functions in the context of cognitive aging, and review their implication in neurodegenerative diseases of the aged adult (e.g., Alzheimer's and Parkinson's). Taking into account the recent identification of microglia

Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan

Directory of Open Access Journals (Sweden)

Tuan Leng Tay

2018-01-01

Full Text Available Microglia are the predominant immune response cells and professional phagocytes of the central nervous system (CNS that have been shown to be important for brain development and homeostasis. These cells present a broad spectrum of phenotypes across stages of the lifespan and especially in CNS diseases. Their prevalence in all neurological pathologies makes it pertinent to reexamine their distinct roles during steady-state and disease conditions. A major question in the field is determining whether the clustering and phenotypical transformation of microglial cells are leading causes of pathogenesis, or potentially neuroprotective responses to the onset of disease. The recent explosive growth in our understanding of the origin and homeostasis of microglia, uncovering their roles in shaping of the neural circuitry and synaptic plasticity, allows us to discuss their emerging functions in the contexts of cognitive control and psychiatric disorders. The distinct mesodermal origin and genetic signature of microglia in contrast to other neuroglial cells also make them an interesting target for the development of therapeutics. Here, we review the physiological roles of microglia, their contribution to the effects of environmental risk factors (e.g., maternal infection, early-life stress, dietary imbalance, and their impact on psychiatric disorders initiated during development (e.g., Nasu-Hakola disease (NHD, hereditary diffuse leukoencephaly with spheroids, Rett syndrome, autism spectrum disorders (ASDs, and obsessive-compulsive disorder (OCD or adulthood (e.g., alcohol and drug abuse, major depressive disorder (MDD, bipolar disorder (BD, schizophrenia, eating disorders and sleep disorders. Furthermore, we discuss the changes in microglial functions in the context of cognitive aging, and review their implication in neurodegenerative diseases of the aged adult (e.g., Alzheimer’s and Parkinson’s. Taking into account the recent identification of

Memory in Early Onset Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder: Similarities and Differences

Science.gov (United States)

Udal, Anne H.; Oygarden, Bjorg; Egeland, Jens; Malt, Ulrik F.; Groholt, Berit

2012-01-01

Differentiating between early-onset bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) can be difficult. Memory problems are commonly reported in BD, and forgetfulness is among the diagnostic criteria for ADHD. We compared children and adolescents with BD (n = 23), ADHD combined type (ADHD-C; n = 26), BD + ADHD-C (n = 15),…

Early-onset Major Depressive Disorder in men is associated with childlessness.

Science.gov (United States)

Yates, William R; Meller, William H; Lund, Brian C; Thurber, Steve; Grambsch, Patricia L

2010-07-01

The self-reported number of children was compared for men and women from the National Epidemiologic Survey of Alcoholism and Related Conditions Survey (NESARC). Subjects with a diagnosis of major depressive disorder or bipolar disorder were compared to those without an axis I disorder. The effect of age, gender, marriage and diagnostic status on number of children was completed using multivariate analyses. Men with a history of major depressive disorder but not bipolar disorder reported higher rates of childlessness and lower mean number of children. This reduced number of children was related to an early age of onset of MDD. Thirty percent of men with an age of onset of MDD before 22 were childless compared to only 18.9% of men without an axis I disorder (Odds ratio=1.82, 95% CI=1.45-2.27). No effect of mood disorder on number of children was found in women with major depression or bipolar disorder. This study suggests that an early age of onset of major depressive disorder contributes to childlessness in men.

Psychosis, Mood and Behavioral Disorders in Usher Syndrome: Review of the Literature.

Science.gov (United States)

Domanico, Daniela; Fragiotta, Serena; Cutini, Alessandro; Grenga, Pier Luigi; Vingolo, Enzo Maria

2015-01-01

The aim of this review is to focus the current knowledge about mental and behavioral disorders in Usher syndrome. Previous studies described the presence of various mental disorders associated with Usher syndrome, suggesting possible mechanisms of association between these disorders. The most common manifestations are schizophrenia-like disorder and psychotic symptoms. Mood and behavioral disorders are rarely described, and often are associated with more complex cases in co-occurrence with other psychiatric disorders. Neuroimaging studies reported diffuse involvement of central nervous system (CNS) in Usher patients, suggesting a possible role of CNS damage in the pathogenesis of psychiatric manifestations. Genetic hypothesis and stress-related theories have also been proposed.

Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder.

Science.gov (United States)

Nassan, Malik; Croarkin, Paul E; Luby, Joan L; Veldic, Marin; Joshi, Paramjit T; McElroy, Susan L; Post, Robert M; Walkup, John T; Cercy, Kelly; Geske, Jennifer R; Wagner, Karen D; Cuellar-Barboza, Alfredo B; Casuto, Leah; Lavebratt, Catharina; Schalling, Martin; Jensen, Peter S; Biernacka, Joanna M; Frye, Mark A

2015-09-01

Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association. DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult-onset cases at age >19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early-onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects. Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04). These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Decreased Cognitive/CNS Function in Young Adults at Risk for Hypertension: Effects of Sleep Deprivation

Directory of Open Access Journals (Sweden)

James A. McCubbin

2012-01-01

Full Text Available Hypertension has been linked to impaired cognitive/CNS function, and some of these changes may precede development of frank essential hypertension. The stress and fatigue of sleep deprivation may exacerbate these cognitive changes in young adults at risk. We hypothesize that individuals at risk for hypertension will show significant declines in cognitive function during a night of sleep deprivation. Fifty-one young adults were recruited for 28-hour total sleep deprivation studies. Hypertension risk was assessed by mildly elevated resting blood pressure and by family history of hypertension. A series of cognitive memory tasks was given at four test sessions across the sleep deprivation period. Although initially comparable in cognitive performance, persons at risk showed larger declines across the night for several indices of working memory, including code substitution, category, and order recall. These results suggest that cognitive/CNS changes may parallel or precede blood pressure dysregulation in the early stages of hypertension development. The role of CNS changes in the etiology of essential hypertension is discussed.

Insulin-Like Growth Factor 1 and Related Compounds in the Treatment of Childhood-Onset Neurodevelopmental Disorders

Directory of Open Access Journals (Sweden)

Cyrus Vahdatpour

2016-09-01

Full Text Available Insulin-Like Growth Factor 1 (IGF-1 is a neurotrophic polypeptide with crucial roles to play in Central Nervous System (CNS growth, development and maturation. Following interrogation of the neurobiology underlying several neurodevelopmental disorders and Autism Spectrum Disorders (ASD, both recombinant IGF-1 (mecasermin and related derivatives, such as (1-3 IGF-1, have emerged as potential therapeutic approaches. Clinical pilot studies and early reports have supported the safety/preliminary efficacy of IGF-1 and related compounds in the treatment of Rett Syndrome, with evidence mounting for its use in Phelan McDermid Syndrome and Fragile X Syndrome. In broader ASD, clinical trials are ongoing. Here, we review the role of IGF-1 in the molecular etiologies of these conditions in addition to the accumulating evidence from early clinical studies highlighting the possibility of IGF-1 and related compounds as potential treatments for these childhood-onset neurodevelopmental disorders.

CNS adverse events associated with antimalarial agents. Fact or fiction?

NARCIS (Netherlands)

Phillips-Howard, P. A.; ter Kuile, F. O.

1995-01-01

CNS adverse drug events are dramatic, and case reports have influenced clinical opinion on the use of antimalarials. Malaria also causes CNS symptoms, thus establishing causality is difficult. CNS events are associated with the quinoline and artemisinin derivatives. Chloroquine, once considered too

Differential Neurodevelopmental Trajectories in Patients With Early-Onset Bipolar and Schizophrenia Disorders

Science.gov (United States)

Arango, Celso

2014-01-01

Schizophrenia and bipolar disorders share not only clinical features but also some risk factors such as genetic markers and childhood adversity, while other risk factors such as urbanicity and obstetric complications seem to be specific to schizophrenia. An intriguing question is whether the well-established abnormal neurodevelopment present in many children and adolescents who eventually develop schizophrenia is also present in bipolar patients. The literature on adult bipolar patients is controversial. We report data on a subgroup of patients with pediatric-onset psychotic bipolar disorder who seem to share some developmental trajectories with patients with early-onset schizophrenia. These early-onset psychotic bipolar patients have low intelligence quotient, more neurological signs, reduced frontal gray matter at the time of their first psychotic episode, and greater brain changes than healthy controls in a pattern similar to early-onset schizophrenia cases. However, patients with early-onset schizophrenia seem to have more social impairment, developmental abnormalities (eg, language problems), and lower academic achievement in childhood than early-onset bipolar patients. We suggest that some of these abnormal developmental trajectories are more related to the phenotypic features (eg, early-onset psychotic symptoms) of these 2 syndromes than to categorically defined Diagnostic and Statistical Manual of Mental Disorders disorders. PMID:24371326

Comparative antibiogram of coagulase-negative Staphylococci (CNS) associated with subclinical and clinical mastitis in dairy cows.

Science.gov (United States)

Bansal, B K; Gupta, D K; Shafi, T A; Sharma, S

2015-03-01

The present study was planned to determine the in vitro antibiotic susceptibility of coagulase-negative Staphylococci (CNS) strains isolated from clinical and subclinical cases of mastitis in dairy cows. Antibiotic sensitivity profile will be helpful to recommend early therapy at the field level prior to availability of CST results. The milk samples from cases of clinical mastitis received in Mastitis Laboratory, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana and those of subclinical mastitis collected during routine screening of state dairy farms, were subjected to microbial culture. Identification of CNS organisms was done by standard biochemical tests. Antibiotic sensitivity testing, based on 30 antibiotics belonging to 12 groups, was done on 58 randomly selected CNS isolates (clinical isolates: 41, subclinical isolates: 17). Isolates were highly susceptible to chloramphenicol (98.3%), gentamicin (93.1%), streptomycin (91.4%), linezolid (91.4%), ceftixozime (87.9%), cloxacillin (86.2%), clotrimazole (86.2%), bacitracin (86.2%), enrofloxacin (84.5%) and ceftrioxone + tazobactum (70.7%), while resistance was observed against amoxicillin (77.6%), penicillin (75.9%), ampicillin (74.1%) and cefoperazone (51.7%). Overall, isolates from clinical cases of mastitis had a higher resistance than subclinical isolates. CNS isolates were susceptible to chloramphenicol, gentamicin and streptomycin, while higher resistance was recorded against routinely used penicillin group.

Molecular stress response in the CNS of mice after systemic exposureto interferon-alpha, ionizing radiation and ketamine

Energy Technology Data Exchange (ETDEWEB)

Lowe, Xiu R.; Marchetti, Francesco; Lu, Xiaochen; Wyrobek, Andrew J.

2009-03-03

We previously showed that the expression of troponin T1 (Tnnt 1) was induced in the central nervous system (CNS) of adultmice 30 min after treatment with ketamine, a glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonist. We hypothesized that Tnnt 1 expression may be an early molecular biomarker of stress response in the CNS of mice. To further evaluate this hypothesis, we investigated the regional expression of Tnnt 1 in the mouse brain using RNA in situ hybridization 4 h after systemic exposure to interferon-a (IFN-a) and gamma ionizing radiation, both of which have be associated with wide ranges of neuropsychiatric complications. Adult B6C3F1 male mice were treated with either human IFN-a (a single i.p. injection at 1 x 105 IU/kg) or whole body gamma-radiation (10 cGy or 2 Gy). Patterns of Tnnt 1 transcript expression were compared in various CNS regions after IFN-a, radiation and ketamine treatments (previous study). Tnnt 1 expression was consistently induced in pyramidal neurons of cerebral cortex and hippocampus after all treatment regimens including 10 cGy of ionizing radiation. Regional expression of Tnnt 1 was induced in Purkinje cells of cerebellum after ionizing radiation and ketamine treatment; but not after IFN-a treatment. None of the three treatments induced Tnnt 1 expression in glial cells. The patterns of Tnnt 1 expression in pyramidal neurons of cerebral cortex andhippocampus, which are both known to play important roles in cognitive function, memory and emotion, suggest that the expression of Tnnt 1 may be an early molecular biomarker of induced CNS stress.

3rd ENRI International Workshop on ATM/CNS

CERN Document Server

2014-01-01

The Electronic Navigation Research Institute (ENRI) held its third　International Workshop on ATM / CNS in 2013 with the theme of "Drafting　the future sky". There is worldwide activity taking place in the research and development　of modern air traffic management (ATM) and its enabling technologies in　Communication, Navigation and Surveillance (CNS). Pioneering work is necessary to contribute to the global harmonization　of air traffic management and control. At this workshop, leading experts　in  research, industry and academia from around the world met to share　their ideas and approaches on ATM/CNS related topics.

CNS penetration of ART in HIV-infected children

NARCIS (Netherlands)

van den Hof, Malon; Blokhuis, Charlotte; Cohen, Sophie; Scherpbier, Henriette J.; Wit, Ferdinand W. N. M.; Pistorius, M. C. M.; Kootstra, Neeltje A.; Teunissen, Charlotte E.; Mathot, Ron A. A.; Pajkrt, Dasja

2018-01-01

Background: Paediatric data on CNS penetration of antiretroviral drugs are scarce. Objectives: To evaluate CNS penetration of antiretroviral drugs in HIV-infected children and explore associations with neurocognitive function. Patients and methods: Antiretroviral drug levels were measured in paired

Anti-α4 Antibody Treatment Blocks Virus Traffic to the Brain and Gut Early, and Stabilizes CNS Injury Late in Infection

OpenAIRE

Campbell, Jennifer H.; Ratai, Eva-Maria; Autissier, Patrick; Nolan, David J.; Tse, Samantha; Miller, Andrew D.; González, R. Gilberto; Salemi, Marco; Burdo, Tricia H.; Williams, Kenneth C.

2014-01-01

Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages a...

SYMPTOM PRESENTATIONS AND CLASSIFICATION OF AUTISM SPECTRUM DISORDER IN EARLY CHILDHOOD: APPLICATION TO THE DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD (DC:0-5).

Science.gov (United States)

Soto, Timothy; Giserman Kiss, Ivy; Carter, Alice S

2016-09-01

Over the past 5 years, a great deal of information about the early course of autism spectrum disorder (ASD) has emerged from longitudinal prospective studies of infants at high risk for developing ASD based on a previously diagnosed older sibling. The current article describes early ASD symptom presentations and outlines the rationale for defining a new disorder, Early Atypical Autism Spectrum Disorder (EA-ASD) to accompany ASD in the new revision of the ZERO TO THREE Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC:0-5) (in press) alternative diagnostic classification manual. EA-ASD is designed to identify children who are 9 to 36 months of age presenting with a minimum of (a) two social-communication symptoms and (b) one repetitive and restricted behavior symptom as well as (c) evidence of impairment, with the intention of providing these children with appropriately tailored services and improving the likelihood of optimizing their development. © 2016 Michigan Association for Infant Mental Health.

Biomarkers in early phase development of central nervous system drugs : a conceptual framework

NARCIS (Netherlands)

Post, Jeroen-Paul van der

2006-01-01

The main objective of this thesis is to provide a conceptual framework for the use of Central Nervous System (CNS) biomarkers in early phase clinical drug development. In the Introduction the current use of biomarkers in early CNS drug development is discussed. A conceptual framework for the

Palmitoylethanolamide in CNS health and disease.

Science.gov (United States)

Mattace Raso, Giuseppina; Russo, Roberto; Calignano, Antonio; Meli, Rosaria

2014-08-01

The existence of acylethanolamides (AEs) in the mammalian brain has been known for decades. Among AEs, palmitoylethanolamide (PEA) is abundant in the central nervous system (CNS) and conspicuously produced by neurons and glial cells. Antihyperalgesic and neuroprotective properties of PEA have been mainly related to the reduction of neuronal firing and to control of inflammation. Growing evidence suggest that PEA may be neuroprotective during CNS neurodegenerative diseases. Advances in the understanding of the physiology and pharmacology of PEA have potentiated its interest as useful biological tool for disease management. Several rapid non-genomic and delayed genomic mechanisms of action have been identified for PEA as peroxisome proliferator-activated receptor (PPAR)-α dependent. First, an early molecular control, through Ca(+2)-activated intermediate- and/or big-conductance K(+) channels opening, drives to rapid neuronal hyperpolarization. This is reinforced by the increase of the inward Cl(-) currents due to the modulation of the gamma aminobutyric acid A receptor and by the desensitization of the transient receptor potential channel type V1. Moreover, the gene transcription-mediated mechanism sustains the long-term anti-inflammatory effects, by reducing pro-inflammatory enzyme expression and increasing neurosteroid synthesis. Overall, the integration of these different modes of action allows PEA to exert an immediate and prolonged efficacious control in neuron signaling either on inflammatory process or neuronal excitability, maintaining cellular homeostasis. In this review, we will discuss the effect of PEA on metabolism, behavior, inflammation and pain perception, related to the control of central functions and the emerging evidence demonstrating its therapeutic efficacy in several neurodegenerative diseases. Copyright © 2014. Published by Elsevier Ltd.

Perceived Behavioral Changes in Early Multiple Sclerosis

Directory of Open Access Journals (Sweden)

Fabiana Souza Lima

2007-01-01

Full Text Available Acquired behavioral changes have essentially been described in advanced multiple sclerosis (MS. The present study was designed to determine whether behavioral modifications specifically related to the MS pathological process could be identified in the initial phase of the disease, as compared to control patients with chronic, relapsing and progressive inflammatory disorders not involving the central nervous system (CNS. Eighty-eight early MS patients (Expanded Disability Status Scale score ≤ 2.5 and 48 controls were tested. Perceived changes by informants in behavioral control, goal-directed behavior, decision making, emotional expression, insight and interpersonal relationships were assessed using the Iowa Scale of Personality Change (ISPC. Executive behavioral disturbances were screened using the Dysexecutive Questionnaire (DEX. The mean change between the premorbid and postmorbid ISPC ratings was similar in the MS [12.2 (SD 15.6] and in the control [11.5 (SD 15.1] group. The perceived behavioral changes (PBCs most frequently reported in both groups were lack of stamina, lability/moodiness, anxiety, vulnerability to stress and irritability. Pathological scores in the DEX were also similar in both groups. Correlations between PBCs and DEX scores were different in MS and control groups. MS patients with cognitive impairment had a marginally higher number of PBCs than control patients (p = 0.056 and a significantly higher DEXp score (p = 0.04. These results suggest that (1 PBCs occurring in early MS patients were not different from those induced by comparable chronic non-CNS disorders, (2 qualitative differences in the relationship between behavioral symptoms and executive-behavioral changes may exist between MS and control groups, and (3 behavioral symptoms seem associated with cognitive deficits in MS. We further plan to assess these observations longitudinally.

PEG minocycline-liposomes ameliorate CNS autoimmune disease.

Directory of Open Access Journals (Sweden)

Wei Hu

Full Text Available Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS. Minocycline, a potent inhibitor of matrix metalloproteinase (MMP-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG minocycline liposomes are effective in treating EAE.Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs, we determined that PEG minocycline-liposome preparations stabilized with CaCl(2 are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number.Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS.

Autism Spectrum Disorder Updates - Relevant Information for Early Interventionists to Consider.

Science.gov (United States)

Allen-Meares, Paula; MacDonald, Megan; McGee, Kristin

2016-01-01

Autism spectrum disorder (ASD) is a pervasive developmental disorder characterized by deficits in social communication skills as well as repetitive, restricted or stereotyped behaviors (1). Early interventionists are often found at the forefront of assessment, evaluation, and early intervention services for children with ASD. The role of an early intervention specialist may include assessing developmental history, providing group and individual counseling, working in partnership with families on home, school, and community environments, mobilizing school and community resources, and assisting in the development of positive early intervention strategies (2, 3). The commonality among these roles resides in the importance of providing up-to-date, relevant information to families and children. The purpose of this review is to provide pertinent up-to-date knowledge for early interventionists to help inform practice in working with individuals with ASD, including common behavioral models of intervention.

Patient factors predicting early dropout from psychiatric outpatient care for borderline personality disorder.

Science.gov (United States)

De Panfilis, Chiara; Marchesi, Carlo; Cabrino, Chiara; Monici, Alberto; Politi, Virginia; Rossi, Matteo; Maggini, Carlo

2012-12-30

Despite obvious clinical need, factors underlying early treatment discontinuation among 'real world' borderline personality disorder (BPD) patients are still unknown. This study investigates individual characteristics that can predict early (Disorders, fourth edition (DSM-IV) Personality. Sociodemographic, clinical and personality variables potentially relevant for dropout were assessed for all participants at baseline. Early dropouts (n=54) were compared to continuers (n=108) on all measures. Logistic regression was then used to identify independent predictors of early dropout. A history of suicide attempts predicted early discontinuation, whereas the presence of an eating disorder and of avoidant personality features protected from early dropout. If confirmed, these findings may help clinicians operating in general psychiatric settings with estimating the risk of premature treatment discontinuation, and stress the need to specifically address suicidal behaviours in order to improve treatment retention among borderline outpatients. In this regard, implementing general psychiatric care with specialised, evidence-based psychotherapeutic interventions may be deemed necessary. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Utility of FDG-PETCT and magnetic resonance spectroscopy in differentiating between cerebral lymphoma and non-malignant CNS lesions in HIV-infected patients

Energy Technology Data Exchange (ETDEWEB)

Westwood, Thomas D., E-mail: tdwestwood@googlemail.com [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Hogan, Celia, E-mail: celiahogan@hotmail.com [Monsall Unit, Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Pennine Acute Hospitals NHS Trust (United Kingdom); Julyan, Peter J., E-mail: Peter.Julyan@christie.nhs.uk [Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Coutts, Glyn, E-mail: Glyn.Coutts@christie.nhs.uk [Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Bonington, Suzie, E-mail: suzi.bonington@christie.nhs.uk [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Carrington, Bernadette, E-mail: Bernadette.Carrington@christie.nhs.uk [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Taylor, Ben, E-mail: Ben.taylor@christie.nhs.uk [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Khoo, Saye, E-mail: S.H.Khoo@liverpool.ac.uk [Department of Infectious Diseases and Tropical Medicine, Royal Liverpool Hospital, Liverpool (United Kingdom); Bonington, Alec, E-mail: Alec.Bonington@pat.nhs.uk [Monsall Unit, Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Pennine Acute Hospitals NHS Trust (United Kingdom)

2013-08-15

Background and purpose: In HIV infected patients, MRI cannot reliably differentiate between central nervous system (CNS) lymphoma and non-malignant CNS lesions, particularly cerebral toxoplasmosis (CTOX). This study prospectively investigates the utility of FDG PET-CT and magnetic resonance spectroscopy (MRS) in discriminating CNS lymphoma from non-malignant CNS lesions in HIV infected patients, and assesses the ability of FDG PET-CT to guide the use of early brain biopsy. Methods: 10 HIV patients with neurological symptoms and contrast enhancing lesions on MRI were commenced on anti-toxoplasmosis therapy before undergoing FDG PET-CT and MRS. Brain biopsies were sought in those with FDG PET-CT suggestive of CNS lymphoma, and in those with a negative FDG PET-CT scan who failed to respond to therapy. Final diagnosis was based on histology or treatment response. Results: Two patients were confirmed to have CNS lymphoma and FDG PET-CT was consistent with this diagnosis in both. Six patients had cerebral toxoplasmosis in all of whom FDG PET-CT was consistent with non-malignant disease. One patient had progressive multifocal leukoencephalopathy (PML), FDG PET-CT was equivocal. One patient had a haemorrhagic brain metastasis and FDG PET-CT wrongly suggested non-malignant disease. MRS was performed successfully in eight subjects: three results were suggestive of CNS lymphoma (one true positive, two false positive), four suggested CTOX (two false negative, two true negative), one scan was equivocal. Conclusion: FDG PET-CT correctly identified all cases of CNS lymphoma and CTOX, supporting its use in this situation. MRS was unhelpful in our cohort.

Utility of FDG-PETCT and magnetic resonance spectroscopy in differentiating between cerebral lymphoma and non-malignant CNS lesions in HIV-infected patients

International Nuclear Information System (INIS)

Westwood, Thomas D.; Hogan, Celia; Julyan, Peter J.; Coutts, Glyn; Bonington, Suzie; Carrington, Bernadette; Taylor, Ben; Khoo, Saye; Bonington, Alec

2013-01-01

Background and purpose: In HIV infected patients, MRI cannot reliably differentiate between central nervous system (CNS) lymphoma and non-malignant CNS lesions, particularly cerebral toxoplasmosis (CTOX). This study prospectively investigates the utility of FDG PET-CT and magnetic resonance spectroscopy (MRS) in discriminating CNS lymphoma from non-malignant CNS lesions in HIV infected patients, and assesses the ability of FDG PET-CT to guide the use of early brain biopsy. Methods: 10 HIV patients with neurological symptoms and contrast enhancing lesions on MRI were commenced on anti-toxoplasmosis therapy before undergoing FDG PET-CT and MRS. Brain biopsies were sought in those with FDG PET-CT suggestive of CNS lymphoma, and in those with a negative FDG PET-CT scan who failed to respond to therapy. Final diagnosis was based on histology or treatment response. Results: Two patients were confirmed to have CNS lymphoma and FDG PET-CT was consistent with this diagnosis in both. Six patients had cerebral toxoplasmosis in all of whom FDG PET-CT was consistent with non-malignant disease. One patient had progressive multifocal leukoencephalopathy (PML), FDG PET-CT was equivocal. One patient had a haemorrhagic brain metastasis and FDG PET-CT wrongly suggested non-malignant disease. MRS was performed successfully in eight subjects: three results were suggestive of CNS lymphoma (one true positive, two false positive), four suggested CTOX (two false negative, two true negative), one scan was equivocal. Conclusion: FDG PET-CT correctly identified all cases of CNS lymphoma and CTOX, supporting its use in this situation. MRS was unhelpful in our cohort

Comparative antibiogram of coagulase-negative Staphylococci (CNS associated with subclinical and clinical mastitis in dairy cows

Directory of Open Access Journals (Sweden)

B. K. Bansal

2015-03-01

Full Text Available Aim: The present study was planned to determine the in vitro antibiotic susceptibility of coagulase-negative Staphylococci (CNS strains isolated from clinical and subclinical cases of mastitis in dairy cows. Antibiotic sensitivity profile will be helpful to recommend early therapy at the field level prior to availability of CST results. Materials and Methods: The milk samples from cases of clinical mastitis received in Mastitis Laboratory, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana and those of subclinical mastitis collected during routine screening of state dairy farms, were subjected to microbial culture. Identification of CNS organisms was done by standard biochemical tests. Antibiotic sensitivity testing, based on 30 antibiotics belonging to 12 groups, was done on 58 randomly selected CNS isolates (clinical isolates: 41, subclinical isolates: 17. Results: Isolates were highly susceptible to chloramphenicol (98.3%, gentamicin (93.1%, streptomycin (91.4%, linezolid (91.4%, ceftixozime (87.9%, cloxacillin (86.2%, clotrimazole (86.2%, bacitracin (86.2%, enrofloxacin (84.5% and ceftrioxone + tazobactum (70.7%, while resistance was observed against amoxicillin (77.6%, penicillin (75.9%, ampicillin (74.1% and cefoperazone (51.7%. Overall, isolates from clinical cases of mastitis had a higher resistance than subclinical isolates. Conclusion: CNS isolates were susceptible to chloramphenicol, gentamicin and streptomycin, while higher resistance was recorded against routinely used penicillin group.

Prophylactic CNS therapy in childhood leukemia

International Nuclear Information System (INIS)

Yokoyama, Takashi; Hiyoshi, Yasuhiko; Fujimoto, Takeo

1982-01-01

This study was designed to evaluate the efficacy of CNS-prophylaxis with high-dose methotrexate (MTX). Seventy children with previously untreated acute lymphoblastic leukemia (ALL) entered to this study between July 1978 and December 1980. According to initial white blood count (WBC), they were stratified to induce remission with; vincristine and prednine in low initial WBC ( lt 25,000/mm 3 ) group and these two agents plus adriamycin in high initial WBC ( gt 25,000/mm 3 ) group. After inducing remission, 62 children who achieved CR, received different CNS-prophlaxis; using a regimen of three doses of weekly high-dose MTX (1,000 mg/m 2 ) 6-hour infusion, which was repeated every 12 weeks-Group A (n = 14); high-dose MTX followed by 2400 rad cranial irradiation plus three doses of i.t. MT X-Group B (n = 15), 2400 rad cranial irradiation plus three doses of i.t. MTX-Group C (n = 16), and in 17 patients with high initial WBC, same as in Group A-Group D (n = 17). During an intravenous 6-h infusion of MTX at a dose of 1,000 mg/m 2 , the CSF concentration of MTX rose to 2.3 +- 2.4 x 10 -6 M after initiation of infusion and remained in 10 -7 M level for 48 hours. CNS-leukemia terminated complete remission in one of 14 children in Group A, two of 15 in Group B, two of 16 in Group C and two of 17 in Group D. The cumulative incidence of CNS-leukemia at 20 months calculated by the technique of Kaplan and Meier was 0% i n Group A, 18.1% in Group B, 7.1% in Group C and 50.8% in Group D. There was no statistical difference among Groups A, B and C. These data suggested that CNS-prophylaxis with high-dose intravenous MTX was effective as well as 2400 rad cranial irradiation plus three doses of i.t. MTX in childhood ALL with low initial WBC. (author)

Early Intervention for Borderline Personality Disorder: Psychodynamic Therapy in Adolescents.

Science.gov (United States)

Salzer, Simone; Cropp, Carola; Streeck-Fischer, Annette

2014-01-01

Borderline personality disorder (BPD) should be understood as a disorder of development (Streeck-Fischer 2008, 2013) that has its first manifestation in late childhood and adolescence. There are only few treatment studies of adolescents meeting the diagnostic criteria of borderline personality disorder, although early interventions for these patients are urgently needed (see Chanen & McCutcheon 2013). We examined the effectiveness of an inpatient psychodynamic therapy (PDT). Twenty-eight adolescents fulfilling the DSM-IV diagnostic criteria of borderline personality disorder were treated with psychodynamic therapy. The mean duration of treatment was 29.87 weeks (SD = 15.88). Outcomes were remission rates, GAF, GSI, SDQ, IIP and BPI scores. Assessments were made at admission and after treatment. Pre-post comparisons and comparisons with normative data were conducted. At the end of treatment 39.29% of the patients were remitted. We found significant improvements for the GAF, GSI, SDQ, IIP (all p0.001) and the BPI (p = 0.006). These clinically relevant improvements demonstrate the effectiveness of psychodynamic therapy in adolescents with borderline personality disorder and stress the usefulness of an early intervention for these patients.

Early Intervention for Children with Autism Spectrum Disorders in China: A Family Perspective

Science.gov (United States)

Su, Xueyun; Long, Toby; Chen, Lianjun; Fang, Junming

2013-01-01

Autism spectrum disorders (ASD) were first reported in China in 1982. Since then, autism and other related disorders have been recognized by both the public and professionals. The importance of early intervention for children with ASD is becoming more accepted throughout China. A survey was designed to investigate the status of early intervention…

Birth-Related Posttraumatic Stress Disorder: Implications for Early Intervention Services

Science.gov (United States)

Pizur-Barnekow, Kris; Doering, Jennifer J.; Willett, Marjorie; Ruminski, Christine; Spring, Molly

2014-01-01

The positive impact of healthy relationships on child development is widely accepted. A healthy relationship between mother and child is at risk when a mother experiences symptoms of birth-related posttraumatic stress disorder (PTSD). Mothers of children with special needs are at high risk for this disorder and early intervention (EI)…

Autoimmune process in CNS under Cs-137 inner irradiation

International Nuclear Information System (INIS)

Lisyany, N.I.; Liubich, L.D.

1996-01-01

Autoimmune hypothesis as to the development of radiation-induced brain injuries stands high among the concepts of the CNS post-radiation damage pathogenesis. To study the changes occurring in a living organism affected by a small-dose radiation due to incorporated radionuclides as well as to create adequate models are of critical importance in the post-Chernobyl period. The effects of chronic small-dose inner radiation on the development of autoimmune responses were evaluated by determining the level of the CNS proteins and protein-induced antibodies to the CNS components. (author)

Genetic pharmacotherapy as an early CNS drug development strategy: testing glutaminase inhibition for schizophrenia treatment in adult mice

Directory of Open Access Journals (Sweden)

Susana eMingote

2016-01-01

Full Text Available Genetic pharmacotherapy is an early drug development strategy for the identification of novel CNS targets in mouse models prior to the development of specific ligands. Here for the first time, we have implemented this strategy to address the potential therapeutic value of a glutamate-based pharmacotherapy for schizophrenia involving inhibition of the glutamate recycling enzyme phosphate-activated glutaminase. Mice constitutively heterozygous for GLS1, the gene encoding glutaminase, manifest a schizophrenia resilience phenotype, a key dimension of which is an attenuated locomotor response to propsychotic amphetamine challenge. If resilience is due to glutaminase deficiency in adulthood, then glutaminase inhibitors should have therapeutic potential. However, this has been difficult to test given the dearth of neuroactive glutaminase inhibitors. So, we used genetic pharmacotherapy to test the therapeutic potential of glutaminase inhibition. We specifically asked whether adult induction of GLS1 heterozygosity would attenuate amphetamine responsiveness. We generated conditional floxGLS1 mice and crossed them with global CAG ERT2 cre/+ mice to produce GLS1 iHET mice, susceptible to tamoxifen induction of GLS1 heterozygosity. One month after tamoxifen treatment of adult GLS1 iHET mice, we found a 50% reduction in GLS1 allelic abundance and glutaminase mRNA levels in the brain. While GLS1 iHET mice showed some recombination prior to tamoxifen, there was no impact on mRNA levels. We then asked whether induction of GLS heterozygosity would attenuate the locomotor response to propsychotic amphetamine challenge. Before tamoxifen, control and GLS1 iHET mice did not differ in their response to amphetamine. One month after tamoxifen treatment, amphetamine-induced hyperlocomotion was blocked in GLS1 iHET mice. The block was largely maintained after 5 months. Thus, a genetically induced glutaminase reduction — mimicking pharmacological inhibition — strongly

Role of resident CNS cell populations in HTLV-1-associated neuroinflammatory disease.

Science.gov (United States)

Lepoutre, Veronique; Jain, Pooja; Quann, Kevin; Wigdahl, Brian; Khan, Zafar K

2009-01-01

Human T cell leukemia virus type 1 (HTLV-1), the first human retrovirus discovered, is the etiologic agent for a number of disorders; the two most common pathologies include adult T cell leukemia (ATL) and a progressive demyelinating neuroinflammatory disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The neurologic dysfunction associated with HAM/TSP is a result of viral intrusion into the central nervous system (CNS) and the generation of a hyperstimulated host response within the peripheral and central nervous system that includes expanded populations of CD4+ and CD8+ T cells and proinflammatory cytokines/chemokines in the cerebrospinal fluid (CSF). This robust, yet detrimental immune response likely contributes to the death of myelin producing oligodendrocytes and degeneration of neuronal axons. The mechanisms of neurological degeneration in HAM/TSP have yet to be fully delineated in vivo and may involve the immunogenic properties of the HTLV-1 transactivator protein Tax. This comprehensive review characterizes the available knowledge to date concerning the effects of HTLV-1 on CNS resident cell populations with emphasis on both viral and host factors contributing to the genesis of HAM/TSP.

Evidence for an agitated-aggressive syndrome in early-onset psychosis correlated with antisocial personality disorder, forensic history, and substance use disorder.

Science.gov (United States)

Huber, Christian G; Hochstrasser, Lisa; Meister, Klara; Schimmelmann, Benno G; Lambert, Martin

2016-08-01

Agitation, aggression, and violence are increased in psychotic disorders. Additionally, an earlier age at onset may be associated with aggressive behavior. However, the relationship of age at onset, an agitated-aggressive syndrome as measured with the Positive And Negative Syndrome Scale for Schizophrenia - Excited Component (PANSS-EC), and its potential correlates in first-episode psychosis (FEP) has not been studied. This study assessed the association between age at onset, an agitated-aggressive syndrome, and its potential correlates in a prospective sample of 52 FEP patients with early-onset and adult-onset followed up for 12months. Twenty-six patients conformed to the criteria of early-onset psychosis. Early age at onset was associated with antisocial personality disorder (p=0.004; φc=0.39), a history of legal involvement (p=0.005; φc=0.39), and higher rates of lifetime substance use disorder (SUD; p=0.002; φc=0.42). Early-onset patients had significantly higher PANSS-EC scores over the course of observation (F(1,44.4)=5.39; p=0.025; d=0.656), but no significant group differences emerged for the remaining PANSS subscores. PANSS-EC scores were correlated positively with antisocial personality disorder and forensic history at 6weeks, 3months, 6months, and 12months, and with lifetime substance use disorder at 3months and 6months. Patients with early onset psychosis may have increased levels of agitation/aggressiveness, and, more likely, antisocial personality disorder, forensic history, and lifetime substance use disorder. These variables were linked to suicidality, aggressiveness, and involuntary treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Possible role of glial cells in the relationship between thyroid dysfunction and mental disorders

Directory of Open Access Journals (Sweden)

Mami eNoda

2015-06-01

Full Text Available It is widely accepted that there is a close relationship between the endocrine system and the central nervous system (CNS. Among hormones closely related to the nervous system, thyroid hormones (THs are critical for the development and function of the CNS; not only for neuronal cells but also for glial development and differentiation. Any impairment of TH supply to the developing CNS causes severe and irreversible changes in the overall architecture and function of human brain, leading to various neurological dysfunctions. In adult brain, impairment of THs, such as hypothyroidism and hyperthyroidism, can cause psychiatric disorders such as schizophrenia, bipolar disorder, anxiety and depression. Though hypothyroidism impairs synaptic transmission and plasticity, its effect on glial cells and cellular mechanisms are unknown. This mini-review article summarizes how THs are transported to the brain, metabolized in astrocytes and affect microglia and oligodendrocytes, showing an example of glioendocrine system. It may help to understand physiological and/or pathophysiological functions of THs in the CNS and how hypo- and hyper-thyroidism may cause mental disorders.

TLR3 deficiency renders astrocytes permissive to herpes simplex virus infection and facilitates establishment of CNS infection in mice

DEFF Research Database (Denmark)

Reinert, Line; Harder, Louis Andreas; Holm, Christian

2012-01-01

Herpes simplex viruses (HSVs) are highly prevalent neurotropic viruses. While they can replicate lytically in cells of the epithelial lineage, causing lesions on mucocutaneous surfaces, HSVs also establish latent infections in neurons, which act as reservoirs of virus for subsequent reactivation......, it is not known what cell type mediates the role of TLR3 in the immunological control of HSV, and it is not known whether TLR3 sensing occurs prior to or after CNS entry. Here, we show that in mice TLR3 provides early control of HSV-2 infection immediately after entry into the CNS by mediating type I IFN...... responses in astrocytes. Tlr3-/- mice were hypersusceptible to HSV-2 infection in the CNS after vaginal inoculation. HSV-2 exhibited broader neurotropism in Tlr3-/- mice than it did in WT mice, with astrocytes being most abundantly infected. Tlr3-/- mice did not exhibit a global defect in innate immune...

Borderline Personality Disorder in the perinatal period: early infant and maternal outcomes.

Science.gov (United States)

Blankley, Gaynor; Galbally, Megan; Snellen, Martien; Power, Josephine; Lewis, Andrew J

2015-12-01

This study examines pregnancy and early infant outcomes of pregnant women with a clinical diagnosis of Borderline Personality Disorder presenting for obstetric services to a major metropolitan maternity hospital in Victoria, Australia. A retrospective case review of pregnancy and early infant outcomes on 42 women who had been diagnosed with Borderline Personality Disorder via psychiatric assessment using DSM-IV-R criteria was undertaken. Outcomes were compared with a control group of 14,313 consisting of women and infants of non-affected women from the same hospital over the same period of time. Women presenting for obstetric services with a clinical diagnosis of Borderline Personality Disorder experienced considerable psychosocial impairment. They anticipated birth as traumatic and frequently requested early delivery. High comorbidity with substance abuse was found and high rates of referral to child protective services. Mothers with Borderline Personality Disorder were significantly more likely to have negative birth outcomes such as lowered Apgar scores, prematurity and special care nursery referral when compared with controls. These findings offer preliminary evidence to be considered by clinicians in developing treatments and services for the perinatal care of women with Borderline Personality Disorder and their infants. Further research is required in order to develop evidence informed clinical guidelines for the management of women with Borderline Personality Disorder and their infants. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Parental and Child Characteristics Related to Early-Onset Disordered Eating

DEFF Research Database (Denmark)

Larsen, Pernille Stemann; Strandberg-Larsen, Katrine; Micali, Nadia

2015-01-01

the following: higher body weight, previously reported disordered eating, body dissatisfaction, depression, parental disordered eating, and parental comments/concerns about child's weight and eating. The findings were inconsistent for sex, age, socioeconomic status, ethnicity, self-esteem/worth, and parental......-four studies fit these criteria. Most studies were based on community samples with a cross-sectional design. The included studies varied considerably in size, instruments used to assess early-onset disordered eating, and parental and child characteristics investigated. Important determinants included...

Autism Spectrum Disorder Updates – Relevant Information for Early Interventionists to Consider

Science.gov (United States)

Allen-Meares, Paula; MacDonald, Megan; McGee, Kristin

2016-01-01

Autism spectrum disorder (ASD) is a pervasive developmental disorder characterized by deficits in social communication skills as well as repetitive, restricted or stereotyped behaviors (1). Early interventionists are often found at the forefront of assessment, evaluation, and early intervention services for children with ASD. The role of an early intervention specialist may include assessing developmental history, providing group and individual counseling, working in partnership with families on home, school, and community environments, mobilizing school and community resources, and assisting in the development of positive early intervention strategies (2, 3). The commonality among these roles resides in the importance of providing up-to-date, relevant information to families and children. The purpose of this review is to provide pertinent up-to-date knowledge for early interventionists to help inform practice in working with individuals with ASD, including common behavioral models of intervention. PMID:27840812

Engineering progress of CNS concept in Hanaro

International Nuclear Information System (INIS)

Choi, C.O.; Park, K.N.; Park, S.H.

1997-01-01

The Korea Atomic Energy research Institute (KAERI) strives to provide utilizing facilities on and around the Hanaro reactor in order to activate advanced researches by neutron application. As one of the facilities to be installed, the conceptual design work of CNS was started in 1996 with a project schedule of 5 years so that its installation work can be finished by the year 2000. And the major engineering targets of this CNS facility are established for a minimum physical interference with the present facilities of the Hanaro, a reach-out of very-high-gain factors in the cold neutron flux, a simplicity of the maintenance of the facility, and a safety in the operation of the facility as well as the reactor. For the conceptual design of Hanaro CNS, the experience of utilization and production of cold neutron at WWR-M reactor Gatchina, Russia has been used with that of elaborations for PIK reactor in design for neutron guide systems and instruments. (author)

Conversion (dissociative) symptoms as a presenting feature in early onset bipolar disorder: a case series

OpenAIRE

Ghosal, Malay Kumar; Guha, Prathama; Sinha, Mausumi; Majumdar, Debabrata; Sengupta, Payel

2009-01-01

We present three cases of early onset bipolar disorder where dissociative (conversion) symptoms preceded the onset of mania. This case series underscores the significance of dissociative/conversion symptoms as an early atypical presentation in juvenile bipolar disorder.

Prediction of human CNS pharmacokinetics using a physiologically-based pharmacokinetic modeling approach

NARCIS (Netherlands)

Yamamoto, Yumi; Valitalo, Pyry A.; Wong, Yin Cheong; Huntjens, Dymphy R.; Proost, Johannes H.; Vermeulen, An; Krauwinkel, Walter; Beukers, Margot W.; Kokki, Hannu; Kokki, Merja; Danhof, Meindert; van Hasselt, Johan G. C.; de Lange, Elizabeth C. M.

2018-01-01

Knowledge of drug concentration-time profiles at the central nervous system (CNS) target-site is critically important for rational development of CNS targeted drugs. Our aim was to translate a recently published comprehensive CNS physiologically-based pharmacokinetic (PBPK) model from rat to human,

Applications of Genomic Sequencing in Pediatric CNS Tumors.

Science.gov (United States)

Bavle, Abhishek A; Lin, Frank Y; Parsons, D Williams

2016-05-01

Recent advances in genome-scale sequencing methods have resulted in a significant increase in our understanding of the biology of human cancers. When applied to pediatric central nervous system (CNS) tumors, these remarkable technological breakthroughs have facilitated the molecular characterization of multiple tumor types, provided new insights into the genetic basis of these cancers, and prompted innovative strategies that are changing the management paradigm in pediatric neuro-oncology. Genomic tests have begun to affect medical decision making in a number of ways, from delineating histopathologically similar tumor types into distinct molecular subgroups that correlate with clinical characteristics, to guiding the addition of novel therapeutic agents for patients with high-risk or poor-prognosis tumors, or alternatively, reducing treatment intensity for those with a favorable prognosis. Genomic sequencing has also had a significant impact on translational research strategies in pediatric CNS tumors, resulting in wide-ranging applications that have the potential to direct the rational preclinical screening of novel therapeutic agents, shed light on tumor heterogeneity and evolution, and highlight differences (or similarities) between pediatric and adult CNS tumors. Finally, in addition to allowing the identification of somatic (tumor-specific) mutations, the analysis of patient-matched constitutional (germline) DNA has facilitated the detection of pathogenic germline alterations in cancer genes in patients with CNS tumors, with critical implications for genetic counseling and tumor surveillance strategies for children with familial predisposition syndromes. As our understanding of the molecular landscape of pediatric CNS tumors continues to advance, innovative applications of genomic sequencing hold significant promise for further improving the care of children with these cancers.

Early stages of bipolar disorder: characterization and strategies for early intervention

Directory of Open Access Journals (Sweden)

Adiel C. Rios

2015-12-01

Full Text Available Objective: To characterize the early stages of bipolar disorder (BD, defined as the clinical prodrome/subsyndromal stage and first-episode phase, and strategies for their respective treatment. Methods: A selective literature search of the PubMed, Embase, PsycINFO, and ISI databases from inception until March 2014 was performed. Included in this review were articles that a characterized prodromal and first-episode stages of BD or b detailed efficacy and safety/tolerability of interventions in patients considered prodromal for BD or those with only one episode of mania/hypomania. Results: As research has only recently focused on characterization of the early phase of BD, there is little evidence for the effectiveness of any treatment option in the early phase of BD. Case management; individual, group, and family therapy; supportive therapy; and group psychoeducation programs have been proposed. Most evidence-based treatment guidelines for BD do not address treatment specifically in the context of the early stages of illness. Evidence for pharmacotherapy is usually presented in relation to illness polarity (i.e., manic/mixed or depressed or treatment phase. Conclusions: Although early recognition and treatment are critical to preventing unfavorable outcomes, there is currently little evidence for interventions in these stages of BD.

Therapy of CNS leukemia with intraventricular chemotherapy and low-dose neuraxis radiotherapy

International Nuclear Information System (INIS)

Steinherz, P.; Jereb, B.; Galicich, J.

1985-01-01

Successful treatment of CNS leukemic relapse has been frustrated by frequent local recurrence and eventual marrow relapse. The authors describe the treatment of meningeal leukemia in 39 children with intrathecal remission induction followed by the placement of an Ommaya reservoir to facilitate the administration and distribution of chemotherapeutic agents into the CSF. Six hundred or 900 rad of craniospinal radiation and maintenance intraventricular and intrathecal chemotherapy was then administered. Systemic reinduction therapy was added in the later cases. Sixteen children (41%) experienced no further events, with 17+ months to 13+ years (median, 25 months) follow-up . Eleven patients (28%) had CNS recurrence, nine (23%) bone marrow (BM) relapse, and two (5%) testicular relapse as the next adverse event. The course of patients with first isolated CNS relapse differed from that of the others. Eleven (69%) of 16 patients treated for first isolated CNS relapse are alive and 9 are event free, while only 35% of patients whose CNS relapse occurred simultaneously or after recurrent disease at other sites are alive (P = .04). Seven of 23 in the later group are event free. The difference is due to the increased incidence of BM relapse in the later group (30% v 6%; P = .04). For patients with first isolated CNS relapse, the life-table median CNS remission duration is 42 months. The projected CNS relapse-free survival and event-free survival 8 to 10 years after CNS relapse are 40% and 32%, respectively. Headache, nausea, and emesis of short duration were frequent during therapy. In three patients, the reservoir had to be removed for infection. No patient suffered neurologic deficit related to the reservoir. The therapy described can reduce the CNS relapse rate with manageable toxicity

Early developmental characteristics and features of major depressive disorder among child psychiatric patients in Hungary.

Science.gov (United States)

Kapornai, Krisztina; Gentzler, Amy L; Tepper, Ping; Kiss, Eniko; Mayer, László; Tamás, Zsuzsanna; Kovacs, Maria; Vetró, Agnes

2007-06-01

We investigate the relations of early atypical characteristics (perinatal problems, developmental delay, and difficult temperament) and onset-age (as well as severity of) first major depressive disorder (MDD) and first internalizing disorder in a clinical sample of depressed children in Hungary. Participants were 371 children (ages 7-14) with MDD, and their biological mothers, recruited through multiple clinical sites. Diagnoses (via DSM-IV criteria) and onset dates of disorders were finalized "best estimate" psychiatrists, and based on multiple information sources. Mothers provided developmental data in a structured interview. Difficult temperament predicted earlier onset of MDD and first internalizing disorder, but its effect was ameliorated if the family was intact during early childhood. Further, the importance of difficult temperament decreased as a function of time. Perinatal problems and developmental delay did not impact onset ages of disorders, and none of the early childhood characteristics associated with MDD episode severity. Children with MDD may have added disadvantage of earlier onset if they had a difficult temperament in infancy. Because early temperament mirrors physiological reactivity and regulatory capacity, it can affect various areas of functioning related to psychopathology. Early caregiver stability may attenuate some adverse effects of difficult infant temperament.

Assessing Early Communication Skills at 12 Months: A Retrospective Study of Autism Spectrum Disorder

Science.gov (United States)

Swain, Nathaniel Robert; Eadie, Patricia Ann; Prior, Margot Ruth; Reilly, Sheena

2015-01-01

Background: Early identification of Autism Spectrum Disorder (ASD) is currently limited by the absence of reliable biological markers for the disorder, as well as the reliability of screening and assessment tools for children aged between 6 and 18 months. Ongoing research has demonstrated the importance of early social communication skills in…

Gut-derived factors promote neurogenesis of CNS-neural stem cells and nudge their differentiation to an enteric-like neuronal phenotype.

Science.gov (United States)

Kulkarni, Subhash; Zou, Bende; Hanson, Jesse; Micci, Maria-Adelaide; Tiwari, Gunjan; Becker, Laren; Kaiser, Martin; Xie, Xinmin Simon; Pasricha, Pankaj Jay

2011-10-01

Recent studies have explored the potential of central nervous system-derived neural stem cells (CNS-NSC) to repopulate the enteric nervous system. However, the exact phenotypic fate of gut-transplanted CNS-NSC has not been characterized. The aim of this study was to investigate the effect of the gut microenvironment on phenotypic fate of CNS-NSC in vitro. With the use of Transwell culture, differentiation of mouse embryonic CNS-NSC was studied when cocultured without direct contact with mouse intestinal longitudinal muscle-myenteric plexus preparations (LM-MP) compared with control noncocultured cells, in a differentiating medium. Differentiated cells were analyzed by immunocytochemistry and quantitative RT-PCR to assess the expression of specific markers and by whole cell patch-clamp studies for functional characterization of their phenotype. We found that LM-MP cocultured cells had a significant increase in the numbers of cells that were immune reactive against the panneuronal marker β-tubulin, neurotransmitters neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), and neuropeptide vasoactive intestinal peptide (VIP) and showed an increase in expression of these genes, compared with control cells. Whole cell patch-clamp analysis showed that coculture with LM-MP decreases cell excitability and reduces voltage-gated Na(+) currents but significantly enhances A-current and late afterhyperpolarization (AHP) and increases the expression of the four AHP-generating Ca(2+)-dependent K(+) channel genes (KCNN), compared with control cells. In a separate experiment, differentiation of LM-MP cocultured CNS-NSC produced a significant increase in the numbers of cells that were immune reactive against the neurotransmitters nNOS, ChAT, and the neuropeptide VIP compared with CNS-NSC differentiated similarly in the presence of neonatal brain tissue. Our results show that the gut microenvironment induces CNS-NSC to produce neurons that share some of the

[Integrative parent-infant psychotherapy for early regulatory and relationship disorders].

Science.gov (United States)

Papousek, Mechthild; de Chuquisengo, Ruth Wollwerth

2006-01-01

The author introduces both the concept and practice of Integrative Parent-Infant Psychotherapy (IPI-P), a treatment specifically designed for the most frequent developmental problems and psychological needs of infants and their parents. Based on growing knowledge from interdisciplinary infancy research, both basic and clinical, IPI-P has been developed and practised in the "Munich Interdisciplinary Research and Intervention Program" for early regulatory and relationship disorders since the early nineties. Preverbal parent-infant communication represents both the port of entry into the system and the main focus of diagnostics, developmental counselling, interaction guidance, or psychodynamic psychotherapy of distorted communication and distressed/disordered relationships. The method of videomicroanalysis during video-feedback with the parent has proven particularly efficient--while observing, reliving and working through brief episodes of recorded parent-infant interaction. The author illustrates the diagnostic and therapeutic procedures with excerpts from psychotherapy of a toddler with an age-specific regulatory disorder in the context of severely distressed primary relationships.

Kindling of Life Stress in Bipolar Disorder: Effects of Early Adversity.

Science.gov (United States)

Shapero, Benjamin G; Weiss, Rachel B; Burke, Taylor A; Boland, Elaine M; Abramson, Lyn Y; Alloy, Lauren B

2017-05-01

Most theoretical frameworks regarding the role of life stress in bipolar disorders (BD) do not incorporate the possibility of a changing relationship between psychosocial context and episode initiation across the course of the disorder. The kindling hypothesis theorizes that over the longitudinal course of recurrent affective disorders, the relationship between major life stressors and episode initiation declines (Post, 1992). The present study aimed to test an extension of the kindling hypothesis in BD by examining the effect of early life adversity on the relationship between proximal life events and prospectively assessed mood episodes. Data from 145 bipolar participants (59.3% female, 75.2% Caucasian, and mean age of 20.19 years; SD = 1.75 years) were collected as part of the Temple-Wisconsin Longitudinal Investigation of Bipolar Spectrum Project (112 Bipolar II; 33 Cyclothymic disorder). Participants completed a self-report measure of early adversity at baseline and interview-assessed mood episodes and life events at regular 4-month follow-ups. Results indicate that early childhood adversity sensitized bipolar participants to the effects of recent stressors only for depressive episodes and not hypomanic episodes within BD. This was particularly the case with minor negative events. The current study extends prior research examining the kindling model in BD using a methodologically rigorous assessment of life stressors and mood episode occurrence. Clinicians should assess experiences of early adversity in individuals with BD as it may impact reactivity to developing depressive episodes in response to future stressors. Copyright © 2017. Published by Elsevier Ltd.

HMGB1/anti-HMGB1 antibodies define a molecular signature of early stages of HIV-Associated Neurocognitive Isorders (HAND

Directory of Open Access Journals (Sweden)

Marie-Lise Gougeon

2017-02-01

Conclusion: We report that brain injury in chronically HIV-infected patients on stable HAART is strongly associated with persistent CNS inflammation, which is correlated with increased levels of HMGB1 and anti-HMGB1 IgG in the CSF. Moreover, we identified circulating anti-HMGB1 IgG as a very early biomarker of neurological impairment in patients without HAND. These results might have important implication for the identification of patients who are at high risk of developing neurological disorders.

Eating disorders in persons with type 1 diabetes: A focus group investigation of early eating disorder risk.

Science.gov (United States)

Powers, Margaret A; Richter, Sara A; Ackard, Diann M; Cronemeyer, Catherine

2016-12-01

Through focus groups, we examined the development and maintenance of an eating disorder in 16 females with type 1 diabetes and an eating disorder. The quotes and qualitative data summaries provide rich insights into understanding why those with type 1 diabetes are at increased risk for eating disorders. Content analyses revealed five themes pertinent to the dual diagnosis (feeling different, difficulty with control/coping, body image, feelings, and quality of life) of which four themes were relevant to eating disorder development. Findings support early identification of those at risk and inform interventions to mitigate development of an eating disorder. © The Author(s) 2015.

Autism spectrum disorder updates – relevant information for early interventionists to consider

Directory of Open Access Journals (Sweden)

Paula Allen-Meares

2016-10-01

Full Text Available Autism spectrum disorder (ASD is a pervasive developmental disorder characterized by deficits in social communication skills as well as repetitive, restricted or stereotyped behaviors (1. Early interventionists are often found at the forefront of assessment, evaluation and early intervention services for children with ASD. The role of an early intervention specialist may include, assessing developmental history, providing group and individual counseling, working in partnership with families on home, school, and community environments, mobilizing school and community resources and assisting in the development of positive early intervention strategies (2, 3. The commonality amongst these roles resides in the importance of providing up-to-date, relevant information to families and children. The purpose of this review is to provide pertinent up-to-date knowledge for early interventionists to help inform practice in working with individuals with ASD, including common behavioral models of intervention.

Developmentally sensitive diagnostic criteria for mental health disorders in early childhood: the diagnostic and statistical manual of mental disorders-IV, the research diagnostic criteria-preschool age, and the diagnostic classification of mental health and developmental disorders of infancy and early childhood-revised.

Science.gov (United States)

Egger, Helen L; Emde, Robert N

2011-01-01

As the infant mental health field has turned its focus to the presentation, course, and treatment of clinically significant mental health disorders, the need for reliable and valid criteria for identifying and assessing mental health symptoms and disorders in early childhood has become urgent. In this article we offer a critical perspective on diagnostic classification of mental health disorders in young children. We place the issue of early childhood diagnosis within the context of classification of psychopathology at other ages and describe, in some detail, diagnostic classifications that have been developed specifically for young children, including the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC:0-3R; ZERO TO THREE, 2005), a diagnostic classification for mental health symptoms and disorders in infants, toddlers, and preschoolers. We briefly outline the role of diagnostic classification in clinical assessment and treatment planning. Last, we review the limitations of current approaches to the diagnostic classification of mental health disorders in young children. PsycINFO Database Record (c) 2010 APA, all rights reserved.

Investigating autism spectrum disorder and autistic traits in early onset eating disorder.

Science.gov (United States)

Pooni, Jyoti; Ninteman, Aafke; Bryant-Waugh, Rachel; Nicholls, Dasha; Mandy, William

2012-05-01

To investigate whether young people (8-16 years) with an eating disorder have a higher prevalence of autism spectrum disorder (ASDs) and elevated autistic traits compared to typically developing (TD) peers. Twenty-two participants with early onset eating disorder (EOED) were assessed using standardized ASD measures and compared to IQ matched TD (n = 24) and ASD (n = 20) controls. An ASD diagnosis was no more common in EOED than in TD controls. However, repetitive and stereotyped behavior was more often observed in the EOED group and, compared to TD controls, there was a trend (p = .07) toward greater autistic social impairment in EOED. Whilst participants with EOED did not show increased ASD prevalence, they did have elevated autistic traits of clinical significance, particularly repetitive and stereotyped behavior. Further work is required to determine whether inflexibility and social difficulties in EOED have identical phenomenology and etiology to those seen in ASD. Copyright © 2012 Wiley Periodicals, Inc.

Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals

Directory of Open Access Journals (Sweden)

Jacinta Nwamaka Nwogu

2016-01-01

Full Text Available Neurological complications associated with the human immunodeficiency virus (HIV are a matter of great concern. While antiretroviral (ARV drugs are the cornerstone of HIV treatment and typically produce neurological benefit, some ARV drugs have limited CNS penetration while others have been associated with neurotoxicity. CNS penetration is a function of several factors including sieving role of blood-brain and blood-CSF barriers and activity of innate drug transporters. Other factors are related to pharmacokinetics and pharmacogenetics of the specific ARV agent or mediated by drug interactions, local inflammation, and blood flow. In this review, we provide an overview of the various factors influencing CNS penetration of ARV drugs with an emphasis on those commonly used in sub-Saharan Africa. We also summarize some key associations between ARV drug penetration, CNS efficacy, and neurotoxicity.

Association of Tic Disorders and Enterovirus Infection

Science.gov (United States)

Tsai, Ching-Shu; Yang, Yao-Hsu; Huang, Kuo-You; Lee, Yena; McIntyre, Roger S.; Chen, Vincent Chin-Hung

2016-01-01

Abstract There has been growing interest in the association between infectious disease and mental disorders, but an association between enterovirus (EV) infection and tic disorders has not been sufficiently explored. Herein, we aim to investigate the association between EV infection and incidence of tic disorders in a nationwide population-based sample using Taiwan's National Health Insurance Research Database. We identified individuals aged ≤18 years prior to 2005 with an inpatient diagnosis of EV infection and/or history of EV infection. Tic disorder was operationalized using International Classification of Disease, Revision 9, Clinical Modification (ICD-9-CM) codes 307.20–307.23. A total of 47,998 individuals with history of EV infection were compared to 47,998 sex-, age-, and urbanization-matched controls on incidence of tic disorders. The mean ± standard deviation follow-up period for all subjects was 9.7 ± 3.6 years; the mean latency period between initial EV infection and incident diagnosis of tic disorder diagnosis was 5.4 ± 2.8 years. EV infection was significantly associated with greater incidence of tic disorders (hazard ratio [HR] = 1.24, 95% CI: 1.07–1.45). When subgrouped on the basis of central nervous system (CNS) involvement, EV infection with CNS involvement was not significantly associated with greater incidence of tic disorders when compared to controls (HR = 1.25, 95% CI: 0.64–2.43); EV infection without CNS involvement was significantly associated greater incidence of tic disorders when compared to controls (HR = 1.24, 95% CI: 1.07–1.45). In addition, hospitalization for an EV infection did not increase the hazard for greater incidence of tic disorders (HR = 1.32, 95% CI: 1.04–1.67 with hospitalization and 1.22, 95% CI: 1.04–1.44 without hospitalization). EV infection is temporally associated with incidence of tic disorders. Our observations add to the growing body of literature implicating immune

Early behavioral intervention, brain plasticity, and the prevention of autism spectrum disorder.

Science.gov (United States)

Dawson, Geraldine

2008-01-01

Advances in the fields of cognitive and affective developmental neuroscience, developmental psychopathology, neurobiology, genetics, and applied behavior analysis have contributed to a more optimistic outcome for individuals with autism spectrum disorder (ASD). These advances have led to new methods for early detection and more effective treatments. For the first time, prevention of ASD is plausible. Prevention will entail detecting infants at risk before the full syndrome is present and implementing treatments designed to alter the course of early behavioral and brain development. This article describes a developmental model of risk, risk processes, symptom emergence, and adaptation in ASD that offers a framework for understanding early brain plasticity in ASD and its role in prevention of the disorder.

Shared genetic and environmental influences on early temperament and preschool psychiatric disorders in Hispanic twins.

Science.gov (United States)

Silberg, Judy L; Gillespie, Nathan; Moore, Ashlee A; Eaves, Lindon J; Bates, John; Aggen, Steven; Pfister, Elizabeth; Canino, Glorisa

2015-04-01

Despite an increasing recognition that psychiatric disorders can be diagnosed as early as preschool, little is known how early genetic and environmental risk factors contribute to the development of psychiatric disorders during this very early period of development. We assessed infant temperament at age 1, and attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and separation anxiety disorder (SAD) at ages 3 through 5 years in a sample of Hispanic twins. Genetic, shared, and non-shared environmental effects were estimated for each temperamental construct and psychiatric disorder using the statistical program MX. Multivariate genetic models were fitted to determine whether the same or different sets of genes and environments account for the co-occurrence between early temperament and preschool psychiatric disorders. Additive genetic factors accounted for 61% of the variance in ADHD, 21% in ODD, and 28% in SAD. Shared environmental factors accounted for 34% of the variance in ODD and 15% of SAD. The genetic influence on difficult temperament was significantly associated with preschool ADHD, SAD, and ODD. The association between ODD and SAD was due to both genetic and family environmental factors. The temperamental trait of resistance to control was entirely accounted for by the shared family environment. There are different genetic and family environmental pathways between infant temperament and psychiatric diagnoses in this sample of Puerto Rican preschool age children.

Genetic models for CNS inflammation

DEFF Research Database (Denmark)

Owens, T; Wekerle, H; Antel, J

2001-01-01

The use of transgenic technology to over-express or prevent expression of genes encoding molecules related to inflammation has allowed direct examination of their role in experimental disease. This article reviews transgenic and knockout models of CNS demyelinating disease, focusing primarily on ...

School Age Outcomes of Children Diagnosed Early and Later with Autism Spectrum Disorder

Science.gov (United States)

Clark, Megan Louise Erin; Vinen, Zoe; Barbaro, Josephine; Dissanayake, Cheryl

2018-01-01

Early diagnosis of Autism Spectrum Disorder is considered best practice, increasing access to early intervention. Yet, many children are diagnosed after 3-years. The current study investigated the school age outcomes of children who received an early and later diagnosis of ASD. The cognitive and behavioural outcomes of children diagnosed early (n…

Manic depressive psychosis and schizophrenia are neurological disorders at the extremes of CNS maturation and nutritional disorders associated with a deficit in marine fat.

Science.gov (United States)

Saugstad, L F

2001-12-01

The maturational theory of brain development comprises manic depressive psychosis and schizophrenia. It holds that the disorders are part of human diversity in growth and maturation, which explains their ubiquity, shared susceptibility genes and multifactorial inheritance. Rate of maturation and age at puberty are the genotype; the disorders are localized at the extremes with normality in between. This is based on the association between onset of puberty and the final regressive event, with pruning of 40% of excitatory synapses leaving the inhibitory ones fairly unchanged. This makes excitability, a fundamental property of nervous tissue, a distinguishing factor: the earlier puberty, the greater excitability--the later puberty, the greater deficit. Biological treatment supports deviation from the norm: neuroleptics are convulsant; antidepressives are anti-epiletogenic. There is an association between onset of puberty and body-build: early maturers are pyknic broad-built, late ones linearly leptosomic. This discrepancy is similar to that in the two disorders, supporting the theory that body-build is the phenotype. Standard of living is the environmental factor, which affects pubertal age and shifts the panorama of mental illness accordingly. Unnatural death has increased with antipsychotics. Other treatment is needed. PUFA deficit has been observed in RBC in both disorders and striking improvements with addition of minor amounts of PUFA. This supports that dietary deficit might cause psychotic development and that prevention is possible. Other neurological disorders also profit from PUFA, underlining a general deficit in the diet.

Early diagnosis of junior school age children’s posture disorders

Directory of Open Access Journals (Sweden)

N.S. Razumeiko

2015-12-01

Full Text Available Purpose: to describe specificities of early diagnosis method for junior school age children’s posture disorders. Material: in pedagogic experiment 156 junior school age children (boys and girls of 7-10 years’ age participated. All children had no experience of training in sport circles. For determination of uniformity of the tested we fulfilled experts’ examination for presence or absence of external signs of posture disorders in frontal plane. The children’s examination was conducted by qualified specialists at the beginning and at the end of experiment. For determination of early signs of muscular asymmetry in torso right and left sides of the tested children we used methodic, based on registration of tonic vibration reflex. Results: the pupils’ examination permitted to form a group of 108 persons, who did not have external signs of posture disorders. It was proved that it would be purposeful to take prophylaxis measures at very early stages of imbalance in muscular system’s work. Traditional approach in the form of prophylaxis examination can not give confident information about initial stage of imbalance in muscular system’s work in child’s organism. Conclusions: it was found that imbalance of motor nervous centers reflex excitability on both sides of backbone (if no purposeful prophylaxis measures are taken can result in muscular tonus asymmetry on right and left sides of torso in lumbar spine area.

A Rare Case of Neuromyelitis Optica Spectrum Disorder in Patient with Sjogren’s Syndrome

Directory of Open Access Journals (Sweden)

Supat Thongpooswan

2014-01-01

Full Text Available We report a 48-year-old female with the history of Sjogren’s syndrome who presented with 3-week history of tingling, numbness, and shooting back, waist, and bilateral leg pain and numbness in the pelvic region with urinary and bowel incontinence. Physical examination was remarkable for reduced motor power in both lower extremities with spasticity. Sensory deficit was noted at the T6 level. Laboratory investigation revealed elevated ESR and CRP and positive serum antiaquaporin-4 IgG. Thoracic and lumbar magnetic resonance imaging revealed abnormal patchy areas, leptomeningeal enhancement through the thoracic cord extending from T3 through T6 levels, without evidence of cord compression. Impression of neuromyelitis optica spectrum disorder was made and patient was treated with methylprednisolone intravenously followed by tapering oral prednisone. Neurological symptoms gradually improved with resolution of bowel and urinary incontinence. In a patient with Sjogren’s syndrome who presents with neurological complaints, the possibility of neuromyelitis optica or neuromyelitis optica spectrum disorder should be considered. Awareness of the possibility of CNS disease is important due to the serious nature of CNS complications, some of which are treatable with immunosuppressants. Our patient with Sjogren’s syndrome who presented with myelopathy benefited from early recognition and institution of appropriate therapy.

Actuarial risk of isolated CNS involvement in Ewing's sarcoma following prophylactic cranial irradiation and intrathecal methotrexate

International Nuclear Information System (INIS)

Trigg, M.E.; Makuch, R.; Glaubiger, D.

1985-01-01

Records of 154 patients with Ewing's sarcoma treated at the National Cancer Institute were reviewed to assess the incidence and risk of developing isolated central nervous system (CNS) Ewing's sarcoma. Sixty-two of the 154 patients had received CNS irradiation and intrathecal (i.t.) methotrexate as part of their initial therapy to prevent the occurrence of isolated CNS Ewing's sarcoma. The risk of developing isolate CNS Ewing's sarcoma was greatest within the first two years after diagnosis and was approximately 10%. The overall risk of CNS recurrence in the group of patients receiving DNS treatment was similar to the group receiving no therapy directed to the CNS. The occurrence of isolated CNS involvement was not prevented by the use of CNS irradiation and i.t. methotrexate. Because of a lack of efficacy to the CNS irradiation regimen, current treatment regimens do not include therapy directed to CNS

Can injured adult CNS axons regenerate by recapitulating development?

Science.gov (United States)

Hilton, Brett J; Bradke, Frank

2017-10-01

In the adult mammalian central nervous system (CNS), neurons typically fail to regenerate their axons after injury. During development, by contrast, neurons extend axons effectively. A variety of intracellular mechanisms mediate this difference, including changes in gene expression, the ability to form a growth cone, differences in mitochondrial function/axonal transport and the efficacy of synaptic transmission. In turn, these intracellular processes are linked to extracellular differences between the developing and adult CNS. During development, the extracellular environment directs axon growth and circuit formation. In adulthood, by contrast, extracellular factors, such as myelin and the extracellular matrix, restrict axon growth. Here, we discuss whether the reactivation of developmental processes can elicit axon regeneration in the injured CNS. © 2017. Published by The Company of Biologists Ltd.

Do Early Caregiver Concerns Differ for Girls with Autism Spectrum Disorders?

Science.gov (United States)

Little, Lauren M.; Wallisch, Anna; Salley, Brenda; Jamison, Rene

2017-01-01

Given that early caregiver concerns may be different for children who go on to receive a diagnosis of autism spectrum disorder versus another developmental disability, early caregiver concerns may differ for girls. Using a community-based sample of children (n = 241), we examined the extent to which gender differences may be related to caregiver…

Netrin-1 Confines Rhombic Lip-Derived Neurons to the CNS

Directory of Open Access Journals (Sweden)

Andrea R. Yung

2018-02-01

Full Text Available During brainstem development, newborn neurons originating from the rhombic lip embark on exceptionally long migrations to generate nuclei important for audition, movement, and respiration. Along the way, this highly motile population passes several cranial nerves yet remains confined to the CNS. We found that Ntn1 accumulates beneath the pial surface separating the CNS from the PNS, with gaps at nerve entry sites. In mice null for Ntn1 or its receptor DCC, hindbrain neurons enter cranial nerves and migrate into the periphery. CNS neurons also escape when Ntn1 is selectively lost from the sub-pial region (SPR, and conversely, expression of Ntn1 throughout the mutant hindbrain can prevent their departure. These findings identify a permissive role for Ntn1 in maintaining the CNS-PNS boundary. We propose that Ntn1 confines rhombic lip-derived neurons by providing a preferred substrate for tangentially migrating neurons in the SPR, preventing their entry into nerve roots.

Treatment of HIV in the CNS: effects of antiretroviral therapy and the promise of non-antiretroviral therapeutics.

Science.gov (United States)

Peluso, Michael J; Spudich, Serena

2014-09-01

The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.

Affective spectrum disorders and role of serotonergic system of the brain

Directory of Open Access Journals (Sweden)

Timotijević Ivana P.

2014-01-01

Full Text Available Affective spectrum disorders include mood and anxiety disorders, whereas the term functional somatic syndromes describes disorders in which the main symptom is chronic pain, with no pathognomonic tissue damage, such as fibromyalgia, irritable colon, tension headache. Pain as a symptom is often present in patients with depression and anxiety, and similarly, depressed mood, anxiety and other psychiatric symptoms are common in patients with functional somatic syndromes. This explains attitudes that affective disorders and functional somatic syndromes should be found along the same spectrum, due to a similar neurobiochemicalmehanism and dysfunction of these CNS structures and neurotransmitter systems, which lead to similar symptoms in both groups. The symptoms of affective disorders, including somatic are associated with serotonin and serotonergic transmission in the CNS. The existence of depressive and anxiety disorders, such as fatigue, sleep disorders, cognitive disorders, depressed mood, anxiety, and functional somatic syndromes code indicate a similar mechanism of origin. Hypothesis of central neuropathic pain explains the possibility of the descending inhibitory pain mechanisms, including serotonergic and noradrenergic projections and their receptors. Central suprasegmental senzitization in nociceptive pathways, also at the level of the thalamus and the sensory cortex, trigered by an emotional stressors can cause painful symptoms in both groups of disorders. Serotonergic and noradrenergic pathways and voltage sensitive channels of their receptors are included in the mechanism. Modern psychopharmacology can no longer ignore the existence of painful symptoms in affective disorder or depressive and anxiety symptoms in functional somatic syndromes and their treatment can improve. Therapeutic effects of SSRI and SNRI antidepressants and alpha 2 delta ligands for all kinds of painful symptoms in affective disorders - serotonergic spectrum is

CNS complications of rotavirus gastroenteritis

International Nuclear Information System (INIS)

Volosinova, D.

2010-01-01

Rotavirus infection may be accompanied by serious complications, e.g. disabilities central nervous system (CNS). Theory rotavirus penetration across the blood-brain barrier and subsequent rota-associated convulsions by the 2-year case-history of the patient. Rotavirosis minor gastrointestinal symptoms may lead to erroneous diagnosis. (author)

CNS Involvement in AML Patient Treated with 5-Azacytidine

Directory of Open Access Journals (Sweden)

Diamantina Vasilatou

2014-01-01

Full Text Available Central nervous system (CNS involvement in acute myeloid leukemia (AML is a rare complication of the disease and is associated with poor prognosis. Sometimes the clinical presentation can be unspecific and the diagnosis can be very challenging. Here we report a case of CNS infiltration in a patient suffering from AML who presented with normal complete blood count and altered mental status.

Differential expression of metallothioneins in the CNS of mice with experimental autoimmune encephalomyelitis

DEFF Research Database (Denmark)

Espejo, C; Carrasco, J; Hidalgo, J

2001-01-01

Multiple sclerosis is an inflammatory, demyelinating disease of the CNS. Metallothioneins-I+II are antioxidant proteins induced in the CNS by immobilisation stress, trauma or degenerative diseases which have been postulated to play a neuroprotective role, while the CNS isoform metallothionein......-III has been related to Alzheimer's disease. We have analysed metallothioneins-I-III expression in the CNS of mice with experimental autoimmune encephalomyelitis. Moreover, we have examined the putative role of interferon-gamma, a pro-inflammatory cytokine, in the control of metallothioneins expression...

Early diagnosis of junior school age children’s posture disorders

OpenAIRE

N.S. Razumeiko

2015-01-01

Purpose: to describe specificities of early diagnosis method for junior school age children’s posture disorders. Material: in pedagogic experiment 156 junior school age children (boys and girls of 7-10 years’ age) participated. All children had no experience of training in sport circles. For determination of uniformity of the tested we fulfilled experts’ examination for presence or absence of external signs of posture disorders in frontal plane. The children’s examination was conducted by qua...

Comparative antibiogram of coagulase-negative Staphylococci (CNS) associated with subclinical and clinical mastitis in dairy cows

OpenAIRE

B. K. Bansal; D. K. Gupta; T. A. Shafi; S. Sharma

2015-01-01

Aim: The present study was planned to determine the in vitro antibiotic susceptibility of coagulase-negative Staphylococci (CNS) strains isolated from clinical and subclinical cases of mastitis in dairy cows. Antibiotic sensitivity profile will be helpful to recommend early therapy at the field level prior to availability of CST results. Materials and Methods: The milk samples from cases of clinical mastitis received in Mastitis Laboratory, Guru Angad Dev Veterinary and Animal Sciences Univer...

Early adolescent substance use as a risk factor for developing conduct disorder and depression symptoms.

Science.gov (United States)

Wymbs, Brian T; McCarty, Carolyn A; Mason, W Alex; King, Kevin M; Baer, John S; Vander Stoep, Ann; McCauley, Elizabeth

2014-03-01

Conduct disorder and depression symptoms are well-established risk factors for substance use during adolescence. However, few investigations have examined whether early substance use increases adolescents' risk of developing conduct disorder/depression symptoms. Using the Developmental Pathways Project sample of 521 middle school students (51.6% male), we tested whether substance use (indicated by alcohol and marijuana use, and use-related impairment) in 8th and 9th grade increased risk of conduct disorder and depression symptoms in 9th and 12th grade over and above prior symptoms. We examined whether associations between substance use and conduct disorder/depression symptoms were consistent across self- or parent-reported symptoms and whether associations were moderated by gender. Analyses indicated that, over and above prior symptoms, elevated substance use in 8th grade predicted elevated conduct disorder symptoms in 9th grade, and substance use in 9th grade predicted conduct disorder symptoms in 12th grade. In contrast, substance use failed to predict later depression symptoms independent of prior symptoms. These findings were consistent across self- and parent-reported conduct disorder/depression symptoms. With one exception (association between substance use in 8th grade and self-reported conduct disorder symptoms in 9th grade), relations between early substance use and later conduct disorder symptoms did not differ between boys and girls. Study findings underscore the unique contribution of substance use during early adolescence to the development of conduct disorder symptoms by late adolescence.

The gut microbiota and its correlations with the central nervous system disorders.

Science.gov (United States)

Catanzaro, R; Anzalone, M; Calabrese, F; Milazzo, M; Capuana, M; Italia, A; Occhipinti, S; Marotta, F

2015-09-01

A mutual impact of gastrointestinal tract (GIT) and central nervous system (CNS) functions has been recognized since the mid-twentieth century. It is accepted that the so-called gut-brain axis provides a two-way homeostatic communication, through immunological, hormonal and neuronal signals. A dysfunction of this axis has been associated with the pathogenesis of some diseases both within and outside the GIT, that have shown an increase in incidence over the last decades. Studies comparing germ-free animals and animals exposed to pathogenic bacterial infections, probiotics or antibiotics suggest the participation of the microbiota in this communication and a role in host defense, regulation of immunity and autoimmune disease appearance. The GIT could represent a vulnerable area through which pathogens influence all aspects of physiology and even induce CNS neuro-inflammation. All those concepts may suggest the modulation of the gut microbiota as an achievable strategy for innovative therapies in complex disorders. Moving from this background, the present review discusses the relationship between intestinal microbiota and CNS and the effects in health and disease. We particularly look at how the commensal gut microbiota influences systemic immune response in some neurological disorders, highlighting its impact on pain and cognition in multiple sclerosis, Guillain-Barrè Syndrome, neurodevelopmental and behavioral disorders and Alzheimer's disease. In this review we discuss recent studies showing that the potential microbiota-gut-brain dialogue is implicated in neurodegenerative diseases. Gaining a better understanding of the relationship between microbiota and CNS could provide an insight on the pathogenesis and therapeutic strategies of these disorders.

Delays in early neuropsychic development: Approaches to diagnosis

Directory of Open Access Journals (Sweden)

N. N. Zavadenko

2015-01-01

Full Text Available The population frequency of neuropsychic developmental delays in infants is estimated at nearly 10%; that of global intellectual disability (mental retardation is at 1-3%. Delayed development is denned as a substantial retardation as compared to the standard indicators in any of the basic spheres: motor, communicative, cognitive, adaptive-behavioral, and socioemotional ones. Global developmental delay is characterized by a significant lag in two or more spheres. The use of current diagnostic techniques, such as the Bayley or Griffiths scales, can provide an objective quantitative assessment of both an infant's overall development and indicators in individual spheres. At the preliminary examination stage, it is expedient to carry out a Denver developmental screening test that may be directly used in a doctor's consulting room. The causes of global developmental delay/intellectual disability in infants may be perinatal central nervous system (CNS lesions; brain malformations; intrauterine infections; intrauterine intoxications; early-onset psychoneurological diseases (neuroinfections, CNS injuries, epilepsies, autism spectrum disorders, etc.; congenital hypothyroidism; genetic diseases. Among all genetic causes of global developmental delay/intellectual disability, there are chromosomal anomalies (25-30%, monogenic diseases (metabolic diseases, neuroectodermal syndromes, diseases with predominant grey and white matter involvement. The diagnostic possibilities of current genetic methods are considered.

CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease?

Science.gov (United States)

Rezai-Zadeh, Kavon; Gate, David; Town, Terrence

2009-12-01

While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as "immune privilege," it is now clear that immune responses do occur in the CNS-giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue.

Differences in clinical presentation between bipolar I and II disorders in the early stages of bipolar disorder

DEFF Research Database (Denmark)

Vinberg, Maj; Mikkelsen, Rie Lambaek; Kirkegaard, Thomas

2017-01-01

Aim In a naturalistic clinical study of patients in the early stages of bipolar disorders the aim was to assess differences between patients with bipolar I (BD I) and bipolar II (BD II) disorders on clinical characteristics including affective symptoms, subjective cognitive complaints, functional...... level, the presence of comorbid personality disorders and coping strategies. Methods Diagnoses were confirmed using the Structured Clinical Interview for DSM-IV Disorders. Clinical symptoms were rated with the Young Mania Rating Scale and the Hamilton Depression Rating Scale, and functional status using...... Inventory for Stressful Situations. Results In total, 344 patients were included (BD I (n=163) and BD II (n=181). Patients with BD II presented with significantly more depressive symptoms, more cognitive complaints, lower overall functioning, and a higher prevalence of comorbid personality disorders...

The Risk of Schizophrenia and Child Psychiatric Disorders in Offspring of Mothers with Lung Cancer and Other Types of Cancer

DEFF Research Database (Denmark)

Benros, Michael Eriksen; Laursen, Thomas Munk; Dalton, Susanne Oksbjerg

2013-01-01

Maternal immune responses and brain-reactive antibodies have been proposed as possible causal mechanisms for schizophrenia and some child psychiatric disorders. According to this hypothesis maternal antibodies may cross the placenta and interact with the developing CNS of the fetus causing future...... neurodevelopmental disorders. Therefore, we investigated if children of mothers with cancer might be at higher risk of developing psychiatric disorders, with particular focus on small-cell lung cancer, which is known to induce production of antibodies binding to CNS elements....

Links between early child maltreatment, mental disorders, and cortisol secretion anomalies.

Science.gov (United States)

Bronsard, Guillaume; Auquier, Pascal; Boyer, Laurent

2016-11-01

Early child maltreatment has been widely associated with the development of mental disorders in both childhood and adulthood. However, such association cannot be systematically established, as only few factors are observed regularly, such as high prevalence of comorbidities and externalized disorders. Similarly, the association between early abuse and cortisol secretion anomalies has been well-documented. Whereas early hypercortisolism followed by hypocortisolism was often described, the results proved inconsistent and at times contradictory. The physiopathological mechanisms are quite complex and varied, including mixed neurotoxicity and stress response anomalies, linked to circadian rhythm disturbances. One of the difficulties inherent to research on this topic is to better define maltreatment in childhood. Studying children's groups at risk of maltreatment, such as children followed by juvenile justice or in child welfare systems, could be a very good tool, provided that social, judiciary, and mental health professionals are able to work together and implement common research objectives. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Community-Based Early Intervention Program for Toddlers with Autism Spectrum Disorders

Science.gov (United States)

Rollins, Pamela Rosenthal; Campbell, Michelle; Hoffman, Renee Thibodeau; Self, Kayli

2016-01-01

This study examined Pathways Early Autism Intervention, a community-based, parent-mediated, intensive behavioral and developmental intervention program for children with autism spectrum disorders that could be used as a model for state-funded early intervention programs. A single-subject, multiple-baseline, across-participants design was used.…

Early-life mental disorders and adult household income in the World Mental Health Surveys

Science.gov (United States)

Kawakami, Norito; Abdulghani, Emad Abdulrazaq; Alonso, Jordi; Bromet, Evelyn; Bruffaerts, Ronny; de Almeida, Jose Miguel Caldas; Chiu, Wai Tat; de Girolamo, Giovanni; de Graaf, Ron; Fayyad, John; Ferry, Finola; Florescu, Silvia; Gureje, Oye; Hu, Chiyi; Lakoma, Matthew D.; LeBlanc, William; Lee, Sing; Levinson, Daphna; Malhotra, Savita; Matschinger, Herbert; Medina-Mora, Maria Elena; Nakamura, Yosikazu; Browne, Mark A. Oakley; Okoliyski, Michail; Posada-Villa, Jose; Sampson, Nancy A.; Viana, Maria Carmen; Kessler, Ronald C.

2012-01-01

Background Better information on the human capital costs of early-onset mental disorders could increase sensitivity of policy-makers to the value of expanding initiatives for early detection-treatment. Data are presented on one important aspect of these costs: the associations of early-onset mental disorders with adult household income. Methods Data come from the WHO World Mental Health (WMH) Surveys in eleven high income, five upper-middle income, and six low/lower-middle income countries. Information about 15 lifetime DSM-IV mental disorders as of age of completing education, retrospectively assessed with the WHO Composite International Diagnostic Interview, was used to predict current household income among respondents ages 18-64 (n = 37,741) controlling for level of education. Gross associations were decomposed to evaluate mediating effects through major components of household income. Results Early-onset mental disorders are associated with significantly reduced household income in high and upper-middle income countries but not low/lower-middle income countries, with associations consistently stronger among women than men. Total associations are largely due to low personal earnings (increased unemployment, decreased earnings among the employed) and spouse earnings (decreased probabilities of marriage and, if married, spouse employment and low earnings of employed spouses). Individual-level effect sizes are equivalent to 16-33% of median within-country household income, while population-level effect sizes are in the range 1.0-1.4% of Gross Household Income. Conclusions Early mental disorders are associated with substantial decrements in income net of education at both individual and societal levels. Policy-makers should take these associations into consideration in making healthcare research and treatment resource allocation decisions. PMID:22521149

Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination

Directory of Open Access Journals (Sweden)

Alerie Guzman De La Fuente

2017-08-01

Full Text Available The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.

Increased Pre- and Early-Adolescent Stress in Youth with a Family History of Substance Use Disorder and Early Substance Use Initiation.

Science.gov (United States)

Charles, Nora E; Mathias, Charles W; Acheson, Ashley; Bray, Bethany C; Ryan, Stacy R; Lake, Sarah L; Liang, Yuanyuan; Dougherty, Donald M

2015-10-01

Individuals with a family history of substance use disorders (Family History Positive) are more likely to have early-onset substance use (i.e., prior to age 15), which may contribute to their higher rates of substance use disorders. One factor that may differentiate Family History Positive youth who engage in early-onset substance use from other Family History Positive youth is exposure to stressors. The aim of this study was to quantify how exposure to stressors from age 11-15 varies as a function of family history of substance use disorders and early-onset substance use. Self-reported stressors were prospectively compared in a sample of predominately (78.9%) Hispanic youth that included 68 Family History Positive youth (50% female) who initiated substance use by age 15 and demographically matched non-users with (n = 136; 52.9% female) and without (n = 75; 54.7% female) family histories of substance use disorders. Stressors were assessed at 6-month intervals for up to 4 years. Both the severity of stressors and the degree to which stressors were caused by an individual's own behavior were evaluated. All three groups differed from one another in overall exposure to stressors and rates of increase in stressors over time, with Family History Positive youth who engaged in early-onset substance use reporting the greatest exposure to stressors. Group differences were more pronounced for stressors caused by the participants' behavior. Family History Positive users had higher cumulative severity of stressors of this type, both overall and across time. These results indicate greater exposure to stressors among Family History Positive youth with early-onset substance use, and suggest that higher rates of behavior-dependent stressors may be particularly related to early-onset use.

Cerebral blood flow variations in CNS lupus

International Nuclear Information System (INIS)

Kushner, M.J.; Tobin, M.; Fazekas, F.; Chawluk, J.; Jamieson, D.; Freundlich, B.; Grenell, S.; Freemen, L.; Reivich, M.

1990-01-01

We studied the patterns of cerebral blood flow (CBF), over time, in patients with systemic lupus erythematosus and varying neurologic manifestations including headache, stroke, psychosis, and encephalopathy. For 20 paired xenon-133 CBF measurements, CBF was normal during CNS remissions, regardless of the symptoms. CBF was significantly depressed during CNS exacerbations. The magnitude of change in CBF varied with the neurologic syndrome. CBF was least affected in patients with nonspecific symptoms such as headache or malaise, whereas patients with encephalopathy or psychosis exhibited the greatest reductions in CBF. In 1 patient with affective psychosis, without clinical or CT evidence of cerebral ischemia, serial SPECT studies showed resolution of multifocal cerebral perfusion defects which paralleled clinical recovery

Effect of Early Intensive Care on Recovery from Whiplash-Associated Disorders

DEFF Research Database (Denmark)

Skillgate, Eva; Côté, Pierre; Cassidy, J. David

2016-01-01

Objective To determine whether the results from previous research suggesting that early intensive health care delays recovery from whiplash-associated disorders (WADs) were confounded by expectations of recovery and whether the association between early health care intensity and time to recovery......; 95% CI,.68-.90) had significantly slower recovery. Conclusions Our study adds to the existing evidence that early intensive care is associated with slower recovery from WAD, independent of expectation of recovery. The results have policy implications and suggest that the optimal management of WADs...

Use of early intervention for young children with autism spectrum disorder across Europe

NARCIS (Netherlands)

Salomone, E.; Beranova, S.; Bonnet-Brilhault, F.; Lauritsen, M.; Budisteanu, M.; Buitelaar, J.K.; Canal-Bedia, R.; Felhosi, G.; Fletcher-Watson, S.; Freitag, C.; Fuentes, J.; Gallagher, L.; Primo, P. Garcia; Gliga, F.; Gomot, M.; Green, J.; Heimann, M.; Jonsdottir, S.L.; Kaale, A.; Kawa, R.; Kylliainen, A.; Lemcke, S.; Markovska-Simoska, S.; Marschik, P.B.; McConachie, H.; Moilanen, I.; Muratori, F.; Narzisi, A.; Noterdaeme, M.; Oliveira, G.; Oosterling, I.; Pijl, M.; Pop-Jordanova, N.; Poustka, L.; Roeyers, H.; Roge, B.; Sinzig, J.; Vicente, A.; Warreyn, P.; Charman, T.

2016-01-01

Little is known about use of early interventions for autism spectrum disorder in Europe. Parents of children with autism spectrum disorder aged 7 years or younger (N = 1680) were recruited through parent organisations in 18 European countries and completed an online survey about the interventions

Recent Updates in the Treatment of Neurodegenerative Disorders Using Natural Compounds

Directory of Open Access Journals (Sweden)

Mahmood Rasool

2014-01-01

Full Text Available Neurodegenerative diseases are characterized by protein aggregates and inflammation as well as oxidative stress in the central nervous system (CNS. Multiple biological processes are linked to neurodegenerative diseases such as depletion or insufficient synthesis of neurotransmitters, oxidative stress, abnormal ubiquitination. Furthermore, damaging of blood brain barrier (BBB in the CNS also leads to various CNS-related diseases. Even though synthetic drugs are used for the management of Alzheimer’s disease, Parkinson’s disease, autism, and many other chronic illnesses, they are not without side effects. The attentions of researchers have been inclined towards the phytochemicals, many of which have minimal side effects. Phytochemicals are promising therapeutic agents because many phytochemicals have anti-inflammatory, antioxidative as well as anticholinesterase activities. Various drugs of either synthetic or natural origin applied in the treatment of brain disorders need to cross the BBB before they can be used. This paper covers various researches related to phytochemicals used in the management of neurodegenerative disorders.

Basic Concepts of CNS Development.

Science.gov (United States)

Nowakowski, R. S.

1987-01-01

The goals of this review are to: (1) provide a set of concepts to aid in the understanding of complex processes which occur during central nervous system (CNS) development; (2) illustrate how they contribute to our knowlege of adult brain anatomy; and (3) delineate how modifications of normal developmental processes may affect the structure and…

Early childhood adversities and risk of eating disorders in women

DEFF Research Database (Denmark)

Larsen, Janne Tidselbak; Munk-Olsen, Trine; Bulik, Cynthia M

2017-01-01

Objective: Previous studies evaluating the association between early childhood adversities and eating disorders have yielded conflicting results. The aim of this study is to examine the association between a range of adversities and risk of anorexia nervosa (AN), bulimia nervosa (BN), and eating...

Paroxetine in panic disorder: clinical management and long-term follow-up.

Science.gov (United States)

Dannon, Pinhas N; Lowengrub, Katherine; Iancu, I; Kotler, Moshe

2004-03-01

Panic disorder is one of the most common anxiety disorders and has a lifetime prevalence of 3-5%. Panic attacks can begin at any age, but commonly have their onset in early adulthood between the ages of 20 and 40 years. Naturalistic data has shown that panic disorder has a chronic and relapsing course. Panic disorder is reported to be associated with an increased risk of suicidal behavior and comorbid psychiatric diagnoses such as depression and substance abuse. Currently, recommended treatment modalities for panic disorder include the use of antidepressant pharmacotherapy and/or cognitive behavioral therapy. Paroxetine is unique among the selective serotonin reuptake inhibitors since, in addition to its effect on the CNS serotonergic neurotransmission, it also has mild noradrenergic properties demonstrated to be effective in the treatment of anxiety disorders and depression. Paroxetine treatment has the potential to cause weight gain and sexual dysfunction, primarily anorgasmia and ejaculatory dysfunction for the long term. In the short-term, treatment causes nausea, gastrointestinal disturbances, irritability, headaches and eating and sleeping difficulties. Paroxetine is an example of an selective serotonin reuptake inhibitor agent, which has been well studied in the treatment of panic disorder and is efficacious and well-tolerated. Paroxetine pharmacotherapy has been recommended to be continued for 1 year as specified in the treatment guidelines set by the American Psychiatric Association in the treatment of panic disorder.

DEFINING RELATIONAL PATHOLOGY IN EARLY CHILDHOOD: THE DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD DC:0-5 APPROACH.

Science.gov (United States)

Zeanah, Charles H; Lieberman, Alicia

2016-09-01

Infant mental health is explicitly relational in its focus, and therefore a diagnostic classification system for early childhood disorders should include attention not only to within-the-child psychopathology but also between child and caregiver psychopathology. In this article, we begin by providing a review of previous efforts to introduce this approach that date back more than 30 years. Next, we introduce changes proposed in the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood DC:0-5 (ZERO TO THREE, in press). In a major change from previous attempts, the DC:0-5 includes an Axis I "Relationship Specific Disorder of Early Childhood." This disorder intends to capture disordered behavior that is limited to one caregiver relationship rather than cross contextually. An axial characterization is continued from the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood DC:0-3R (ZERO TO THREE, 2005), but two major changes are introduced. First, the DC:0-5 proposes to simplify ratings of relationship adaptation/maladaptation, and to expand what is rated so that in addition to characterizing the child's relationship with his or her primary caregiver, there also is a characterization of the network of family relationships in which the child develops. This includes coparenting relationships and the entire network of close relationships that impinge on the young child's development and adaptation. © 2016 Michigan Association for Infant Mental Health.

Impact of early adolescent anxiety disorders on self-esteem development from adolescence to young adulthood

Science.gov (United States)

Maldonado, Lizmarie; Huang, Yangxin; Chen, Ren; Kasen, Stephanie; Cohen, Patricia; Chen, Henian

2013-01-01

Purpose To examine the association between early adolescent anxiety disorders and self-esteem development from early adolescence to young adulthood. Methods Self-esteem was measured at mean ages 13, 16 and 22 for 821 participants from the Children in the Community Study, a population-based longitudinal cohort. Anxiety disorders were measured at mean age 13 years. Multilevel growth models were employed to analyze the change in self-esteem from early adolescence to young adulthood and to evaluate whether adolescent anxiety disorders predict both average and slope of self-esteem development. Results Self-esteem increased during adolescence and continued to increase in young adulthood. Girls had lower average self-esteem than boys, but this difference disappeared when examining the effect of anxiety. Adolescents with anxiety disorder had lower self-esteem, on average, compared with healthy adolescents (effect size (ES) =−0.35, pself-esteem (ES=−0.30, pself-esteem from adolescence to young-adulthood ( =−0.1, pself-esteem development. Conclusions All but one of the assessed adolescent anxiety disorders were related to lower self-esteem, with social phobia having the greatest impact. OCD predicted a decline in self-esteem trajectory with age. The importance of raising self-esteem in adolescents with anxiety and other mental disorders is discussed. PMID:23648133

HB-GAM (pleiotrophin) reverses inhibition of neural regeneration by the CNS extracellular matrix

Science.gov (United States)

Paveliev, Mikhail; Fenrich, Keith K.; Kislin, Mikhail; Kuja-Panula, Juha; Kulesskiy, Evgeny; Varjosalo, Markku; Kajander, Tommi; Mugantseva, Ekaterina; Ahonen-Bishopp, Anni; Khiroug, Leonard; Kulesskaya, Natalia; Rougon, Geneviève; Rauvala, Heikki

2016-01-01

Chondroitin sulfate (CS) glycosaminoglycans inhibit regeneration in the adult central nervous system (CNS). We report here that HB-GAM (heparin-binding growth-associated molecule; also known as pleiotrophin), a CS-binding protein expressed at high levels in the developing CNS, reverses the role of the CS chains in neurite growth of CNS neurons in vitro from inhibition to activation. The CS-bound HB-GAM promotes neurite growth through binding to the cell surface proteoglycan glypican-2; furthermore, HB-GAM abrogates the CS ligand binding to the inhibitory receptor PTPσ (protein tyrosine phosphatase sigma). Our in vivo studies using two-photon imaging of CNS injuries support the in vitro studies and show that HB-GAM increases dendrite regeneration in the adult cerebral cortex and axonal regeneration in the adult spinal cord. Our findings may enable the development of novel therapies for CNS injuries. PMID:27671118

Early Intervention Outcomes for Toddlers with Autism Spectrum Disorder and Their Families

Science.gov (United States)

Noyes-Grosser, Donna M.; Elbaum, Batya; Wu, Yan; Siegenthaler, Kirsten M.; Cavalari, Rachel S.; Gillis, Jennifer M.; Romanczyk, Raymond G.

2018-01-01

Autism spectrum disorder (ASD) can be diagnosed as early as 18 months of age. State Early Intervention (EI) programs under Part C of the Individuals with Disabilities Education Act (IDEA) are serving increasing numbers of children with ASD; however, little is known about outcomes of these services. This study evaluated the impact of EI for…

Early improvement in eating attitudes during cognitive behavioural therapy for eating disorders: the impact of personality disorder cognitions.

Science.gov (United States)

Park, Emma C; Waller, Glenn; Gannon, Kenneth

2014-03-01

The personality disorders are commonly comorbid with the eating disorders. Personality disorder pathology is often suggested to impair the treatment of axis 1 disorders, including the eating disorders. This study examined whether personality disorder cognitions reduce the impact of cognitive behavioural therapy (CBT) for eating disorders, in terms of treatment dropout and change in eating disorder attitudes in the early stages of treatment. Participants were individuals with a diagnosed eating disorder, presenting for individual outpatient CBT. They completed measures of personality disorder cognitions and eating disorder attitudes at sessions one and six of CBT. Drop-out rates prior to session six were recorded. CBT had a relatively rapid onset of action, with a significant reduction in eating disorder attitudes over the first six sessions. Eating disorder attitudes were most strongly associated with cognitions related to anxiety-based personality disorders (avoidant, obsessive-compulsive and dependent). Individuals who dropped out of treatment prematurely had significantly higher levels of dependent personality disorder cognitions than those who remained in treatment. For those who remained in treatment, higher levels of avoidant, histrionic and borderline personality disorder cognitions were associated with a greater change in global eating disorder attitudes. CBT's action and retention of patients might be improved by consideration of such personality disorder cognitions when formulating and treating the eating disorders.

Early Life Stress Effects on Glucocorticoid—BDNF Interplay in the Hippocampus

Science.gov (United States)

Daskalakis, Nikolaos P.; De Kloet, Edo Ronald; Yehuda, Rachel; Malaspina, Dolores; Kranz, Thorsten M.

2015-01-01

Early life stress (ELS) is implicated in the etiology of multiple psychiatric disorders. Important biological effects of ELS are manifested in stress-susceptible regions of the hippocampus and are partially mediated by long-term effects on glucocorticoid (GC) and/or neurotrophin signaling pathways. GC-signaling mediates the regulation of stress response to maintain homeostasis, while neurotrophin signaling plays a key role in neuronal outgrowth and is crucial for axonal guidance and synaptic integrity. The neurotrophin and GC-signaling pathways co-exist throughout the central nervous system (CNS), particularly in the hippocampus, which has high expression levels of glucocorticoid-receptors (GR) and mineralocorticoid-receptors (MR) as well as brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB). This review addresses the effects of ELS paradigms on GC- and BDNF-dependent mechanisms and their crosstalk in the hippocampus, including potential implications for the pathogenesis of common stress-related disorders. PMID:26635521

Association between infection early in life and mental disorders among youth in the community: a cross-sectional study

Directory of Open Access Journals (Sweden)

Goodwin Renee D

2011-11-01

Full Text Available Abstract Background The objective of this study was to examine the association between infection early in life and mental disorders among youth in the community. Methods Data were drawn from the MECA (Methods in Epidemiology of Child and Adolescent psychopathology, a community-based study of 1,285 youth in the United States conducted in 1992. Multiple logistic regression analyses were used to investigate the association between parent/caregiver-reported infection early in life and DSM/DISC diagnoses of mental disorders at ages 9-17. Results Infection early in life was associated with a significantly increased odds of major depression (OR = 3.9, social phobia (OR = 5.8, overanxious disorder (OR = 6.1, panic disorder (OR = 12.1, and oppositional defiant disorder (OR = 3.7. Conclusions These findings are consistent with and extend previous results by providing new evidence suggesting a link between infection early in life and increased risk of depression and anxiety disorders among youth. These results should be considered preliminary. Replication of these findings with longitudinal epidemiologic data is needed. Possible mechanisms are discussed.

Problems of prophylactic CNS radiotherapy in acute children's leukemia

International Nuclear Information System (INIS)

Bek, V.; Pribylova, O.; Abrahamova, J.; Hynieova, H.; Hrodek, O.

1980-01-01

The prophylactic treatment of the CNS was conducted by cobalt teletherapy of the cranium and by intrathecal application of MTX after the induction of primary remission in 70 children with acute leukemia throughout 5 years up to the end of 1978. The method of the combined radio- and chemoprophylaxis of the CNS was being changed during the years, especially as far as the radiation dose for the cranium was concerned. A detailed analysis made in a group of 59 children with the minimum interval of 18 months from the beginning of the treatment showed the best results after the application of a dose of 24 Gy/3 weeks. Following this procedure the relapse of leukemia in the CNS occurred in 9% only, whereas on the application of doses of 20 Gy and lower it occurred in 35 to 40%. On the whole 24 out of 59 children, i.e. 41%, are surviving, 35 children, i.e. 59%, died. Mostly complete, but only temporary, epilation was an invariable consequence of the irradiation of the cranium. The somnolence syndrome was only sporadically observed. It cannot be excluded, however, that some of its forms in patients discharged from hospital escaped attention. No case was recorded of serious impairment of the CNS of the leukoencephalopathic type. Up to now the psychomotor, intellectual and emotional development of the surviving children has been normal. (author)

VIIP: Central Nervous System (CNS) Modeling

Science.gov (United States)

Vera, Jerry; Mulugeta, Lealem; Nelson, Emily; Raykin, Julia; Feola, Andrew; Gleason, Rudy; Samuels, Brian; Ethier, C. Ross; Myers, Jerry

2015-01-01

Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome. It has been hypothesized that the headward shift of cerebrospinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn may then induce VIIP syndrome through interaction with various biomechanical pathways. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the related IWS works submitted by Nelson et al., Feola et al. and Ethier et al.

CNS metastasis from malignant uveal melanoma: a clinical and histopathological characterisation

DEFF Research Database (Denmark)

Holfort, S K; Lindegaard, J; Isager, P

2008-01-01

was observed in two cases (14%). The amount of tumour infiltrating lymphocytes was pronounced in three cases (23%). CONCLUSION: The proportion of uveal melanoma patients having CNS metastasis was 0.7%. Eleven patients had multiple organ metastases, and the average time from the initial CNS symptoms to death...

DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD DC:0-5: SELECTIVE REVIEWS FROM A NEW NOSOLOGY FOR EARLY CHILDHOOD PSYCHOPATHOLOGY.

Science.gov (United States)

Zeanah, Charles H; Carter, Alice S; Cohen, Julie; Egger, Helen; Gleason, Mary Margaret; Keren, Miri; Lieberman, Alicia; Mulrooney, Kathleen; Oser, Cindy

2016-09-01

The Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-5; ZERO TO THREE) is scheduled to be published in 2016. The articles in this section are selective reviews that have been undertaken as part of the process of refining and updating the nosology. They provide the rationales for new disorders, for disorders that had not been included previously in the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-3R; ZERO TO THREE, 2005), and for changes in how certain types of disorders are conceptualized. © 2016 Michigan Association for Infant Mental Health.

Interneuron progenitor transplantation to treat CNS dysfunction

Directory of Open Access Journals (Sweden)

Muhammad O Chohan

2016-08-01

Full Text Available Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field.

Altered energy production, lowered antioxidant potential, and inflammatory processes mediate CNS damage associated with abuse of the psychostimulants MDMA and methamphetamine

Science.gov (United States)

Downey, Luke A.; Loftis, Jennifer M.

2014-01-01

Central nervous system (CNS) damage associated with psychostimulant dependence may be an ongoing, degenerative process with adverse effects on neuropsychiatric function. However, the molecular mechanisms regarding how altered energy regulation affects immune response in the context of substance use disorders are not fully understood. This review summarizes the current evidence regarding the effects of psychostimulant [particularly 3,4-methylenedioxy-N-methylamphetamine (MDMA) and methamphetamine] exposure on brain energy regulation, immune response, and neuropsychiatric function. Importantly, the neuropsychiatric impairments (e.g., cognitive deficits, depression, and anxiety) that persist following abstinence are associated with poorer treatment outcomes – increased relapse rates, lower treatment retention rates, and reduced daily functioning. Qualifying the molecular changes within the CNS according to the exposure and use patterns of specifically abused substances should inform the development of new therapeutic approaches for addiction treatment. PMID:24485894

Toward early markers for Autism Spectrum Disorder using eye tracking

NARCIS (Netherlands)

Hessels, R.S.|info:eu-repo/dai/nl/374642001

2017-01-01

The goal of this dissertation was to explore two possible early markers of Autism Spectrum Disorder (ASD): visual search superiority, and gaze behavior during face perception. These possible markers were explored as they pertain to both the social deficits in ASD (gaze during face perception) and

Neuroprotective effects of estrogen in CNS injuries: insights from animal models

Directory of Open Access Journals (Sweden)

Raghava N

2017-07-01

Full Text Available Narayan Raghava,1 Bhaskar C Das,2 Swapan K Ray1 1Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA; 2Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA Abstract: Among the estrogens that are biosynthesized in the human body, 17β-estradiol (estradiol or E2 is the most common and the best estrogen for neuroprotection in animal models of the central nervous system (CNS injuries such as spinal cord injury (SCI, traumatic brain injury (TBI, and ischemic brain injury (IBI. These CNS injuries are not only serious health problems, but also enormous economic burden on the patients, their families, and the society at large. Studies from animal models of these CNS injuries provide insights into the multiple neuroprotective mechanisms of E2 and also suggest the possibility of translating the therapeutic efficacy of E2 in the treatment SCI, TBI, and IBI in humans in the near future. The pathophysiology of these injuries includes loss of motor function in the limbs, arms and their extremities, cognitive deficit, and many other serious consequences including life-threatening paralysis, infection, and even death. The potential application of E2 therapy to treat the CNS injuries may become a trend as the results are showing significant therapeutic benefits of E2 for neuroprotection when administered into the animal models of SCI, TBI, and IBI. This article describes the plausible mechanisms how E2 works with or without the involvement of estrogen receptors and provides an overview of the known neuroprotective effects of E2 in these three CNS injuries in different animal models. Because activation of estrogen receptors has profound implications in maintaining and also affecting normal physiology, there are notable impediments in translating E2 therapy to the clinics for neuroprotection in CNS injuries in humans. While E2 may not yet be the sole molecule for

Use of Early Intervention for Young Children with Autism Spectrum Disorder across Europe

Science.gov (United States)

Salomone, Erica; Beranová, Štepánka; Bonnet-Brilhault, Frédérique; Briciet Lauritsen, Marlene; Budisteanu, Magdalena; Buitelaar, Jan; Canal-Bedia, Ricardo; Felhosi, Gabriella; Fletcher-Watson, Sue; Freitag, Christine; Fuentes, Joaquin; Gallagher, Louise; Garcia Primo, Patricia; Gliga, Fotinica; Gomot, Marie; Green, Jonathan; Heimann, Mikael; Jónsdóttir, Sigridur Loa; Kaale, Anett; Kawa, Rafal; Kylliainen, Anneli; Lemcke, Sanne; Markovska-Simoska, Silvana; Marschik, Peter B; McConachie, Helen; Moilanen, Irma; Muratori, Filippo; Narzisi, Antonio; Noterdaeme, Michele; Oliveira, Guiomar; Oosterling, Iris; Pijl, Mirjam; Pop-Jordanova, Nada; Poustka, Luise; Roeyers, Herbert; Rogé, Bernadette; Sinzig, Judith; Vicente, Astrid; Warreyn, Petra; Charman, Tony

2016-01-01

Little is known about use of early interventions for autism spectrum disorder in Europe. Parents of children with autism spectrum disorder aged 7?years or younger (N?=?1680) were recruited through parent organisations in 18 European countries and completed an online survey about the interventions their child received. There was considerable…

Early Intervening for Students with Speech Sound Disorders: Lessons from a School District

Science.gov (United States)

Mire, Stephen P.; Montgomery, Judy K.

2009-01-01

The concept of early intervening services was introduced into public school systems with the implementation of the Individuals With Disabilities Education Improvement Act (IDEA) of 2004. This article describes a program developed for students with speech sound disorders that incorporated concepts of early intervening services, response to…

Foxp3+ regulatory T cells control persistence of viral CNS infection.

Directory of Open Access Journals (Sweden)

Dajana Reuter

Full Text Available We earlier established a model of a persistent viral CNS infection using two week old immunologically normal (genetically unmodified mice and recombinant measles virus (MV. Using this model infection we investigated the role of regulatory T cells (Tregs as regulators of the immune response in the brain, and assessed whether the persistent CNS infection can be modulated by manipulation of Tregs in the periphery. CD4(+ CD25(+ Foxp3(+ Tregs were expanded or depleted during the persistent phase of the CNS infection, and the consequences for the virus-specific immune response and the extent of persistent infection were analyzed. Virus-specific CD8(+ T cells predominantly recognising the H-2D(b-presented viral hemagglutinin epitope MV-H(22-30 (RIVINREHL were quantified in the brain by pentamer staining. Expansion of Tregs after intraperitoneal (i.p. application of the superagonistic anti-CD28 antibody D665 inducing transient immunosuppression caused increased virus replication and spread in the CNS. In contrast, depletion of Tregs using diphtheria toxin (DT in DEREG (depletion of regulatory T cells-mice induced an increase of virus-specific CD8(+ effector T cells in the brain and caused a reduction of the persistent infection. These data indicate that manipulation of Tregs in the periphery can be utilized to regulate virus persistence in the CNS.

Management of CNS tumors

International Nuclear Information System (INIS)

Griem, M.L.

1987-01-01

The treatment of tumors of the CNS has undergone a number of changes based on the impact of CT. The use of intraoperative US for the establishment of tumor location and tumor histology is demonstrated. MR imaging also is beginning to make an impact on the diagnosis and treatment of tumors of the CNS. Examples of MR images are shown. The authors then discuss the important aspects of tumor histology as it affects management and newer concepts in surgery, radiation, and chemotherapy on tumor treatment. The role of intraoperative placement of radioactive sources, the utilization of heavy particle radiation therapy, and the potential role of other experimental radiation therapy techniques are discussed. The role of hyperfractionated radiation and of neutrons and x-ray in a mixed-beam treatment are discussed in perspective with standard radiation therapy. Current chemotherapy techniques, including intraarterial chemotherapy, are discussed. The complications of radiation therapy alone and in combination with chemotherapy in the management of primary brain tumors, brain metastases, and leukemia are reviewed. A summary of the current management of pituitary tumors, including secreting pituitary adenomas and chromophobe adenomas, are discussed. The treatment with heavy particle radiation, transsphenoidal microsurgical removal, and combined radiotherapeutic and surgical management are considered. Tumor metastasis management of lesions of the brain and spinal cord are considered

Early Onset Bipolar Spectrum Disorder: Psychopharmacological, Psychological, and Educational Management

Science.gov (United States)

McIntosh, David E.; Trotter, Jeffrey S.

2006-01-01

Although published research continues to advocate medication as the first line of treatment for early onset bipolar spectrum disorder (EOBSD; N. Lofthouse & M.A. Fristad, 2004), preliminary research demonstrating the utility of cognitive, cognitive-behavioral, and psychoeducational therapies is promising. It appears as if future treatment of EOBSD…

Novel agents in CNS myeloma treatment.

Science.gov (United States)

Gozzetti, Alessandro; Cerase, Alfonso

2014-01-01

Central nervous system localization of multiple myeloma (CNS-MM) accounts for about 1% of all MM.Treatment is still unsatisfactory. Many treatments have been described in the literature: chemotherapy (CHT), intrathecal therapy (IT), and radiotherapy (RT), with survivals reported between one month and six months. Recent drugs such as the immunomodulatory drugs (IMiDs) and proteasome inhibitors (bortezomib) have changed the treatment of patients with MM, both younger and older, with a significant improvement in response and survival. The activity of new drugs in CNSMM has been reported but is still not well known. Bortezomib does not cross the blood brain barrier (BBB), and IMID’s seem to have only a minimal crossover. The role of novel agents in CNS MM management will be discussed as well as the potential role of other new immunomodulatory drugs (pomalidomide) and proteasome inhibitors that seem to cross the BBB and hold promise into the treatment of this rare and still incurable localization of the disease.

Stable Early Maternal Report of Behavioral Inhibition Predicts Lifetime Social Anxiety Disorder in Adolescence

Science.gov (United States)

Chronis-Tuscano, Andrea; Degnan, Kathryn Amey; Pine, Daniel S.; Perez-Edgar, Koraly; Henderson, Heather A.; Diaz, Yamalis; Raggi, Veronica L.; Fox, Nathan A.

2009-01-01

The odds of a lifetime diagnosis of social anxiety disorder increased by 3.79 times for children who had a stable report of behavioral inhibition from their mothers. This finding has important implications for the early identification and prevention of social anxiety disorder.

Impact of early adolescent anxiety disorders on self-esteem development from adolescence to young adulthood.

Science.gov (United States)

Maldonado, Lizmarie; Huang, Yangxin; Chen, Ren; Kasen, Stephanie; Cohen, Patricia; Chen, Henian

2013-08-01

To examine the association between early adolescent anxiety disorders and self-esteem development from early adolescence through young adulthood. Self-esteem was measured at mean ages 13, 16, and 22 for 821 participants from the Children in the Community Study, a population-based longitudinal cohort. Anxiety disorders were measured at mean age 13 years. Multilevel growth models were employed to analyze the change in self-esteem from early adolescence to young adulthood and to evaluate whether adolescent anxiety disorders predict both average and slope of self-esteem development. Self-esteem increased during adolescence and continued to increase in young adulthood. Girls had lower average self-esteem than boys, but this difference disappeared when examining the effect of anxiety. Adolescents with anxiety disorder had lower self-esteem, on average, compared with healthy adolescents (effect size [ES] = -.35, p self-esteem (ES = -.30, p self-esteem from adolescence to young adulthood (β = -.1, p self-esteem development. All but one of the assessed adolescent anxiety disorders were related to lower self-esteem, with social phobia having the greatest impact. OCD predicted a decline in self-esteem trajectory with age. The importance of raising self-esteem in adolescents with anxiety and other mental disorders is discussed. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Informing early intervention: preschool predictors of anxiety disorders in middle childhood.

Directory of Open Access Journals (Sweden)

Jennifer L Hudson

Full Text Available BACKGROUND: To inform early intervention practice, the present research examines how child anxiety, behavioural inhibition, maternal overinvolvement, maternal negativity, mother-child attachment and maternal anxiety, as assessed at age four, predict anxiety at age nine. METHOD: 202 children (102 behaviourally inhibited and 100 behaviourally uninhibited aged 3-4 years were initially recruited and the predictors outlined above were assessed. Diagnostic assessments, using the Anxiety Disorders Interview Schedule, were then conducted five years later. RESULTS: Behavioural inhibition, maternal anxiety, and maternal overinvolvement were significant predictors of clinical anxiety, even after controlling for baseline anxiety (p.1. CONCLUSIONS: Preschool children who show anxiety, are inhibited, have overinvolved mothers and mothers with anxiety disorders are at increased risk for anxiety in middle childhood. These factors can be used to identify suitable participants for early intervention and can be targeted within intervention programs.

Early Life Stress Effects on the Glucocorticoid - BDNF interplay in the Hippocampus

Directory of Open Access Journals (Sweden)

Nikolaos P Daskalakis

2015-11-01

Full Text Available Early life stress (ELS is implicated in the etiology of multiple psychiatric disorders. Important biological effects of ELS are manifested in stress-susceptible regions of the hippocampus and are partially mediated by long-term effects on glucocorticoid and/or neurotrophin signaling pathways. Glucocorticoid (GC signaling mediates the regulation of the stress response to maintain homeostasis, while neurotrophin signaling plays a key role in neuronal outgrowth and is crucial for axonal guidance and synaptic integrity. The neurotrophin and glucocorticoid signaling pathways co-exist throughout the central nervous system (CNS, particularly in the hippocampus, which has high expression of glucocorticoid and mineralocorticoid receptors (GR and MR as well as brain-derived neurotrophic factor (BDNF and its receptor, tropomyosin-related kinase receptor B (TrkB. This review addresses the effects of ELS paradigms on GC- and BDNF- dependent mechanisms and their crosstalk in the hippocampus, including potential implications for the pathogenesis of common stress-related disorders.

Early brain enlargement and elevated extra-axial fluid in infants who develop autism spectrum disorder.

Science.gov (United States)

Shen, Mark D; Nordahl, Christine W; Young, Gregory S; Wootton-Gorges, Sandra L; Lee, Aaron; Liston, Sarah E; Harrington, Kayla R; Ozonoff, Sally; Amaral, David G

2013-09-01

Prospective studies of infants at risk for autism spectrum disorder have provided important clues about the early behavioural symptoms of autism spectrum disorder. Diagnosis of autism spectrum disorder, however, is not currently made until at least 18 months of age. There is substantially less research on potential brain-based differences in the period between 6 and 12 months of age. Our objective in the current study was to use magnetic resonance imaging to identify any consistently observable brain anomalies in 6-9 month old infants who would later develop autism spectrum disorder. We conducted a prospective infant sibling study with longitudinal magnetic resonance imaging scans at three time points (6-9, 12-15, and 18-24 months of age), in conjunction with intensive behavioural assessments. Fifty-five infants (33 'high-risk' infants having an older sibling with autism spectrum disorder and 22 'low-risk' infants having no relatives with autism spectrum disorder) were imaged at 6-9 months; 43 of these (27 high-risk and 16 low-risk) were imaged at 12-15 months; and 42 (26 high-risk and 16 low-risk) were imaged again at 18-24 months. Infants were classified as meeting criteria for autism spectrum disorder, other developmental delays, or typical development at 24 months or later (mean age at outcome: 32.5 months). Compared with the other two groups, infants who developed autism spectrum disorder (n = 10) had significantly greater extra-axial fluid at 6-9 months, which persisted and remained elevated at 12-15 and 18-24 months. Extra-axial fluid is characterized by excessive cerebrospinal fluid in the subarachnoid space, particularly over the frontal lobes. The amount of extra-axial fluid detected as early as 6 months was predictive of more severe autism spectrum disorder symptoms at the time of outcome. Infants who developed autism spectrum disorder also had significantly larger total cerebral volumes at both 12-15 and 18-24 months of age. This is the first magnetic

The impact of early symptom change and therapeutic alliance on treatment outcome in cognitive-behavioural therapy for eating disorders.

Science.gov (United States)

Turner, Hannah; Bryant-Waugh, Rachel; Marshall, Emily

2015-10-01

The present study explored the impact of early symptom change (cognitive and behavioural) and the early therapeutic alliance on treatment outcome in cognitive-behavioural therapy (CBT) for the eating disorders. Participants were 94 adults with diagnosed eating disorders who completed a course of CBT in an out-patient community eating disorders service in the UK. Patients completed a measure of eating disorder psychopathology at the start of treatment, following the 6th session and at the end of treatment. They also completed a measure of therapeutic alliance following the 6th session. Greater early reduction in dietary restraint and eating concerns, and smaller levels of change in shape concern, significantly predicted later reduction in global eating pathology. The early therapeutic alliance was strong across the three domains of tasks, goals and bond. Early symptom reduction was a stronger predictor of later reduction in eating pathology than early therapeutic alliance. The early therapeutic alliance did not mediate the relationship between early symptom reduction and later reduction in global eating pathology. Instead, greater early symptom reduction predicted a strong early therapeutic alliance. Early clinical change was the strongest predictor of treatment outcome and this also facilitated the development of a strong early alliance. Clinicians should be encouraged to deliver all aspects of evidence-based CBT, including behavioural change. The findings suggest that this will have a positive impact on both the early therapeutic alliance and later change in eating pathology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Injuries in Children with Autism Spectrum Disorder: Study to Explore Early Development (SEED)

Science.gov (United States)

DiGuiseppi, Carolyn; Levy, Susan E.; Sabourin, Katherine R.; Soke, Gnakub N.; Rosenberg, Steven; Lee, Li-Ching; Moody, Eric; Schieve, Laura A.

2018-01-01

This study examined caregiver-reported medically-attended injuries among 30-68 month old children with autism spectrum disorder (ASD) compared to general population (POP) and non-ASD developmental disorders (DD) controls in the Study to Explore Early Development. Injuries were common in ASD cases (32.3%) as well as POP (30.2%) and DD (27.8%)…

Scoping the evidence for EarlyBird and EarlyBird Plus, two United Kingdom-developed parent education training programmes for autism spectrum disorder.

Science.gov (United States)

Dawson-Squibb, John-Joe; Davids, Eugene Lee; de Vries, Petrus J

2018-03-01

EarlyBird and EarlyBird Plus are parent education and training programmes designed by the UK National Autistic Society in 1997 and 2003, having been delivered to more than 27,000 families in 14 countries. These group-based programmes aim to (1) support parents immediately after diagnosis of autism spectrum disorder, (2) empower parents, encouraging a positive perception of their child's autism spectrum disorder and (3) help parents establish good practice. In the absence of any previous comprehensive review, we performed a scoping review of all peer-reviewed publications on EarlyBird/EarlyBird Plus. A search was conducted between February and June 2016 using EbscoHost, Sabinet, SAGE Journals, Directory of Open Access Journals, BioMed Central, Scopus, ScienceDirect and grey literature. Two reviewers independently screened titles and abstracts for inclusion. In total, 18 articles were identified: 16 from the United Kingdom and 2 from New Zealand. We reviewed the context, study populations, design, outcome measures, whether focus was on parental perception, parental change or child changes and programme feasibility. Strong parental support for the acceptability but lower level evidence of efficacy of EarlyBird/EarlyBird Plus was found. Future research should consider randomised controlled trials. There is no research on EarlyBird/EarlyBird Plus in low-resource settings; therefore, we recommend broader feasibility evaluation of EarlyBird/EarlyBird Plus including accessibility, cultural appropriateness and scalability.

Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas

2014-01-01

BACKGROUND: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. PROCEDURE: To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744...... leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CONCLUSION: CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia....

Is ADHD an early stage in the development of borderline personality disorder?

Science.gov (United States)

Storebø, Ole Jakob; Simonsen, Erik

2014-07-01

Several studies report associations between adults with borderline personality disorder (BPD) and a history of attention-deficit hyperactivity (ADHD) symptoms in childhood. To explore the association between BPD and a history of ADHD in childhood. A comprehensive search of EMBASE, PsychInfo and Medline and hand-searching yielded 238 "hits". Fifteen articles were found to have sufficient quality and relevance to be included in the final review. The data were considered in six possible explanatory psychopathological models of the association between ADHD and BPD. Most of the 15 articles showed a statistical association between ADHD and BPD. The data, most strongly provided a basis for the hypotheses that ADHD is either an early developmental stage of BPD, or that the two disorders share an environmental and genetic aetiology. Furthermore, one of the disorders seems to give a synergic effect, reinforce the other or complicate the disorders. In one prospective study, the risk factor for children with ADHD to develop BPD was as high as odds ratio 13.16. No studies have looked at treatment of ADHD as a mediator of the risk for BPD. Many studies pointed at shared aetiology or the risk for development of one disorder, when the other disorder is present. The data do not evaluate how treatment factors or other factors mediate the risk or how overlap of diagnostic criteria adds to the statistical association. More research is much needed, in particular studies looking at early intervention and which treatment of ADHD that might prevent later development of BPD.

Ethnopharmacological survey of plant species used in folk medicine against central nervous system disorders in Togo.

Science.gov (United States)

Kantati, Yendube T; Kodjo, K Magloire; Dogbeavou, Koffi S; Vaudry, David; Leprince, Jérôme; Gbeassor, Messanvi

2016-04-02

Neurological diseases are rising all around the world. In a developing country such as Togo, although plant-based medicines are the only means, still very little is known regarding the nature and efficiency of medicinal plants used by indigenous people to manage central nervous system (CNS) disorders. This study, an ethnobotanical survey, aimed to report plant species used in traditional medicine (TM) for the management of various CNS disorders in Togo. 52 traditional actors (TA) including 33 traditional healers (TH) and 19 medicinal plant sellers (MPS) were interviewed, using a questionnaire mentioning informants' general data and uses of medicinal plants. The present study reports 44 medicinal plant species distributed into 26 families, mentioning scientific and common local names, plant organs used, preparation method, root of administration and putative applications. It appears that there is a real knowledge on medicinal plants used for traditional treatment of CNS disorders in Togo and that the local flora abounds of potentially neuroactive plants which could be useful for the discovery of antipsychotic or neuroprotective molecules. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Electrophysiological CNS-processes related to associative learning in humans.

Science.gov (United States)

Christoffersen, Gert R J; Schachtman, Todd R

2016-01-01

The neurophysiology of human associative memory has been studied with electroencephalographic techniques since the 1930s. This research has revealed that different types of electrophysiological processes in the human brain can be modified by conditioning: sensory evoked potentials, sensory induced gamma-band activity, periods of frequency-specific waves (alpha and beta waves, the sensorimotor rhythm and the mu-rhythm) and slow cortical potentials. Conditioning of these processes has been studied in experiments that either use operant conditioning or repeated contingent pairings of conditioned and unconditioned stimuli (classical conditioning). In operant conditioning, the appearance of a specific brain process is paired with an external stimulus (neurofeedback) and the feedback enables subjects to obtain varying degrees of control of the CNS-process. Such acquired self-regulation of brain activity has found practical uses for instance in the amelioration of epileptic seizures, Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). It has also provided communicative means of assistance for tetraplegic patients through the use of brain computer interfaces. Both extra and intracortically recorded signals have been coupled with contingent external feedback. It is the aim for this review to summarize essential results on all types of electromagnetic brain processes that have been modified by classical or operant conditioning. The results are organized according to type of conditioned EEG-process, type of conditioning, and sensory modalities of the conditioning stimuli. Copyright © 2015 Elsevier B.V. All rights reserved.

Early life programming as a target for prevention of child and adolescent mental disorders

OpenAIRE

Lewis, Andrew James; Galbally, Megan; Gannon, Tara; Symeonides, Christos

2014-01-01

This paper concerns future policy development and programs of research for the prevention of mental disorders based on research emerging from fetal and early life programming. The current review offers an overview of findings on pregnancy exposures such as maternal mental health, lifestyle factors, and potential teratogenic and neurotoxic exposures on child outcomes. Outcomes of interest are common child and adolescent mental disorders including hyperactive, behavioral and emotional disorders...

CNS effects following the treatment of malignancy

International Nuclear Information System (INIS)

Rane, N.; Quaghebeur, G.

2012-01-01

Corporeal and central nervous system (CNS) axis chemotherapy and radiotherapy have long been used for the effective treatment and prophylaxis of CNS, body malignancies, and leukaemias. However, they are not without their problems. Following the proliferation of magnetic resonance neuroimaging in recent years it has become clear that the spectrum of toxicity that these therapies produce ranges from subclinical white matter changes to overt brain necrosis. The effects are both direct and indirect and via different pathological mechanisms. Chronic and progressive changes can be detected many years after the initial intervention. In addition to leucoencephalopathic changes, grey matter changes are now well described. Changes may be difficult to distinguish from tumour recurrence, though may be reversible and remediable, and are thus very important to differentiate. In this review toxic effects are classified and their imaging appearances discussed, with reference to specific syndromes.

Mechanisms of CNS invasion and damage by parasites.

Science.gov (United States)

Kristensson, Krister; Masocha, Willias; Bentivoglio, Marina

2013-01-01

Invasion of the central nervous system (CNS) is a most devastating complication of a parasitic infection. Several physical and immunological barriers provide obstacles to such an invasion. In this broad overview focus is given to the physical barriers to neuroinvasion of parasites provided at the portal of entry of the parasites, i.e., the skin and epithelial cells of the gastrointestinal tract, and between the blood and the brain parenchyma, i.e., the blood-brain barrier (BBB). A description is given on how human pathogenic parasites can reach the CNS via the bloodstream either as free-living or extracellular parasites, by embolization of eggs, or within red or white blood cells when adapted to intracellular life. Molecular mechanisms are discussed by which parasites can interact with or pass across the BBB. The possible targeting of the circumventricular organs by parasites, as well as the parasites' direct entry to the brain from the nasal cavity through the olfactory nerve pathway, is also highlighted. Finally, examples are given which illustrate different mechanisms by which parasites can cause dysfunction or damage in the CNS related to toxic effects of parasite-derived molecules or to immune responses to the infection. Copyright © 2013 Elsevier B.V. All rights reserved.

Brain Age in Early Stages of Bipolar Disorders or Schizophrenia.

Science.gov (United States)

Hajek, Tomas; Franke, Katja; Kolenic, Marian; Capkova, Jana; Matejka, Martin; Propper, Lukas; Uher, Rudolf; Stopkova, Pavla; Novak, Tomas; Paus, Tomas; Kopecek, Miloslav; Spaniel, Filip; Alda, Martin

2017-12-20

The greater presence of neurodevelopmental antecedants may differentiate schizophrenia from bipolar disorders (BD). Machine learning/pattern recognition allows us to estimate the biological age of the brain from structural magnetic resonance imaging scans (MRI). The discrepancy between brain and chronological age could contribute to early detection and differentiation of BD and schizophrenia. We estimated brain age in 2 studies focusing on early stages of schizophrenia or BD. In the first study, we recruited 43 participants with first episode of schizophrenia-spectrum disorders (FES) and 43 controls. In the second study, we included 96 offspring of bipolar parents (48 unaffected, 48 affected) and 60 controls. We used relevance vector regression trained on an independent sample of 504 controls to estimate the brain age of study participants from structural MRI. We calculated the brain-age gap estimate (BrainAGE) score by subtracting the chronological age from the brain age. Participants with FES had higher BrainAGE scores than controls (F(1, 83) = 8.79, corrected P = .008, Cohen's d = 0.64). Their brain age was on average 2.64 ± 4.15 years greater than their chronological age (matched t(42) = 4.36, P stages of BD showed comparable BrainAGE scores to controls (F(2,149) = 1.04, corrected P = .70, η2 = 0.01) and comparable brain and chronological age. Early stages of schizophrenia, but not early stages of BD, were associated with advanced BrainAGE scores. Participants with FES showed neurostructural alterations, which made their brains appear 2.64 years older than their chronological age. BrainAGE scores could aid in early differential diagnosis between BD and schizophrenia. © The Author(s) 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com

Early-adult outcome of child and adolescent mental disorders as evidenced by a national-based case register survey

DEFF Research Database (Denmark)

Castagnini, Augusto; Foldager, Leslie; Caffo, Ernesto

2016-01-01

Background Mental disorders show varying degrees of continuity from childhood to adulthood. This study addresses the relationship of child and adolescent mental disorders to early adult psychiatric morbidity. Methods From a population at risk of 830,819 children and adolescents aged 6–16 years, we...... and substance use disorders. Conclusions These findings suggest that individuals with psychiatric antecedents in childhood and adolescence had a high risk of being referred for treatment in early adulthood, and many mental disorders for which they required treatment revealed both homotypic and heterotypic...

Self-differentiation and eating disorders in early and middle adolescence: A cross-sectional path analysis.

Science.gov (United States)

Doba, Karyn; Berna, Guillaume; Constant, Emilie; Nandrino, Jean-Louis

2018-03-07

This study examines the impact of self-differentiation, alexithymia and psychological distress on eating disorder symptoms in young and middle adolescence. Four hundred fifty-one adolescents completed self-report measures. Early and middle adolescents were categorized into two groups (12-14 years and 15-17 years) to represent distinct developmental stages. Significant differences were found between younger and older adolescents. The association between low self-differentiation and both eating disorders symptoms and psychological dimensions related to eating attitudes was stronger in early adolescence than in middle adolescence. The association between low self-differentiation and eating disorder symptoms was mediated by alexithymia and psychological distress in middle adolescence. Taken together, these findings suggest that self-differentiation could be useful in understanding psychological distress and alexithymia in eating disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effectiveness of Prescription-Based CNS Stimulants on Hospitalization in Patients With Schizophrenia

DEFF Research Database (Denmark)

Rohde, Christopher; Polcwiartek, Christoffer; Asztalos, Marton

2018-01-01

were used to investigate the effectiveness of CNS stimulants in patients with schizophrenia between 1995 and 2014; a mirror-image model with 605 individuals, using paired t tests and Wilcoxon signed rank tests, and a follow-up study with 789 individuals, using a conditional risk-set model. RESULTS: CNS...

Oppositional behavior and longitudinal predictions of early adulthood mental health problems in chronic tic disorders.

Science.gov (United States)

Thériault, Marie-Claude G; Bécue, Jean-Cyprien; Lespérance, Paul; Chouinard, Sylvain; Rouleau, Guy A; Richer, Francois

2018-03-16

Chronic tic disorders (TD) are associated with a number of psychological problems such as attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive behavior (OCB), oppositional-defiant disorder (ODD) as well as anxious and depressive symptoms. ODD is often considered a risk factor for many psychological symptoms and recent work suggests that different ODD dimensions show independent predictions of later psychological problems. This study examined the longitudinal predictions between ODD dimensions of Irritability and Defiance and the most frequent comorbidities in TD from childhood to early adulthood. From an initial sample of 135, parent reports were obtained on 58 participants with TD using standard clinical questionnaires and semi-structured interviews. Defiance symptoms decreased from baseline to follow-up whereas Irritability symptoms were more stable over time. In multiple regressions, Irritability in childhood predicted anxiety and OCB in early adulthood while Defiance in childhood predicted ADHD and conduct disorder symptoms in early adulthood. No developmental link was found for depressive symptoms. Results indicate that ODD dimensions are developmentally linked to both internalizing and externalizing adult mental health symptoms in TD. Copyright © 2018. Published by Elsevier B.V.

Early diagnosis and Early Start Denver Model intervention in autism spectrum disorders delivered in an Italian Public Health System service

Directory of Open Access Journals (Sweden)

Devescovi R

2016-06-01

Full Text Available Raffaella Devescovi,1 Lorenzo Monasta,2 Alice Mancini,3 Maura Bin,1 Valerio Vellante,1 Marco Carrozzi,1 Costanza Colombi4 1Division of Child Neurology and Psychiatry, 2Clinical Epidemiology and Public Health Research Unit, Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, 3Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 4Department of Psychiatry, University of Michigan Health System, Ann Arbor, MI, USA Background: Early diagnosis combined with an early intervention program, such as the Early Start Denver Model (ESDM, can positively influence the early natural history of autism spectrum disorders. This study evaluated the effectiveness of an early ESDM-inspired intervention, in a small group of toddlers, delivered at low intensity by the Italian Public Health System.Methods: Twenty-one toddlers at risk for autism spectrum disorders, aged 20–36 months, received 3 hours/wk of one-to-one ESDM-inspired intervention by trained therapists, combined with parents’ and teachers’ active engagement in ecological implementation of treatment. The mean duration of treatment was 15 months. Cognitive and communication skills, as well as severity of autism symptoms, were assessed by using standardized measures at pre-intervention (Time 0 [T0]; mean age =27 months and post-intervention (Time 1 [T1]; mean age =42 months.Results: Children made statistically significant improvements in the language and cognitive domains, as demonstrated by a series of nonparametric Wilcoxon tests for paired data. Regarding severity of autism symptoms, younger age at diagnosis was positively associated with greater improvement at post-assessment.Conclusion: Our results are consistent with the literature that underlines the importance of early diagnosis and early intervention, since prompt diagnosis can reduce the severity of autism symptoms and improve cognitive and language skills in younger children

Longitudinal follow-up to evaluate speech disorders in early-treated patients with infantile-onset Pompe disease.

Science.gov (United States)

Zeng, Yin-Ting; Hwu, Wuh-Liang; Torng, Pao-Chuan; Lee, Ni-Chung; Shieh, Jeng-Yi; Lu, Lu; Chien, Yin-Hsiu

2017-05-01

Patients with infantile-onset Pompe disease (IOPD) can be treated by recombinant human acid alpha glucosidase (rhGAA) replacement beginning at birth with excellent survival rates, but they still commonly present with speech disorders. This study investigated the progress of speech disorders in these early-treated patients and ascertained the relationship with treatments. Speech disorders, including hypernasal resonance, articulation disorders, and speech intelligibility, were scored by speech-language pathologists using auditory perception in seven early-treated patients over a period of 6 years. Statistical analysis of the first and last evaluations of the patients was performed with the Wilcoxon signed-rank test. A total of 29 speech samples were analyzed. All the patients suffered from hypernasality, articulation disorder, and impairment in speech intelligibility at the age of 3 years. The conditions were stable, and 2 patients developed normal or near normal speech during follow-up. Speech therapy and a high dose of rhGAA appeared to improve articulation in 6 of the 7 patients (86%, p = 0.028) by decreasing the omission of consonants, which consequently increased speech intelligibility (p = 0.041). Severity of hypernasality greatly reduced only in 2 patients (29%, p = 0.131). Speech disorders were common even in early and successfully treated patients with IOPD; however, aggressive speech therapy and high-dose rhGAA could improve their speech disorders. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Drug Elucidation: Invertebrate Genetics Sheds New Light on the Molecular Targets of CNS Drugs

Directory of Open Access Journals (Sweden)

Donard S. Dwyer

2014-07-01

Full Text Available Many important drugs approved to treat common human diseases were discovered by serendipity, without a firm understanding of their modes of action. As a result, the side effects and interactions of these medications are often unpredictable, and there is limited guidance for improving the design of next-generation drugs. Here, we review the innovative use of simple model organisms, especially Caenorhabditis elegans, to gain fresh insights into the complex biological effects of approved CNS medications. Whereas drug discovery involves the identification of new drug targets and lead compounds/biologics, and drug development spans preclinical testing to FDA approval, drug elucidation refers to the process of understanding the mechanisms of action of marketed drugs by studying their novel effects in model organisms. Drug elucidation studies have revealed new pathways affected by antipsychotic drugs, e.g., the insulin signaling pathway, a trace amine receptor and a nicotinic acetylcholine receptor. Similarly, novel targets of antidepressant drugs and lithium have been identified in C. elegans, including lipid-binding/transport proteins and the SGK-1 signaling pathway, respectively. Elucidation of the mode of action of anesthetic agents has shown that anesthesia can involve mitochondrial targets, leak currents and gap junctions. The general approach reviewed in this article has advanced our knowledge about important drugs for CNS disorders and can guide future drug discovery efforts.

Current approaches to enhance CNS delivery of drugs across the brain barriers

Directory of Open Access Journals (Sweden)

Lu CT

2014-05-01

Full Text Available Cui-Tao Lu,1 Ying-Zheng Zhao,2,3 Ho Lun Wong,4 Jun Cai,5 Lei Peng,2 Xin-Qiao Tian1 1The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of China; 2Hainan Medical College, Haikou City, Hainan Province, People’s Republic of China; 3College of Pharmaceutical Sciences, Wenzhou Medical University, Zhejiang Province, People’s Republic of China; 4School of Pharmacy, Temple University, Philadelphia, PA, USA; 5Departments of Pediatrics and Anatomical Sciences and Neurobiology, University of Louisville School of Medicine Louisville, KY, USA Abstract: Although many agents have therapeutic potentials for central nervous system (CNS diseases, few of these agents have been clinically used because of the brain barriers. As the protective barrier of the CNS, the blood–brain barrier and the blood–cerebrospinal fluid barrier maintain the brain microenvironment, neuronal activity, and proper functioning of the CNS. Different strategies for efficient CNS delivery have been studied. This article reviews the current approaches to open or facilitate penetration across these barriers for enhanced drug delivery to the CNS. These approaches are summarized into three broad categories: noninvasive, invasive, and miscellaneous techniques. The progresses made using these approaches are reviewed, and the associated mechanisms and problems are discussed. Keywords: drug delivery system, blood–brain barrier (BBB, central nervous system, brain-targeted therapy, cerebrospinal fluid (CSF

TRPM2 Channel Aggravates CNS Inflammation and Cognitive Impairment via Activation of Microglia in Chronic Cerebral Hypoperfusion.

Science.gov (United States)

Miyanohara, Jun; Kakae, Masashi; Nagayasu, Kazuki; Nakagawa, Takayuki; Mori, Yasuo; Arai, Ken; Shirakawa, Hisashi; Kaneko, Shuji

2018-04-04

Chronic cerebral hypoperfusion is a characteristic seen in widespread CNS diseases, including neurodegenerative and mental disorders, and is commonly accompanied by cognitive impairment. Recently, several studies demonstrated that chronic cerebral hypoperfusion can induce the excessive inflammatory responses that precede neuronal dysfunction; however, the precise mechanism of cognitive impairment due to chronic cerebral hypoperfusion remains unknown. Transient receptor potential melastatin 2 (TRPM2) is a Ca 2+ -permeable channel that is abundantly expressed in immune cells and is involved in aggravation of inflammatory responses. Therefore, we investigated the pathophysiological role of TRPM2 in a mouse chronic cerebral hypoperfusion model with bilateral common carotid artery stenosis (BCAS). When male mice were subjected to BCAS, cognitive dysfunction and white matter injury at day 28 were significantly improved in TRPM2 knock-out (TRPM2-KO) mice compared with wild-type (WT) mice, whereas hippocampal damage was not observed. There were no differences in blood-brain barrier breakdown and H 2 O 2 production between the two genotypes at 14 and 28 d after BCAS. Cytokine production was significantly suppressed in BCAS-operated TRPM2-KO mice compared with WT mice at day 28. In addition, the number of Iba1-positive cells gradually decreased from day 14. Moreover, daily treatment with minocycline significantly improved cognitive perturbation. Surgical techniques using bone marrow chimeric mice revealed that activated Iba1-positive cells in white matter could be brain-resident microglia, not peripheral macrophages. Together, these findings suggest that microglia contribute to the aggravation of cognitive impairment by chronic cerebral hypoperfusion, and that TRPM2 may be a potential target for chronic cerebral hypoperfusion-related disorders. SIGNIFICANCE STATEMENT Chronic cerebral hypoperfusion is manifested in a wide variety of CNS diseases, including neurodegenerative

EEG Analytics for Early Detection of Autism Spectrum Disorder: A data-driven approach.

Science.gov (United States)

Bosl, William J; Tager-Flusberg, Helen; Nelson, Charles A

2018-05-01

Autism spectrum disorder (ASD) is a complex and heterogeneous disorder, diagnosed on the basis of behavioral symptoms during the second year of life or later. Finding scalable biomarkers for early detection is challenging because of the variability in presentation of the disorder and the need for simple measurements that could be implemented routinely during well-baby checkups. EEG is a relatively easy-to-use, low cost brain measurement tool that is being increasingly explored as a potential clinical tool for monitoring atypical brain development. EEG measurements were collected from 99 infants with an older sibling diagnosed with ASD, and 89 low risk controls, beginning at 3 months of age and continuing until 36 months of age. Nonlinear features were computed from EEG signals and used as input to statistical learning methods. Prediction of the clinical diagnostic outcome of ASD or not ASD was highly accurate when using EEG measurements from as early as 3 months of age. Specificity, sensitivity and PPV were high, exceeding 95% at some ages. Prediction of ADOS calibrated severity scores for all infants in the study using only EEG data taken as early as 3 months of age was strongly correlated with the actual measured scores. This suggests that useful digital biomarkers might be extracted from EEG measurements.

Combined small-molecule inhibition accelerates the derivation of functional, early-born, cortical neurons from human pluripotent stem cells

Science.gov (United States)

Qi, Yuchen; Zhang, Xin-Jun; Renier, Nicolas; Wu, Zhuhao; Atkin, Talia; Sun, Ziyi; Ozair, M. Zeeshan; Tchieu, Jason; Zimmer, Bastian; Fattahi, Faranak; Ganat, Yosif; Azevedo, Ricardo; Zeltner, Nadja; Brivanlou, Ali H.; Karayiorgou, Maria; Gogos, Joseph; Tomishima, Mark; Tessier-Lavigne, Marc; Shi, Song-Hai; Studer, Lorenz

2017-01-01

Considerable progress has been made in converting human pluripotent stem cells (hPSCs) into functional neurons. However, the protracted timing of human neuron specification and functional maturation remains a key challenge that hampers the routine application of hPSC-derived lineages in disease modeling and regenerative medicine. Using a combinatorial small-molecule screen, we previously identified conditions for the rapid differentiation of hPSCs into peripheral sensory neurons. Here we generalize the approach to central nervous system (CNS) fates by developing a small-molecule approach for accelerated induction of early-born cortical neurons. Combinatorial application of 6 pathway inhibitors induces post-mitotic cortical neurons with functional electrophysiological properties by day 16 of differentiation, in the absence of glial cell co-culture. The resulting neurons, transplanted at 8 days of differentiation into the postnatal mouse cortex, are functional and establish long-distance projections, as shown using iDISCO whole brain imaging. Accelerated differentiation into cortical neuron fates should facilitate hPSC-based strategies for disease modeling and cell therapy in CNS disorders. PMID:28112759

Risk factors for early treatment discontinuation in patients with obsessive-compulsive disorder

Directory of Open Access Journals (Sweden)

Juliana Belo Diniz

2011-01-01

Full Text Available INTRODUCTION: In obsessive-compulsive disorder, early treatment discontinuation can hamper the effectiveness of first-line treatments. OBJECTIVE: This study aimed to investigate the clinical correlates of early treatment discontinuation among obsessive-compulsive disorder patients. METHODS: A group of patients who stopped taking selective serotonin reuptake inhibitors (SSRIs or stopped participating in cognitive behavioral therapy before completion of the first twelve weeks (total n = 41; n = 16 for cognitive behavioral therapy and n = 25 for SSRIs were compared with a paired sample of compliant patients (n = 41. Demographic and clinical characteristics were obtained at baseline using structured clinical interviews. Chisquare and Mann-Whitney tests were used when indicated. Variables presenting a p value <0.15 for the difference between groups were selected for inclusion in a logistic regression analysis that used an interaction model with treatment dropout as the response variable. RESULTS: Agoraphobia was only present in one (2.4% patient who completed the twelve-week therapy, whereas it was present in six (15.0% patients who dropped out (p = 0.044. Social phobia was present in eight (19.5% patients who completed the twelve-week therapy and eighteen (45% patients who dropped out (p = 0.014. Generalized anxiety disorder was present in eight (19.5% patients who completed the twelve-week therapy and twenty (50% dropouts (p = 0.004, and somatization disorder was not present in any of the patients who completed the twelveweek therapy; however, it was present in six (15% dropouts (p = 0.010. According to the logistic regression model, treatment modality (p = 0.05, agoraphobia, the Brown Assessment of Beliefs Scale scores (p = 0.03 and the Beck Anxiety Inventory (p = 0.02 scores were significantly associated with the probability of treatment discontinuation irrespective of interactions with other variables. DISCUSSION AND CONCLUSION: Early treatment

Association of Tic Disorders and Enterovirus Infection: A Nationwide Population-Based Study.

Science.gov (United States)

Tsai, Ching-Shu; Yang, Yao-Hsu; Huang, Kuo-You; Lee, Yena; McIntyre, Roger S; Chen, Vincent Chin-Hung

2016-04-01

There has been growing interest in the association between infectious disease and mental disorders, but an association between enterovirus (EV) infection and tic disorders has not been sufficiently explored. Herein, we aim to investigate the association between EV infection and incidence of tic disorders in a nationwide population-based sample using Taiwan's National Health Insurance Research Database. We identified individuals aged ≤18 years prior to 2005 with an inpatient diagnosis of EV infection and/or history of EV infection. Tic disorder was operationalized using International Classification of Disease, Revision 9, Clinical Modification (ICD-9-CM) codes 307.20-307.23. A total of 47,998 individuals with history of EV infection were compared to 47,998 sex-, age-, and urbanization-matched controls on incidence of tic disorders. The mean ± standard deviation follow-up period for all subjects was 9.7 ± 3.6 years; the mean latency period between initial EV infection and incident diagnosis of tic disorder diagnosis was 5.4 ± 2.8 years. EV infection was significantly associated with greater incidence of tic disorders (hazard ratio [HR] = 1.24, 95% CI: 1.07-1.45). When subgrouped on the basis of central nervous system (CNS) involvement, EV infection with CNS involvement was not significantly associated with greater incidence of tic disorders when compared to controls (HR = 1.25, 95% CI: 0.64-2.43); EV infection without CNS involvement was significantly associated greater incidence of tic disorders when compared to controls (HR = 1.24, 95% CI: 1.07-1.45). In addition, hospitalization for an EV infection did not increase the hazard for greater incidence of tic disorders (HR = 1.32, 95% CI: 1.04-1.67 with hospitalization and 1.22, 95% CI: 1.04-1.44 without hospitalization). EV infection is temporally associated with incidence of tic disorders. Our observations add to the growing body of literature implicating immune-inflammatory system in

Parental death and bipolar disorder: a robust association was found in early maternal suicide

DEFF Research Database (Denmark)

Tsuchiya, Kenji; Agerbo, Esben; Mortensen, Preben Bo

2005-01-01

of a conditional logistic regression analysis. RESULTS: Among 947 subjects with bipolar disorder and 47,350 controls, those having experienced the parental suicide were significantly associated with an increased risk for BPD (incidence rate ratios: 1.83 [95% confidence interval: 1.07 to 3.12] for paternal suicide......BACKGROUND: Previous studies have suggested that early parental death may be associated with the emergence of bipolar disorder in later life. However, it remains unknown whether this association applies specifically to parental death due to suicide or only to early parental death. The present study...... were born in 1960 or later and were first admitted to or had first contact with Danish psychiatric facilities between 1981 and 1998 with a diagnosis of bipolar disorder, and fifty age-matched controls per case were extracted. The effects of the deaths of relatives were estimated by means...

Radioprotection of mouse CNS endothelial cells in vivo

International Nuclear Information System (INIS)

Lyubimova, N.; Coultas, P.; Martin, R.

1996-01-01

Full text: Radioprotection using the minor groove binding DNA ligand Hoechst 33342 has been demonstrated in vitro, and more recently in vivo, in mouse lung. Intravenous administration was used for the lung studies, and both endothelial and alveolar epithelial cells-showed good up-take. Radiation damage to the endothelial cell population has also been postulated as important in late developing radionecrosis of spinal cord and brain. Endothelial cell density in brain can be readily determined by a fluorescent-histochemical technique. Treatment with a monoamine oxidase inhibitor and subsequent injection with L-DOPA results in an accumulation of dopamine (DA) in CNS endothelial cells. DA is converted to a fluorophore by exposure to paraformaldehyde, and cell numbers assayed by fluorescence microscopy. Earlier studies used this technique to monitor post-irradiation changes in endothelial cell density in rodent brain and showed the loss, within 24 hours, of a sensitive subpopulation comprising about 15% of the endothelial cells. Ten minutes after intravenous injection of Hoechst 33342 (80mg/kg) the ligand is confined by its limited penetration to the endothelial cells in mouse brain. When we irradiated at this time, there was protection against early endothelial cell loss. Ablation of the sensitive subpopulation in unprotected mice takes place over a dose range of 1 to 3 Gy γ-rays, but doses between 12 to 20 Gy are required in the presence of ligand. This protection equates to a very high dose modification factor of about 7 and possibly reflects a suppression of apoptosis in the sensitive endothelial subpopulation. The extent to which there is enhanced survival in the endothelial population as a whole and how the observed protection affects late CNS necrosis development has yet to be determined. However present results clearly show potential for the use of DNA-binding radioprotectors with limited penetration for investigations into the relative significance of

Nootropic, anxiolytic and CNS-depressant studies on different plant sources of shankhpushpi.

Science.gov (United States)

Malik, Jai; Karan, Maninder; Vasisht, Karan

2011-12-01

Shankhpushpi, a well-known drug in Ayurveda, is extensively used for different central nervous system (CNS) effects especially memory enhancement. Different plants are used under the name shankhpushpi in different regions of India, leading to an uncertainty regarding its true source. Plants commonly used under the name shankhpushpi are: Convolvulus pluricaulis Chois., Evolvulus alsinoides Linn., both from Convolvulaceae, and Clitoria ternatea Linn. (Leguminosae). To find out the true source of shankhpushpi by evaluating and comparing memory-enhancing activity of the three above mentioned plants. Anxiolytic, antidepressant and CNS-depressant activities of these three plants were also compared and evaluated. The nootropic activity of the aqueous methanol extract of each plant was tested using elevated plus-maze (EPM) and step-down models. Anxiolytic, antidepressant and CNS-depressant studies were evaluated using EPM, Porsolt?s swim despair and actophotometer models, respectively. C. pluricaulis extract (CPE) at a dose of 100 mg/kg, p.o. showed maximum nootropic and anxiolytic activity (p nootropic, anxiolytic and CNS-depressant activity. The results of memory-enhancing activity suggest C. pluricaulis to be used as true source of shankhpushpi.

Glucocorticoid treatment of MCMV infected newborn mice attenuates CNS inflammation and limits deficits in cerebellar development.

Directory of Open Access Journals (Sweden)

Kate Kosmac

2013-03-01

Full Text Available Infection of the developing fetus with human cytomegalovirus (HCMV is a major cause of central nervous system disease in infants and children; however, mechanism(s of disease associated with this intrauterine infection remain poorly understood. Utilizing a mouse model of HCMV infection of the developing CNS, we have shown that peripheral inoculation of newborn mice with murine CMV (MCMV results in CNS infection and developmental abnormalities that recapitulate key features of the human infection. In this model, animals exhibit decreased granule neuron precursor cell (GNPC proliferation and altered morphogenesis of the cerebellar cortex. Deficits in cerebellar cortical development are symmetric and global even though infection of the CNS results in a non-necrotizing encephalitis characterized by widely scattered foci of virus-infected cells with mononuclear cell infiltrates. These findings suggested that inflammation induced by MCMV infection could underlie deficits in CNS development. We investigated the contribution of host inflammatory responses to abnormal cerebellar development by modulating inflammatory responses in infected mice with glucocorticoids. Treatment of infected animals with glucocorticoids decreased activation of CNS mononuclear cells and expression of inflammatory cytokines (TNF-α, IFN-β and IFNγ in the CNS while minimally impacting CNS virus replication. Glucocorticoid treatment also limited morphogenic abnormalities and normalized the expression of developmentally regulated genes within the cerebellum. Importantly, GNPC proliferation deficits were normalized in MCMV infected mice following glucocorticoid treatment. Our findings argue that host inflammatory responses to MCMV infection contribute to deficits in CNS development in MCMV infected mice and suggest that similar mechanisms of disease could be responsible for the abnormal CNS development in human infants infected in-utero with HCMV.

The shifting landscape of metastatic breast cancer to the CNS.

Science.gov (United States)

Quigley, Matthew R; Fukui, Olivia; Chew, Brandon; Bhatia, Sanjay; Karlovits, Steven

2013-07-01

The improved survival following the diagnosis of breast cancer has potentially altered the characteristics and course of patients presenting with CNS involvement. We therefore sought to define our current cohort of breast cancer patients with metastatic disease to the CNS in regard to modern biomarkers and clinical outcome. Review of clinical and radiographic records of women presenting to a tertiary medical center with the new diagnosis of CNS metastatic disease from breast cancer. This was a retrospective review from patients identities obtained from two prospective databases. There were 88 women analyzed who were treated over the period of January 2003 to February 2010, average age 56.9 years. At the time of initial presentation of CNS disease, 68 % of patients had multiple brain metastases, 17 % had a solitary metastasis, and 15 % had only leptomeningeal disease (LMD). The median survival for all patients from the time of diagnosis of breast disease was 50.0 months, and 9.7 months from diagnosis of CNS involvement. The only factor related to overall survival was estrogen receptor-positive pathology (57.6 v. 38.2 months, p = .02 log-rank); those related to survival post CNS diagnosis were presentation with LMD (p = .004, HR = 3.1, Cox regression) and triple-negative hormonal/HER2 status (p = .02, HR = 2.3, Cox regression). Patients with either had a median survival of 3.1 months (no patients in common). Of the 75 patients who initially presented with metastatic brain lesions, 20 (26 %) subsequently developed LMD in the course of their disease (median 10.4 months), following which survival was grim (1.8 months median). Symptoms of LMD were most commonly lower extremity weakness (14/33), followed by cranial nerve deficits (11/33). The recently described Graded Prognostic Assessment (GPA) tumor index stratified median survival at 2.5, 5.9, 13.1, and 21.7 months, respectively, for indices of 1-4 (p = .004, log-rank), which

CBT for eating disorders: The impact of early changes in eating pathology on later changes in personality pathology, anxiety and depression.

Science.gov (United States)

Turner, Hannah; Marshall, Emily; Wood, Francesca; Stopa, Lusia; Waller, Glenn

2016-02-01

Whilst studies have consistently identified early symptom reduction as an important predictor of treatment outcome, the impact of early change on common comorbid features has not been investigated. This study of CBT for eating disorders explored patterns of early change in eating pathology and longer-term change in personality pathology, anxiety and depression. It also explored the impact of early change in eating pathology on overall change in personality pathology, anxiety and depression. Participants were 179 adults diagnosed with eating disorders who were offered a course of CBT in an out-patient community eating disorders service in the UK. Patients completed a measure of eating disorder psychopathology at the start of treatment and following the 6th session. They also completed measures of personality disorder cognitions, anxiety and depression at the start and end of treatment. There were significant changes in eating pathology over the first six sessions of treatment. Significant improvements were also seen in personality disorder pathology, anxiety and depression by the end of therapy. Effect sizes were medium to large for both completer and intention to treat analyses. Early changes in eating pathology were associated with later changes in common comorbid features, with early reduction in restraint being a key predictor. These findings demonstrate that early symptom change can be achieved in CBT for eating disorders when delivered in routine clinical practice. Such change has long-term benefits that go beyond the domain of eating pathology, enhancing change in personality pathology, anxiety and depression. Copyright © 2015 Elsevier Ltd. All rights reserved.

A categorical view toward diagnosis and classification of war-related psychiatric disorders

Directory of Open Access Journals (Sweden)

Abhari SA

1993-04-01

Full Text Available Documented war experiences have provided early descriptions of different group of psychiatric features. A combat soldier with palpitation and chest pains was felt to have a functional cardiac disturbance, called soldier's heart. Anxiety and other symptoms indicating increased arousal were called shell shock and were thought to be related to lesions in the central nervous system (CNS. Describing analytically war events could operate with an enormous emotional intensity breaking through the ego defences and flooding it with an uncontrollable anxiety. Post traumatic stress disorder (PTSD delineates a syndrome developing after a discrete traumatic event in a stress setting. Diagnostic conceptualization which tie PTSD to stress and trauma invariably involve two different approaches from two different theoretical bases: the concepts dealing with trauma on the one hand (which could effect on CNS and those dealing with stress-response theory on the other. Author emphasizes on viewing the patients who complain of war psychiatric effects in three categories: (1 Non PTSD diagnoses that the patient ought to be treated accordingly (2 Traumatic neurosis which has overwhelming war stress related emotional aspects and is occurred in predisposed individuals. This category is suggested to be classified as post war stress disorder specifically, to be differentiated from other post traumatic psychiatric categories. (3 Author also suggests the third category as post traumatic war stress syndrome which is thought to have organic origin. Symptoms such as hyperacusis, hyperirritability, tinnitus and particular type of head aches which are mostly refractory to treatment confirm the hypothesis.

Developmentally Sensitive Diagnostic Criteria for Mental Health Disorders in Early Childhood: The Diagnostic and Statistical Manual of Mental Disorders-IV, the Research Diagnostic Criteria-Preschool Age, and the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood-Revised

Science.gov (United States)

Egger, Helen L.; Emde, Robert N.

2011-01-01

As the infant mental health field has turned its focus to the presentation, course, and treatment of clinically significant mental health disorders, the need for reliable and valid criteria for identifying and assessing mental health symptoms and disorders in early childhood has become urgent. In this article we offer a critical perspective on…

Psychiatric Disorders and Predictors Hereof Among Refugee Children in Early Adulthood

DEFF Research Database (Denmark)

Barghadouch, Amina; Carlsson, Jessica; Norredam, Marie

2018-01-01

Studies show a high level of mental health problems among refugee children and adults. This study aimed to examine psychiatric disorders among refugee children in early adulthood. A total of 15,264 young adult refugees, who obtained residence permission January 1, 1993 to December 31, 2010, were...... matched 1:6 on age and sex with 99,313 Danish-born children. Rate ratios (RR) of having a first-time in- or outpatient hospital diagnosis with an affective (F30-39), psychotic (F29-30), neurotic (F40-48), or any psychiatric disorder (F00-99) according to ICD-10 were computed. Refugees had higher RRs...... of psychotic (RR: 1.81, 95%CI: 1.41-2.32) and nervous (RR: 1.28, 95% CI: 1.14-1.43) disorders compared with Danish-born children. The RRs of having an affective disorder among refugees was 0.74 (95% CI: 0.60-0.90) compared with Danish-born children. Sex, geographical origin, migrant status, household income...

CD11c(hi) Dendritic Cells Regulate Ly-6C(hi) Monocyte Differentiation to Preserve Immune-privileged CNS in Lethal Neuroinflammation.

Science.gov (United States)

Kim, Jin Hyoung; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Patil, Ajit Mahadev; Han, Young Woo; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; Eo, Seong Kug

2015-12-02

Although the roles of dendritic cells (DCs) in adaptive defense have been defined well, the contribution of DCs to T cell-independent innate defense and subsequent neuroimmunopathology in immune-privileged CNS upon infection with neurotropic viruses has not been completely defined. Notably, DC roles in regulating innate CD11b(+)Ly-6C(hi) monocyte functions during neuroinflammation have not yet been addressed. Using selective ablation of CD11c(hi)PDCA-1(int/lo) DCs without alteration in CD11c(int)PDCA-1(hi) plasmacytoid DC number, we found that CD11c(hi) DCs are essential to control neuroinflammation caused by infection with neurotropic Japanese encephalitis virus, through early and increased infiltration of CD11b(+)Ly-6C(hi) monocytes and higher expression of CC chemokines. More interestingly, selective CD11c(hi) DC ablation provided altered differentiation and function of infiltrated CD11b(+)Ly-6C(hi) monocytes in the CNS through Flt3-L and GM-CSF, which was closely associated with severely enhanced neuroinflammation. Furthermore, CD11b(+)Ly-6C(hi) monocytes generated in CD11c(hi) DC-ablated environment had a deleterious rather than protective role during neuroinflammation, and were more quickly recruited into inflamed CNS, depending on CCR2, thereby exacerbating neuroinflammation via enhanced supply of virus from the periphery. Therefore, our data demonstrate that CD11c(hi) DCs provide a critical and unexpected role to preserve the immune-privileged CNS in lethal neuroinflammation via regulating the differentiation, function, and trafficking of CD11b(+)Ly-6C(hi) monocytes.

Effects of comorbidity and early age of onset in young people with Bipolar Disorder on self harming behaviour and suicide attempts.

Science.gov (United States)

Moor, Stephanie; Crowe, Marie; Luty, Sue; Carter, Janet; Joyce, Peter R

2012-02-01

The age of the first episode of illness in Bipolar Disorder has been shown to be an important predictor of outcome with early onset, particularly onset before puberty, associated with greater comorbidity, a poorer quality of life and greatest impairment in functioning. Baseline data from a psychotherapy study was used to examine the prevalence of other comorbid psychiatric conditions and the impact of onset at an early age on both self harming behaviour and suicide attempts in young people with Bipolar Disorder. This study of 100 adolescents and young adults (aged 15-36 years) with Bipolar Disorder showed that comorbid conditions were very common, even at the start of their bipolar illness. Comorbidity increased as the age of onset decreased with very early onset (self harmed and attempted suicide with high lethal intent. Self harming behaviour was predicted by having a lifetime diagnoses of Borderline Personality Disorder and Panic Disorder along with an early age of onset of Bipolar Disorder. In contrast, previous suicide attempts were predicted by greater comorbidity and not by very early (<13 years) age of onset. Copyright © 2011 Elsevier B.V. All rights reserved.

Ketamine displaces the novel NMDA receptor SPET probe [123I]CNS-1261 in humans in vivo

International Nuclear Information System (INIS)

Stone, James M.; Erlandsson, Kjell; Arstad, Erik; Bressan, Rodrigo A.; Squassante, Lisa; Teneggi, Vincenza; Ell, Peter J.; Pilowsky, Lyn S.

2006-01-01

[ 123 I]CNS-1261 [N-(1-naphthyl)-N'-(3-iodophenyl)-N-methylguanidine] is a high-affinity SPET ligand with selectivity for the intrachannel PCP/ketamine/MK-801 site of the N-methyl-D-aspartate (NMDA) receptor. This study evaluated the effects of ketamine (a specific competitor for the intrachannel PCP/ketamine/MK-801 site) on [ 123 I]CNS-1261 binding to NMDA receptors in vivo. Ten healthy volunteers underwent 2 bolus-plus-infusion [ 123 I]CNS-1261 scans, one during placebo and the other during a ketamine challenge. Ketamine administration led to a significant decrease in [ 123 I]CNS-1261 V T in most of the brain regions examined (P 123 I]CNS-1261 appears to be a specific ligand in vivo for the intrachannel PCP/ketamine/MK-801 NMDA binding site

[11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter

DEFF Research Database (Denmark)

Vase, Karina Højrup; Peters, Dan; Nielsen, Elsebeth Ø

2014-01-01

-azabicyclo[3.2.1]octane (NS8880), targeting NET. NS8880 has an in vitro binding profile comparable to desipramine and is structurally not related to reboxetine. METHODS: Labeling of NS8880 with [11C] was achieved by a non-conventional technique: substitution of pyridinyl fluorine with [11C]methanolate...... yields with high purity. The PET in vivo evaluation in pig and rat revealed a rapid brain uptake of [11C]NS8880 and fast obtaining of equilibrium. Highest binding was observed in thalamic and hypothalamic regions. Pretreatment with desipramine efficiently reduced binding of [11C]NS8880. CONCLUSION: Based...... on the pre-clinical results obtained so far [11C]NS8880 displays promising properties for PET imaging of NET....

Interactions of the histamine and hypocretin systems in CNS disorders.

Science.gov (United States)

Shan, Ling; Dauvilliers, Yves; Siegel, Jerome M

2015-07-01

Histamine and hypocretin neurons are localized to the hypothalamus, a brain area critical to autonomic function and sleep. Narcolepsy type 1, also known as narcolepsy with cataplexy, is a neurological disorder characterized by excessive daytime sleepiness, impaired night-time sleep, cataplexy, sleep paralysis and short latency to rapid eye movement (REM) sleep after sleep onset. In narcolepsy, 90% of hypocretin neurons are lost; in addition, two groups reported in 2014 that the number of histamine neurons is increased by 64% or more in human patients with narcolepsy, suggesting involvement of histamine in the aetiology of this disorder. Here, we review the role of the histamine and hypocretin systems in sleep-wake modulation. Furthermore, we summarize the neuropathological changes to these two systems in narcolepsy and discuss the possibility that narcolepsy-associated histamine abnormalities could mediate or result from the same processes that cause the hypocretin cell loss. We also review the changes in the hypocretin and histamine systems, and the associated sleep disruptions, in Parkinson disease, Alzheimer disease, Huntington disease and Tourette syndrome. Finally, we discuss novel therapeutic approaches for manipulation of the histamine system.

Morphological evaluation of fetus CNS and its related anomalies

International Nuclear Information System (INIS)

Oi, Shizuo; Tamaki, Norihiko; Matsumoto, Satoshi; Katayama, Kazuaki; Mochizuki, Matsuto

1989-01-01

The fetus central nervous system was evaluated morphologically by ultrasonography (US), magnetic resonance imaging (MRI), and CT scan to analyze the prenatal diagnostic value for CNS anomalies. A total of 31 patients with 42 lesions had been diagnosed during the preceding 7 years. The patients included 24 with hydrocephalus, three with anencephaly, three with myeloschisis, three with holoprosencephaly, three with an encephalocele, two with a Dandy-Walker cyst, one with hydroencephalodysplasia, one with an intracranial neoplasm, one with sacrococcygeal teratoma, and one with sacral agenesis. Compared with US and MRI, CT proved to be more accurate in the detection of spine and cranium-bone morphology. This finding seems to be valuable in the diagnosis of spina bifida, cranium bifidum and some cases of hypertensive hydrocephalus, especially in the axial view. MRI was definitely superior in the anatomico-pathological diagnosis of cerebral dysgenesis, ventriculomegaly, intracranial tumors, and other brain parenchymal changes in view of multi-dimensional analysis. The most considerable disadvantage of MRI in the diagnosis of a fetus CNS anomaly is the poor information about spine and cranium morphology. A super-conducting MRI system is still insufficient to demonstrate the spinal cord of a fetus. US was routinely used, and the multidimensional slices were useful for screening the CNS abnormalies. Some of the fetus brain lesions, such as intracranial hematomas, had a specific echogenecity on US. However, US sometimes failed to demarcate the cerebral parenchymal or subdural morphological changes because its artifacts had hyperchoic shadows. While US, MRI, and CT were valuable diagnostic tools in the morphological evaluation of fetus CNS and its related anomalies, each modality has different diagnostic advantages and disadvantages. Improvement can be expected when these diagnostic imaging modalities are complementary, depending upon the nature of the anatomy. (J.P.N.)

Mood and anxiety disorders as early manifestations of medical illness: a systematic review.

Science.gov (United States)

Cosci, Fiammetta; Fava, Giovanni A; Sonino, Nicoletta

2015-01-01

Affective disturbances involving alterations of mood, anxiety and irritability may be early symptoms of medical illnesses. The aim of this paper was to provide a systematic review of the literature with qualitative data synthesis. MEDLINE, PsycINFO, EMBASE, Cochrane, and ISI Web of Science were systematically searched from inception to February 2014. Search terms were 'prodrome/early symptom', combined using the Boolean 'AND' operator with 'anxiety/depression/mania/hypomania/irritability/irritable mood/hostility', combined with the Boolean 'AND' operator with 'medical illness/medical disorder'. PRISMA guidelines were followed. A total of 21 studies met the inclusion criteria and were analyzed. Depression was found to be the most common affective prodrome of medical disorders and was consistently reported in Cushing's syndrome, hypothyroidism, hyperparathyroidism, pancreatic and lung cancer, myocardial infarction, Wilson's disease, and AIDS. Mania, anxiety and irritability were less frequent. Physicians may not pursue medical workup of cases that appear to be psychiatric in nature. They should be alerted that disturbances in mood, anxiety and irritability may antedate the appearance of a medical disorder.

Analysis of neurocognitive function and CNS endpoints in the PROTEA trial

DEFF Research Database (Denmark)

Clarke, Amanda; Johanssen, Veronika; Gerstoft, Jan

2014-01-01

INTRODUCTION: During treatment with protease inhibitor monotherapy, the number of antiretrovirals with therapeutic concentrations in the cerebrospinal fluid (CSF) is lower, compared to standard triple therapy. However, the clinical consequences are unclear. METHODS: A total of 273 patients with HIV...... and the Grooved Pegboard Test at screening, baseline and at Week 48. A global neurocognitive score (NPZ-5) was derived by averaging the standardized results of the five domains. In a central nervous system (CNS) sub-study (n=70), HIV RNA levels in the CNS were evaluated at baseline and Week 48. Clinical adverse...... events related to the CNS were collected at each visit. RESULTS: Patients were 83% male and 88% White, with median age 43 years. There were more patients with nadir CD4 count below 200 cells/µL in the DRV/r monotherapy arm (41/137, 30%) than the triple therapy arm (30/136, 22%). At Week 48...

Early diagnosis and Early Start Denver Model intervention in autism spectrum disorders delivered in an Italian Public Health System service.

Science.gov (United States)

Devescovi, Raffaella; Monasta, Lorenzo; Mancini, Alice; Bin, Maura; Vellante, Valerio; Carrozzi, Marco; Colombi, Costanza

2016-01-01

Early diagnosis combined with an early intervention program, such as the Early Start Denver Model (ESDM), can positively influence the early natural history of autism spectrum disorders. This study evaluated the effectiveness of an early ESDM-inspired intervention, in a small group of toddlers, delivered at low intensity by the Italian Public Health System. Twenty-one toddlers at risk for autism spectrum disorders, aged 20-36 months, received 3 hours/wk of one-to-one ESDM-inspired intervention by trained therapists, combined with parents' and teachers' active engagement in ecological implementation of treatment. The mean duration of treatment was 15 months. Cognitive and communication skills, as well as severity of autism symptoms, were assessed by using standardized measures at pre-intervention (Time 0 [T0]; mean age =27 months) and post-intervention (Time 1 [T1]; mean age =42 months). Children made statistically significant improvements in the language and cognitive domains, as demonstrated by a series of nonparametric Wilcoxon tests for paired data. Regarding severity of autism symptoms, younger age at diagnosis was positively associated with greater improvement at post-assessment. Our results are consistent with the literature that underlines the importance of early diagnosis and early intervention, since prompt diagnosis can reduce the severity of autism symptoms and improve cognitive and language skills in younger children. Particularly in toddlers, it seems that an intervention model based on the ESDM principles, involving the active engagement of parents and nursery school teachers, may be effective even when the individual treatment is delivered at low intensity. Furthermore, our study supports the adaptation and the positive impact of the ESDM entirely sustained by the Italian Public Health System.

Risk factors for suicide among children and youths with bipolar spectrum and early bipolar disorder.

Science.gov (United States)

Rajewska-Rager, Aleksandra; Sibilski, Piotr; Lepczyńska, Natalia

2015-01-01

In recent years much attention has been given to determine risk factors for suicide among adults with bipolar disorder. Such studies concerning children and youths, which would also take into account the specificity of the developmental age, are still too few. The ability to identify risk factors for children and youths with mood disorders, as well as the possibility to monitor them, is an essential element in preventing suicidal behaviours. Previous studies have clearly indicated that in the group of patients with an early onset of the bipolar disorder the occurrence of suicidal thoughts and intentions were significantly increased. Identifying the risk of suicide is hindered further by the complexity of the phenomenon, which is a compound interaction of various factors: biological, environmental, sociological, psychological and clinical. This is especially true with young adults suffering from mental illness and presenting a number of other psychopathological symptoms. The following paper introduces and reviews the results of current studies, which analysed the risk factors for suicide among children and youths with bipolar spectrum or already diagnosed with bipolar disorder. For this purpose we conducted the overview of recent years literature available in PubMed/MEDLINE database, including the following search criteria: early onset bipolar disorder, bipolar disorder in children and young people, the spectrum of bipolar disorder, and suicidal ideation, suicidal intent, suicide.

Advancing early detection of autism spectrum disorder by applying an integrated two-stage screening approach

NARCIS (Netherlands)

Oosterling, Iris J.; Wensing, Michel; Swinkels, Sophie H.; van der Gaag, Rutger Jan; Visser, Janne C.; Woudenberg, Tim; Minderaa, Ruud; Steenhuis, Mark-Peter; Buitelaar, Jan K.

Background: Few field trials exist on the impact of implementing guidelines for the early detection of autism spectrum disorders (ASD). The aims of the present study were to develop and evaluate a clinically relevant integrated early detection programme based on the two-stage screening approach of

SCREENING FOR EARLY DETECTION OF EATING DISORDERS

Directory of Open Access Journals (Sweden)

Elisaveta Pavlova

2016-12-01

Full Text Available Background: Eating Disorders (EDs are characterized by a persistent disturbance of eating or eating-related behavior that significantly impairs physical health or psychosocial functioning. EDs are caused by a complex interaction of genetic, biological, behavioral, psychological, and social factors. Their epidemiology is rising for the past decades, and EDs affect all races, social levels and both genders. Due to the long and expensive treatment, chronic course, and the fact that most of the sufferers do not realize the need for therapy or do not seek treatment, the demand on developing prevention programs, early detection and assessment is essential. Despite the fact, that many new EDs screening tools were developed already, there is a great lack of validated screening instruments, adapted to the Bulgarian conditions. Objects and methods: Our study aimed at eliciting a comprehensive battery for screening of not only specific ED pathology, but also some risk factors, such as negative body image, weight and depressive symptoms. The object of our study consisted of 201 females, aged 18 to 45 (mean 24.65. SCOOF- questionnaire, Eating Disorder Diagnostic Scale (EDDS-5, Body Image Questionnaire-34 and Beck Depression Inventory (BDI were applied. Results: Our preliminary results show that approximately 45% of the tested subjects show some of the: negative body image, eating disorders’ clinical pathology, distorted eating patterns, subclinical eating disorders pathology, overweight/obesity, or depressive symptoms. Conclusion: Our ongoing efforts in area of research also are aimed at developing and refining strategies for preventing and treating ED among adolescents and adults.

Nuclear innovation through collaboration. 35th Annual CNS conference and 39th CNS/CNA student conference

International Nuclear Information System (INIS)

2015-01-01

The Canadian Nuclear Society (CNS) held its 35th Annual Conference in Saint John, New Brunswick, Canada on May 31 to June 3, 2015, combined with the 39th Annual CNS/CNA Student Conference. With the theme of the conference, 'Nuclear Innovation through Collaboration', more than 425 delegates, exhibitors and students were in attendance. The conference commenced with two strong plenary sessions on Utility Collaborations to Improve Lifetime Performance; and, Performance Improvement Programs: Goals and Experience. The second day consisted of the panel discussions on International Developments in Used Nuclear Fuel Repository Programs, and two plenary sessions on: Enterprise Risk Management; and, Vendor Role in a Continuously Improving Industry. The third day contained a number of interesting features, including plenary sessions on Waste Management and Decommissioning; Developing Technologies and Resources, and a panel discussion on the Transportation of Used Nuclear Fuel. All three days of the conference also contained parallel sessions with over 100 technical papers presented at the main and student sessions. The technical session titles were: Refurbishment and Life Extension; Thermalhydraulics; Nuclear Materials; WMD - Radiation Monitoring; Safety and Licensing; Communication; Safety and Licensing; Instrumentation and Control; Advanced Reactor Designs; WMD - Deep Geological Repository Packaging; Reactor Physics; Chemistry and Materials; Advanced Fuel Cycles; Waste Management and Decommissioning; and, Medical Physics and Radiation Biology.

Metallothionein expression and roles in the CNS

DEFF Research Database (Denmark)

Penkowa, Milena

2002-01-01

  Metallothioneins (MTs) are low-molecular-weight (6-7 kDa) nonenzymatic proteins (60-68 amino acid residues, 25-30% being cysteine) expressed ubiquitous in the animal kingdom. In the central nervous system (CNS), three MT isoforms are known, namely MT-I to MT-III. MT-I and MT-II (MT...

Wilson?s disease presenting as rapid eye movement sleep behavior disorder: a possible window to early treatment

Directory of Open Access Journals (Sweden)

Gotthard G. Tribl

2014-09-01

Full Text Available Objective To describe characteristics of REM sleep behavior disorder in Wilson’s disease. Method Questionnaire-based interviews (patients and relatives, neurological examinations, two-week prospective dream-diary, video-polysomnography, transcranial sonography, MRI. Results Four Wilson’s disease cases with REM sleep behavior disorder were described; three had REM sleep behavior disorder as initial symptom. All showed mesencephalic tegmental/tectal sonographic hyperechogenicities and two presented ponto-mesencephalic tegmental MRI hyperintensities. Conclusion This first description of REM sleep behavior disorder in Wilson’s disease in literature documents REM sleep behavior disorder as a possible presenting symptom of Wilson’s disease and adds further evidence to the parallelism of Parkinson’s disease and Wilson’s disease in phenotype and brainstem topography, which ought to be further studied. REM sleep behavior disorder has prognostic relevance for neurodegeneration in α-synucleinopathies. In Wilson’s disease, usefulness of early diagnosis and treatment are already well established. REM sleep behavior disorder in Wilson’s disease offers a possible theoretical model for potential early treatment in this extrapyramidal and brainstem paradigm syndrome, previewing the possibility of neuroprotective treatment for REM sleep behavior disorder in “pre-clinical” Parkinson’s disease.

Is risk of central nervous system (CNS) relapse related to adjuvant taxane treatment in node-positive breast cancer? Results of the CNS substudy in the intergroup Phase III BIG 02-98 Trial

DEFF Research Database (Denmark)

Pestalozzi, B.C.; Francis, P.; Quinaux, E.

2008-01-01

BACKGROUND: Breast cancer central nervous system (CNS) metastases are an increasingly important problem because of high CNS relapse rates in patients treated with trastuzumab and/or taxanes. PATIENTS AND METHODS: We evaluated data from 2887 node-positive breast cancer patients randomised in the BIG...

Early-onset heroin use and its link to conduct disorder: Clinical and management challenges

Directory of Open Access Journals (Sweden)

Shobhit Jain

2016-01-01

Full Text Available Childhood substance abuse and delinquency often progress to harder substances and antisocial personality disorder and carries deleterious consequences for self, family and community at large. Early management of such cases poses several clinical and management challenges, as highlighted in the present case. The treatment seeking for this sub-population is very low in spite of community surveys showing a worrisome pattern of substance use among younger population. Further, very few specialty clinics and trained manpower exist in the country to manage early onset substance use. Whether conduct disorder be cause or consequence for drug use is debatable, in view of shared risk factors. The present case helps to understand need for comprehensive assessment for identifying risk factors and comorbid conditions. Only pharmacological management does not help, psychosocial management must be delivered. Several prevention strategies may also help if these risk factors are identified before progression to illicit substance use disorder.

The CNS connectome of a tadpole larva of Ciona intestinalis (L.) highlights sidedness in the brain of a chordate sibling.

Science.gov (United States)

Ryan, Kerrianne; Lu, Zhiyuan; Meinertzhagen, Ian A

2016-12-06

Left-right asymmetries in brains are usually minor or cryptic. We report brain asymmetries in the tiny, dorsal tubular nervous system of the ascidian tadpole larva, Ciona intestinalis . Chordate in body plan and development, the larva provides an outstanding example of brain asymmetry. Although early neural development is well studied, detailed cellular organization of the swimming larva's CNS remains unreported. Using serial-section EM we document the synaptic connectome of the larva's 177 CNS neurons. These formed 6618 synapses including 1772 neuromuscular junctions, augmented by 1206 gap junctions. Neurons are unipolar with at most a single dendrite, and few synapses. Some synapses are unpolarised, others form reciprocal or serial motifs; 922 were polyadic. Axo-axonal synapses predominate. Most neurons have ciliary organelles, and many features lack structural specialization. Despite equal cell numbers on both sides, neuron identities and pathways differ left/right. Brain vesicle asymmetries include a right ocellus and left coronet cells.

Brief Report: Agreement between Parents and Day-Care Professionals on Early Symptoms Associated with Autism Spectrum Disorders

Science.gov (United States)

Larsen, Kenneth; Aasland, Astrid; Diseth, Trond H.

2018-01-01

Early identification of Autism Spectrum Disorders (ASD) has the potential to elicit effective early intervention, improving children's level of functioning and developmental trajectories as well as reducing parental stress. Multiple sources of information, including several informants may facilitate early identification. This study examined the…

CDKL5 protein substitution therapy rescues neurological phenotypes of a mouse model of CDKL5 disorder.

Science.gov (United States)

Trazzi, Stefania; De Franceschi, Marianna; Fuchs, Claudia; Bastianini, Stefano; Viggiano, Rocchina; Lupori, Leonardo; Mazziotti, Raffaele; Medici, Giorgio; Lo Martire, Viviana; Ren, Elisa; Rimondini, Roberto; Zoccoli, Giovanna; Bartesaghi, Renata; Pizzorusso, Tommaso; Ciani, Elisabetta

2018-05-01

Cyclin-dependent kinase like-5 (CDKL5) disorder is a rare neurodevelopmental disease caused by mutations in the CDKL5 gene. The consequent misexpression of the CDKL5 protein in the nervous system leads to a severe phenotype characterized by intellectual disability, motor impairment, visual deficits and early-onset epilepsy. No therapy is available for CDKL5 disorder. It has been reported that a protein transduction domain (TAT) is able to deliver macromolecules into cells and even into the brain when fused to a given protein. We demonstrate that TAT-CDKL5 fusion protein is efficiently internalized by target cells and retains CDKL5 activity. Intracerebroventricular infusion of TAT-CDKL5 restored hippocampal development, hippocampus-dependent memory and breathing pattern in Cdkl5-null mice. Notably, systemically administered TAT-CDKL5 protein passed the blood-brain-barrier, reached the CNS, and rescued various neuroanatomical and behavioral defects, including breathing pattern and visual responses. Our results suggest that CDKL5 protein therapy may be an effective clinical tool for the treatment of CDKL5 disorder.

The impact of indicated prevention and early intervention on co-morbid eating disorder and depressive symptoms: a systematic review.

Science.gov (United States)

Rodgers, Rachel F; Paxton, Susan J

2014-01-01

Depressive and eating disorder symptoms are highly comorbid. To date, however, little is known regarding the efficacy of existing programs in decreasing concurrent eating disorder and depressive symptoms. We conducted a systematic review of selective and indicated controlled prevention and early intervention programs that assessed both eating disorder and depressive symptoms. We identified a total of 26 studies. The large majority of identified interventions (92%) were successful in decreasing eating disorder symptoms. However fewer than half (42%) were successful in decreasing both eating disorder and depressive symptoms. Intervention and participant characteristics did not predict success in decreasing depressive symptoms. Indicated prevention and early intervention programs targeting eating disorder symptoms are limited in their success in decreasing concurrent depressive symptoms. Further efforts to develop more efficient interventions that are successful in decreasing both eating disorder and depressive symptoms are warranted.

Early Detection of Autism Spectrum Disorder in Young isiZulu-Speaking Children in South Africa

Science.gov (United States)

Chambers, Nola J.; Wetherby, Amy M.; Stronach, Sheri T.; Njongwe, Nonyameko; Kauchali, Shuaib; Grinker, Richard R.

2017-01-01

Culturally appropriate tools are needed for detecting symptoms of autism spectrum disorder in young South African children. The objectives of this study were to (1) adapt and translate into isiZulu existing measures for detecting early signs of autism spectrum disorder, (2) use the measures to characterize and compare behavioural profiles of young…

Contribution of Schwann Cells to Remyelination in a Naturally Occurring Canine Model of CNS Neuroinflammation.

Directory of Open Access Journals (Sweden)

Kristel Kegler

Full Text Available Gliogenesis under pathophysiological conditions is of particular clinical relevance since it may provide evidence for regeneration promoting cells recruitable for therapeutic purposes. There is evidence that neurotrophin receptor p75 (p75NTR-expressing cells emerge in the lesioned CNS. However, the phenotype and identity of these cells, and signals triggering their in situ generation under normal conditions and certain pathological situations has remained enigmatic. In the present study, we used a spontaneous, idiopathic and inflammatory CNS condition in dogs with prominent lympho-histiocytic infiltration as a model to study the phenotype of Schwann cells and their relation to Schwann cell remyelination within the CNS. Furthermore, the phenotype of p75NTR-expressing cells within the injured CNS was compared to their counter-part in control sciatic nerve and after peripheral nerve injury. In addition, organotypic slice cultures were used to further elucidate the origin of p75NTR-positive cells. In cerebral and cerebellar white and grey matter lesions as well as in the brain stem, p75NTR-positive cells co-expressed the transcription factor Sox2, but not GAP-43, GFAP, Egr2/Krox20, periaxin and PDGFR-α. Interestingly, and contrary to the findings in control sciatic nerves, p75NTR-expressing cells only co-localized with Sox2 in degenerative neuropathy, thus suggesting that such cells might represent dedifferentiated Schwann cells both in the injured CNS and PNS. Moreover, effective Schwann cell remyelination represented by periaxin- and P0-positive mature myelinating Schwann cells, was strikingly associated with the presence of p75NTR/Sox2-expressing Schwann cells. Intriguingly, the emergence of dedifferentiated Schwann cells was not affected by astrocytes, and a macrophage-dominated inflammatory response provided an adequate environment for Schwann cells plasticity within the injured CNS. Furthermore, axonal damage was reduced in brain stem areas

The Use of Cannabis as a Predictor of Early Onset of Bipolar Disorder and Suicide Attempts

Directory of Open Access Journals (Sweden)

Rafaela Torres Portugal Leite

2015-01-01

Full Text Available Introduction. Bipolar disorder (BD implies risk of suicide. The age at onset (AAO of BD carries prognostic significance. Substance abuse may precede the onset of BD and cannabis is the most common illicit drug used. The main goal of this study is to review the association of cannabis use as a risk factor for early onset of BD and for suicide attempts. Materials and Methods. PubMed database was searched for articles using key words “bipolar disorder,” “suicide attempts,” “cannabis,” “marijuana,” “early age at onset,” and “early onset.” Results. The following percentages in bipolar patients were found: suicide attempts 3.6–42%; suicide attempts and substance use 5–60%; suicide attempts and cannabis use 15–42%. An early AAO was associated with cannabis misuse. The mean age of the first manic episode in individuals with and without BD and cannabis use disorder (CUD was 19.5 and 25.1 years, respectively. The first depressive episode was at 18.5 and 24.4 years, respectively. Individuals misusing cannabis showed increased risk of suicide. Discussion. Cannabis use is associated with increased risk of suicide attempts and with early AAO. However, the effect of cannabis at the AAO and suicide attempts is not clear.

Is ADHD an early stage in the development of borderline personality disorder?

DEFF Research Database (Denmark)

Storebø, Ole Jakob; Simonsen, Erik

2014-01-01

BACKGROUND: Several studies report associations between adults with borderline personality disorder (BPD) and a history of attention-deficit hyperactivity (ADHD) symptoms in childhood. AIMS: To explore the association between BPD and a history of ADHD in childhood. METHOD: A comprehensive search......: Most of the 15 articles showed a statistical association between ADHD and BPD. The data, most strongly provided a basis for the hypotheses that ADHD is either an early developmental stage of BPD, or that the two disorders share an environmental and genetic aetiology. Furthermore, one of the disorders...... seems to give a synergic effect, reinforce the other or complicate the disorders. In one prospective study, the risk factor for children with ADHD to develop BPD was as high as odds ratio 13.16. No studies have looked at treatment of ADHD as a mediator of the risk for BPD. CONCLUSIONS: Many studies...

Intellectual abilities among survivors of childhood leukaemia as a function of CNS irradiation

International Nuclear Information System (INIS)

Eiser, C.

1978-01-01

Twenty-eight children in remission at least 2 years after completing chemotherapy for acute lymphoblastic leukaemia were assessed on standardised psychological tests. It was found that 7 who never had central nervous system (CNS) irradiation and 9 having prophylactic CNS irradiation at least 6 months after diagnosis tended to perform at average or above levels, while those 10 each having prophylactic CNS irradiation (within 2 months of diagnosis) were generally at lower ability. Within the latter group 3 children showed serious intellectual impairments, while the group as a whole functioned especially poorly on quantitative tasks and those involving speeded performance with abstract material. General language ability was not affected. Practical and theoretical implications are discussed. (author)

Predictors of early dropout in treatment for gambling disorder: The role of personality disorders and clinical syndromes.

Science.gov (United States)

Maniaci, G; La Cascia, C; Picone, F; Lipari, A; Cannizzaro, C; La Barbera, D

2017-11-01

Several treatment options for gambling disorder (GD) have been tested in recent years; however dropout levels still remain high. This study aims to evaluate whether the presence of psychiatric comorbidities predicts treatment outcome according to Millon's evolutionary theory, following a six-month therapy for GD. The role of severity, duration of the disorder, typology of gambling (mainly online or offline) and pharmacological treatment were also analysed. The recruitment included 194 pathological gamblers (PGs) to be compared with 78 healthy controls (HCs). Psychological assessment included the South Oaks Gambling Screen and the Millon Clinical Multiaxial Inventory-III. The "treatment failure" group (n = 70) comprised PGs who prematurely dropped out of the treatment whereas the "abstinent group" (n = 124) included PGs who completed the treatment regardless of whether the outcome was successful or not. As expected, the presence of psychiatric comorbidities was highlighted as a significant predictor in dropping out of the therapy. Specifically negativistic personality disorder, antisocial personality disorder, drug dependence and PTSD were associated with early dropout. These variables were predictive of treatment outcome independently from the typology of gambling, severity, duration of the disorder and pharmacological treatment. Implications for psychological and psychiatric care are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy.

Science.gov (United States)

Fehr, Stephanie; Wilson, Meredith; Downs, Jenny; Williams, Simon; Murgia, Alessandra; Sartori, Stefano; Vecchi, Marilena; Ho, Gladys; Polli, Roberta; Psoni, Stavroula; Bao, Xinhua; de Klerk, Nick; Leonard, Helen; Christodoulou, John

2013-03-01

The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant.

Eating disorder symptom trajectories in adolescence: effects of time, participant sex, and early adolescent depressive symptoms.

Science.gov (United States)

Allen, Karina L; Crosby, Ross D; Oddy, Wendy H; Byrne, Susan M

2013-01-01

Adolescence is a period of developmental risk for eating disorders and eating disorder symptoms. This study aimed to describe the prevalence and trajectory of five core eating disorder behaviours (binge eating, purging, fasting, following strict dietary rules, and hard exercise for weight control) and a continuous index of dietary restraint and eating, weight and shape concerns, in a cohort of male and female adolescents followed from 14 to 20 years. It also aimed to determine the effect of early adolescent depressive symptoms on the prevalence and trajectory of these different eating disorder symptoms. Participants (N = 1,383; 49% male) were drawn from the Western Australian Pregnancy Cohort (Raine) Study, a prospective cohort study that has followed participants from pre-birth to age 20 years. An adapted version of the Eating Disorder Examination-Questionnaire was used to assess eating disorder symptoms at ages 14, 17 and 20 years. The Beck Depression Inventory for Youth was used to assess depressive symptoms at age 14. Longitudinal changes in the prevalence of eating disorder symptoms were tested using generalised estimating equations and linear mixed models. Symptom trajectories varied according to the eating disorder symptom studied, participant sex, and the presence of depressive symptoms in early adolescence. For males, eating disorder symptoms tended to be stable (for purging, fasting and hard exercise) or decreasing (for binge eating and global symptom scores) from 14 to 17 years, and then stable to 20 years. For females, fasting and global symptom scores increased from age 14 to peak in prevalence at age 17. Rates of binge eating in females were stable from age 14 to age 17 and increased significantly thereafter, whilst rates of purging and hard exercise increased from age 14 to age 17, and then remained elevated through to age 20. Depressive symptoms at age 14 impacted on eating disorder symptom trajectories in females, but not in males. Prevention

Developmental and Communication Disorders in Children with Intellectual Disability: The Place Early Intervention for Effective Inclusion

Science.gov (United States)

Jacob, Udeme Samuel; Olisaemeka, Angela Nneka; Edozie, Isioma Sitamalife

2015-01-01

The paper attempts to discuss the place of intervention in the developmental and communication disorders of children with intellectual disability for the purpose of providing effective inclusion programme. The definition of early intervention was stated, areas affected by children communication disorder such as language comprehension, fluency,…

Therapeutic Role and Drug Delivery Potential of Neuroinflammation as a Target in Neurodegenerative Disorders.

Science.gov (United States)

Singh, Abhijeet; Chokriwal, Ankit; Sharma, Madan Mohan; Jain, Devendra; Saxena, Juhi; Stephen, Bjorn John

2017-08-16

Neuroinflammation, the condition associated with the hyperactivity of immune cells within the CNS (central nervous system), has recently been linked to a host range of neurodegenerative disorders. Targeting neuroinflammation could be of prime importance as recent research highlights the beneficial aspects associated with modulating the inflammatory mediators associated with the CNS. One of the main obstructions in neuroinflammatory treatments is the hindrance posed by the blood-brain barrier for the delivery of drugs. Hence, research has focused on novel modes of transport for drugs to cross the barrier through drug delivery and nanotechnology approaches. In this Review, we highlight the therapeutic advancement made in the field of neurodegenerative disorders by focusing on the effect neuroinflammation treatment has on these conditions.

P-glycoprotein trafficking as a therapeutic target to optimize CNS drug delivery.

Science.gov (United States)

Davis, Thomas P; Sanchez-Covarubias, Lucy; Tome, Margaret E

2014-01-01

The primary function of the blood-brain barrier (BBB)/neurovascular unit is to protect the central nervous system (CNS) from potentially harmful xenobiotic substances and maintain CNS homeostasis. Restricted access to the CNS is maintained via a combination of tight junction proteins as well as a variety of efflux and influx transporters that limits the transcellular and paracellular movement of solutes. Of the transporters identified at the BBB, P-glycoprotein (P-gp) has emerged as the transporter that is the greatest obstacle to effective CNS drug delivery. In this chapter, we provide data to support intracellular protein trafficking of P-gp within cerebral capillary microvessels as a potential target for improved drug delivery. We show that pain-induced changes in P-gp trafficking are associated with changes in P-gp's association with caveolin-1, a key scaffolding/trafficking protein that colocalizes with P-gp at the luminal membrane of brain microvessels. Changes in colocalization with the phosphorylated and nonphosphorylated forms of caveolin-1, by pain, are accompanied by dynamic changes in the distribution, relocalization, and activation of P-gp "pools" between microvascular endothelial cell subcellular compartments. Since redox-sensitive processes may be involved in signaling disassembly of higher-order structures of P-gp, we feel that manipulating redox signaling, via specific protein targeting at the BBB, may protect disulfide bond integrity of P-gp reservoirs and control trafficking to the membrane surface, providing improved CNS drug delivery. The advantage of therapeutic drug "relocalization" of a protein is that the physiological impact can be modified, temporarily or long term, despite pathology-induced changes in gene transcription. © 2014 Elsevier Inc. All rights reserved.

Glypicans and FGFs in CNS Development and Function

NARCIS (Netherlands)

Galli, Antonella

2003-01-01

One of the most important events during central nervous system (CNS) development is the communication between cells. Cell-to-cell signaling implicates the interaction between a signaling molecules (or ligands) and their receptors. Ligand-receptor interaction is a tightly regulated process and is

Early Life Stress, Nicotinic Acetylcholine Receptors and Alcohol Use Disorders

Directory of Open Access Journals (Sweden)

Joan Y. Holgate

2015-06-01

Full Text Available Stress is a major driving force in alcohol use disorders (AUDs. It influences how much one consumes, craving intensity and whether an abstinent individual will return to harmful alcohol consumption. We are most vulnerable to the effects of stress during early development, and exposure to multiple traumatic early life events dramatically increases the risk for AUDs. However, not everyone exposed to early life stress will develop an AUD. The mechanisms determining whether an individual’s brain adapts and becomes resilient to the effects of stress or succumbs and is unable to cope with stress remain elusive. Emerging evidence suggests that neuroplastic changes in the nucleus accumbens (NAc following early life stress underlie the development of AUDs. This review discusses the impact of early life stress on NAc structure and function, how these changes affect cholinergic signaling within the mesolimbic reward pathway and the role nicotinic acetylcholine receptors (nAChRs play in this process. Understanding the neural pathways and mechanism determining stress resilience or susceptibility will improve our ability to identify individuals susceptible to developing AUDs, formulate cognitive interventions to prevent AUDs in susceptible individuals and to elucidate and enhance potential therapeutic targets, such as the nAChRs, for those struggling to overcome an AUD.

Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

Energy Technology Data Exchange (ETDEWEB)

Vuillemenot, Brian R., E-mail: bvuillemenot@bmrn.com [BioMarin Pharmaceutical Inc., Novato, CA (United States); Kennedy, Derek [BioMarin Pharmaceutical Inc., Novato, CA (United States); Reed, Randall P.; Boyd, Robert B. [Northern Biomedical Research, Inc., Muskegon, MI (United States); Butt, Mark T. [Tox Path Specialists, LLC, Hagerstown, MD (United States); Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O' Neill, Charles A. [BioMarin Pharmaceutical Inc., Novato, CA (United States)

2014-05-15

CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

International Nuclear Information System (INIS)

Vuillemenot, Brian R.; Kennedy, Derek; Reed, Randall P.; Boyd, Robert B.; Butt, Mark T.; Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O'Neill, Charles A.

2014-01-01

CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

Autologous Bone Marrow Stromal Cell Transplantation for Central Nervous System Disorders – Recent Progress and Perspective for Clinical Application

Directory of Open Access Journals (Sweden)

Kuroda S

2011-01-01

Full Text Available There is increasing evidence that the transplanted BMSC significantly promote functional recovery after CNS damage in the animal models of various kinds of CNS disorders, including cerebral infarct, traumatic brain injury and spinal cord injury. However, there are several shortages of information when considering clinical application of BMSC transplantation for patients with CNS disorders. In this review, therefore, we discuss what we should clarify to establish cell transplantation therapy as the scientifically proven entity in clinical situation and describe our recent works for this purpose. The BMSC have the ability to alter their gene expression profile and phenotype in response to the surrounding circumstances and to protect the neurons by producing some neurotrophic factors. They also promote neurite extension and rebuild the neural circuits in the injured CNS. The BMSC can be expanded in vitro using the animal serum-free medium. Pharmacological modulation may accelerate the in vitro proliferation of the BMSC. Using in vivo optical imaging technique, the transplanted BMSC can non-invasively be tracked in the living animals for at least 8 weeks after transplantation. It is urgent issues to develop clinical imaging technique to track the transplanted cells in the CNS and evaluate the therapeutic significance of BMSC transplantation in order to establish it as a definite therapeutic strategy in clinical situation in the future.

Psychic blindness or visual agnosia: early descriptions of a nervous disorder.

Science.gov (United States)

Baumann, Christian

2011-01-01

This article briefly reports on three early contributions to the understanding of visual agnosia as a syndrome sui generis. The authors of the respective papers worked in different fields such as physiology, ophthalmology, and neurology, and, although they were not in direct contact with each other, their results converged upon a consistent view of a nervous disorder that they called psychic blindness.

Tailored central nervous system-directed treatment strategy for isolated CNS recurrence of adult acute myeloid leukemia.

Science.gov (United States)

Zheng, Changcheng; Liu, Xin; Zhu, Weibo; Cai, Xiaoyan; Wu, Jingsheng; Sun, Zimin

2014-06-01

The aim of this report was to investigate the tailored treatment strategies for isolated central nervous system (CNS) recurrence in adult patients with acute myeloid leukemia (AML). Isolated CNS recurrence was documented in 34 patients: there were 18, 6, and 10 patients with meningeal involvement type (type A), cranial nerve palsy type (type B), and myeloid sarcoma type (type C), respectively. For patients with type A, intrathecal chemotherapy was the predominant strategy. For type B, systemic HD-Ara-C with four cycles was the main treatment. For type C, cranial irradiation or craniospinal irradiation was adopted and two cycles of HD-Ara-C were given after the irradiation. The 5-year cumulative incidence of CNS recurrence was 12.8%. There was a significantly higher WBC count (32.6∼60.8 × 10(9)/l) in patients at first diagnosis who developed CNS recurrence (all of the three types) compared with patients with no CNS recurrence (10.1 × 10(9)/l) (P = 0.005). We found that a significantly more patients with AML-M5 and 11q23 abnormalities developed CNS recurrence in type A (P adult AML, but further studies are needed to improve the long-term survival.

Human neural stem cells differentiate and promote locomotor recovery in an early chronic spinal cord injury NOD-scid mouse model.

Directory of Open Access Journals (Sweden)

Desirée L Salazar

2010-08-01

Full Text Available Traumatic spinal cord injury (SCI results in partial or complete paralysis and is characterized by a loss of neurons and oligodendrocytes, axonal injury, and demyelination/dysmyelination of spared axons. Approximately 1,250,000 individuals have chronic SCI in the U.S.; therefore treatment in the chronic stages is highly clinically relevant. Human neural stem cells (hCNS-SCns were prospectively isolated based on fluorescence-activated cell sorting for a CD133(+ and CD24(-/lo population from fetal brain, grown as neurospheres, and lineage restricted to generate neurons, oligodendrocytes and astrocytes. hCNS-SCns have recently been transplanted sub-acutely following spinal cord injury and found to promote improved locomotor recovery. We tested the ability of hCNS-SCns transplanted 30 days post SCI to survive, differentiate, migrate, and promote improved locomotor recovery.hCNS-SCns were transplanted into immunodeficient NOD-scid mice 30 days post spinal cord contusion injury. hCNS-SCns transplanted mice demonstrated significantly improved locomotor recovery compared to vehicle controls using open field locomotor testing and CatWalk gait analysis. Transplanted hCNS-SCns exhibited long-term engraftment, migration, limited proliferation, and differentiation predominantly to oligodendrocytes and neurons. Astrocytic differentiation was rare and mice did not exhibit mechanical allodynia. Furthermore, differentiated hCNS-SCns integrated with the host as demonstrated by co-localization of human cytoplasm with discrete staining for the paranodal marker contactin-associated protein.The results suggest that hCNS-SCns are capable of surviving, differentiating, and promoting improved locomotor recovery when transplanted into an early chronic injury microenvironment. These data suggest that hCNS-SCns transplantation has efficacy in an early chronic SCI setting and thus expands the "window of opportunity" for intervention.

Microparticles: A New Perspective in Central Nervous System Disorders

Directory of Open Access Journals (Sweden)

Stephanie M. Schindler

2014-01-01

Full Text Available Microparticles (MPs are a heterogeneous population of small cell-derived vesicles, ranging in size from 0.1 to 1 μm. They contain a variety of bioactive molecules, including proteins, biolipids, and nucleic acids, which can be transferred between cells without direct cell-to-cell contact. Consequently, MPs represent a novel form of intercellular communication, which could play a role in both physiological and pathological processes. Growing evidence indicates that circulating MPs contribute to the development of cancer, inflammation, and autoimmune and cardiovascular diseases. Most cell types of the central nervous system (CNS have also been shown to release MPs, which could be important for neurodevelopment, CNS maintenance, and pathologies. In disease, levels of certain MPs appear elevated; therefore, they may serve as biomarkers allowing for the development of new diagnostic tools for detecting the early stages of CNS pathologies. Quantification and characterization of MPs could also provide useful information for making decisions on treatment options and for monitoring success of therapies, particularly for such difficult-to-treat diseases as cerebral malaria, multiple sclerosis, and Alzheimer’s disease. Overall, studies on MPs in the CNS represent a novel area of research, which promises to expand the knowledge on the mechanisms governing some of the physiological and pathophysiological processes of the CNS.

Microparticles: A New Perspective in Central Nervous System Disorders

Science.gov (United States)

Schindler, Stephanie M.; Little, Jonathan P.

2014-01-01

Microparticles (MPs) are a heterogeneous population of small cell-derived vesicles, ranging in size from 0.1 to 1 μm. They contain a variety of bioactive molecules, including proteins, biolipids, and nucleic acids, which can be transferred between cells without direct cell-to-cell contact. Consequently, MPs represent a novel form of intercellular communication, which could play a role in both physiological and pathological processes. Growing evidence indicates that circulating MPs contribute to the development of cancer, inflammation, and autoimmune and cardiovascular diseases. Most cell types of the central nervous system (CNS) have also been shown to release MPs, which could be important for neurodevelopment, CNS maintenance, and pathologies. In disease, levels of certain MPs appear elevated; therefore, they may serve as biomarkers allowing for the development of new diagnostic tools for detecting the early stages of CNS pathologies. Quantification and characterization of MPs could also provide useful information for making decisions on treatment options and for monitoring success of therapies, particularly for such difficult-to-treat diseases as cerebral malaria, multiple sclerosis, and Alzheimer's disease. Overall, studies on MPs in the CNS represent a novel area of research, which promises to expand the knowledge on the mechanisms governing some of the physiological and pathophysiological processes of the CNS. PMID:24860829

[A review of the effects of lithium on cognitive functions: Effects on the neuropsychiatrically challenged CNS].

Science.gov (United States)

Tsaltas, E; Kontis, D

2009-04-01

Recent data attribute neuroprotective and neurotrophic actions to lithium, leading to expectations of cognitive enhancement action. This hypothesis is at odds with the predominant view of clinical psychiatr y which, on the basis of older clinical data as well as on subjective reports of lithiumtreated patients, associates lithium with cognitive blurring and specific memory deficits. Review of the older data and their integration with more recent clinical and experimental work on the primary effects of lithium on cognitive functioning led us to two central conclusions: (a) Data on the primary cognitive effects of lithium, considered in their entirety, do not support a picture of serious or long-lasting cognitive decline. On the contrary, recent evidence suggests cognitive enhancement under certain conditions. (b) The conditions which appear to promote the emergence of cognitive enhancement under lithium are conditions of challenge to the cognitive systems, such as increased task difficulty resulting in deterioration in the performance of untreated controls. We are suggesting that alternative challenges to cognitive functioning, which therefore would facilitate the emergence of lithium's cognitive enhancement action, include biological insults to the central nervous system (CNS). This second part of our review of the cognitive effects of lithium therefore focuses on studies of its action on cognitive dysfunction associated with functional or biological challenge to the CNS, such as stress, trauma, neurodegenerative and psychiatric disorders.

Treatment options for Primary CNS Lymphoma.

Science.gov (United States)

Laghari, Altaf Ali; Ahmed, Syed Ijlal; Jabbar, Adnan; Shamim, Muhammad Shahzad

2018-03-01

Primary CNS lymphoma (PCNSL) is a rare and aggressive brain tumour that is uniformly fatal. The rarity of the disease and the poor response to treatment makes it difficult to reach a consensus with regards to treatment options. In this review, the authors have discussed different treatment modalities used in the management of PCNSL including chemotherapy, surgery and radiation, as well as the results of recent clinical trials on treatment options for PCNSL.

Ketamine displaces the novel NMDA receptor SPET probe [{sup 123}I]CNS-1261 in humans in vivo

Energy Technology Data Exchange (ETDEWEB)

Stone, James M. [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom)]. E-mail: j.stone@iop.kcl.ac.uk; Erlandsson, Kjell [Institute of Nuclear Medicine, University College London, London, W1N 8AA (United Kingdom); Arstad, Erik [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom); Bressan, Rodrigo A. [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom); Squassante, Lisa [GlaxoSmithKline (GSK), Verona 37135 (Italy); Teneggi, Vincenza [GlaxoSmithKline (GSK), Verona 37135 (Italy); Ell, Peter J. [Institute of Nuclear Medicine, University College London, London, W1N 8AA (United Kingdom); Pilowsky, Lyn S. [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom); Institute of Nuclear Medicine, University College London, London, W1N 8AA (United Kingdom)

2006-02-15

[{sup 123}I]CNS-1261 [N-(1-naphthyl)-N'-(3-iodophenyl)-N-methylguanidine] is a high-affinity SPET ligand with selectivity for the intrachannel PCP/ketamine/MK-801 site of the N-methyl-D-aspartate (NMDA) receptor. This study evaluated the effects of ketamine (a specific competitor for the intrachannel PCP/ketamine/MK-801 site) on [{sup 123}I]CNS-1261 binding to NMDA receptors in vivo. Ten healthy volunteers underwent 2 bolus-plus-infusion [{sup 123}I]CNS-1261 scans, one during placebo and the other during a ketamine challenge. Ketamine administration led to a significant decrease in [{sup 123}I]CNS-1261 V {sub T} in most of the brain regions examined (P<.05). [{sup 123}I]CNS-1261 appears to be a specific ligand in vivo for the intrachannel PCP/ketamine/MK-801 NMDA binding site.

Nuclear innovation through collaboration. 35th Annual CNS conference and 39th CNS/CNA student conference

Energy Technology Data Exchange (ETDEWEB)

NONE

2015-07-01

The Canadian Nuclear Society (CNS) held its 35th Annual Conference in Saint John, New Brunswick, Canada on May 31 to June 3, 2015, combined with the 39th Annual CNS/CNA Student Conference. With the theme of the conference, 'Nuclear Innovation through Collaboration', more than 425 delegates, exhibitors and students were in attendance. The conference commenced with two strong plenary sessions on Utility Collaborations to Improve Lifetime Performance; and, Performance Improvement Programs: Goals and Experience. The second day consisted of the panel discussions on International Developments in Used Nuclear Fuel Repository Programs, and two plenary sessions on: Enterprise Risk Management; and, Vendor Role in a Continuously Improving Industry. The third day contained a number of interesting features, including plenary sessions on Waste Management and Decommissioning; Developing Technologies and Resources, and a panel discussion on the Transportation of Used Nuclear Fuel. All three days of the conference also contained parallel sessions with over 100 technical papers presented at the main and student sessions. The technical session titles were: Refurbishment and Life Extension; Thermalhydraulics; Nuclear Materials; WMD - Radiation Monitoring; Safety and Licensing; Communication; Safety and Licensing; Instrumentation and Control; Advanced Reactor Designs; WMD - Deep Geological Repository Packaging; Reactor Physics; Chemistry and Materials; Advanced Fuel Cycles; Waste Management and Decommissioning; and, Medical Physics and Radiation Biology.

Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson's disease.

Science.gov (United States)

Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C; Mackay, Clare E; Hu, Michele T M

2016-08-01

SEE POSTUMA DOI101093/AWW131 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson's disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson's disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson's disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson's disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson's disease and 10 control subjects received (123)I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye movement sleep

Early childhood experiences shaping vulnerability to Obsessive-Compulsive Disorder

Directory of Open Access Journals (Sweden)

Barbara Barcaccia

2015-12-01

Full Text Available According to the literature, inflated responsibility/sensitivity to guilt play a pivotal role in both the genesis and maintenance of Obsessive-Compulsive Disorder (OCD. They may be learned in childhood and adolescence, through particular experiences and parental rearing styles, involving criticism, excessively high standards, and social moralization. Preliminary data on the role of dysfunctional beliefs in the development/maintenance of OCD also show that non-affected family members of OC individuals score higher than controls in domains concerning responsibility, suggesting it might represent a candidate endophenotype for the disorder. Compulsive conducts, that far from being mechanical reactions are instead clearly goal-oriented, may be triggered by the need of preventing responsibility/guilt. Therefore, useful psychological interventions aimed at not only reappraising meanings associated with the specific early experiences connected to hyper-sensitivity to guilt, but also at developing a more general compassionate and forgiving stance towards oneself, may prove particularly effective.

Results from a pediatric surgical centre justify early intervention in disorders of sex development.

Science.gov (United States)

Crawford, Jennifer M; Warne, Garry; Grover, Sonia; Southwell, Bridget R; Hutson, John M

2009-02-01

Controversy persists surrounding early management of disorders of sex development. We assessed genital appearance, gender identity, and quality of life in prepubertal children who have had early surgical intervention. Children treated for disorders of sex development who were 5 to 10 years of age were eligible (n = 54). Children were scored (modified Creighton scale) for anatomical and cosmetic outcome, and both patients and parents completed PedsQL quality-of-life and gender identity questionnaires, with ethics approval. Of 54 patients, 41 presented for review. Treatment began at 13.2 (1.8-250.1) months (median; range) and were reviewed at 7.5 +/- 2.1 (mean +/- SD) years of age. Nineteen were raised as girls and 22 as boys. Girls had good (85%) or satisfactory (15%) anatomical/cosmetic outcome, whereas 52% boys had good, 38% satisfactory, and 10% poor cosmetic outcomes. On gender identity questionnaire, boys scored 3.9 +/- 0.4 (mean +/- SD) and girls 3.6 +/- 0.5; 1 of 19 boys and 3 of 19 girls had lower scores, suggesting risk of gender identity disorder. Quality-of-life scores were 80+ for physical and 65 to 80 for psychosocial scores. Early intervention is generally associated with positive outcomes for patients and parents. Girls had better anatomical outcomes than boys, and gender dysphoria risks were low in both sexes.

Behavioural and skill-based early interventions in children with autism spectrum disorders

Directory of Open Access Journals (Sweden)

Greiner, Wolfgang

2009-07-01

Full Text Available Introduction: Autism spectrum disorders (ASD comprise typical or infantile autism (Kanner syndrome, Asperger’s disorder and atypical autism or pervasive developmental disorder - not otherwise specified. The syndrome is characterized by deficits in (1 verbal and nonverbal communication, (2 reciprocal social interaction and (3 repetitive patterns of behaviour, interests and activities. Early behavioural interventions are based on learning theory and behaviour therapy. They take into account specific deficits in perception, emotional reactions, social interaction and communication. In Germany, these comprehensive models are not widely evaluated and implemented. Research questions: * What are the clinical effectiveness and safety of early behavioural or skills-based early interventions in autism compared to other interventions or to treatment as usual? * What are specific factors responsible for the effectiveness? * What are the cost-effectiveness and cost consequences of different early interventions in autism? * Which legal, social and ethical aspects are relevant with regard to the implementation of the respective interventions in persons with autism? Methods: Following a systematic review of the literature, controlled studies on early behavioural or skills-based interventions published since 2000 in English or German with children until the age of twelve are included and critically appraised. Studies must have at least ten participants per intervention group. Results: In total, 15 publications based on 14 studies, eight systematic reviews and one health economic study are included. Most studies evaluate early interventions based upon the Lovaas model (Early intensive behavioural treatment (EIBT, Applied behavioural analysis (ABA. Other evaluate pragmatic interventions or interventions based on other theoretical models like specific parent interventions, responsive education and prelinguistic milieu teaching, joint attention, symbolic play, and

Behavioural and skill-based early interventions in children with autism spectrum disorders.

Science.gov (United States)

Weinmann, Stefan; Schwarzbach, Christoph; Begemann, Matthias; Roll, Stephanie; Vauth, Christoph; Willich, Stefan N; Greiner, Wolfgang

2009-07-29

Autism spectrum disorders (ASD) comprise typical or infantile autism (Kanner syndrome), Asperger's disorder and atypical autism or pervasive developmental disorder - not otherwise specified. The syndrome is characterized by deficits in (1) verbal and nonverbal communication, (2) reciprocal social interaction and (3) repetitive patterns of behaviour, interests and activities. Early behavioural interventions are based on learning theory and behaviour therapy. They take into account specific deficits in perception, emotional reactions, social interaction and communication. In Germany, these comprehensive models are not widely evaluated and implemented. What are the clinical effectiveness and safety of early behavioural or skills-based early interventions in autism compared to other interventions or to treatment as usual?What are specific factors responsible for the effectiveness?What are the cost-effectiveness and cost consequences of different early interventions in autism?Which legal, social and ethical aspects are relevant with regard to the implementation of the respective interventions in persons with autism? Following a systematic review of the literature, controlled studies on early behavioural or skills-based interventions published since 2000 in English or German with children until the age of twelve are included and critically appraised. Studies must have at least ten participants per intervention group. In total, 15 publications based on 14 studies, eight systematic reviews and one health economic study are included. Most studies evaluate early interventions based upon the Lovaas model (Early intensive behavioural treatment (EIBT), Applied behavioural analysis (ABA)). Other evaluate pragmatic interventions or interventions based on other theoretical models like specific parent interventions, responsive education and prelinguistic milieu teaching, joint attention, symbolic play, and picture exchange communication system. Behaviour analytic interventions

Behavioural and skill-based early interventions in children with autism spectrum disorders

Science.gov (United States)

Weinmann, Stefan; Schwarzbach, Christoph; Begemann, Matthias; Roll, Stephanie; Vauth, Christoph; Willich, Stefan N.; Greiner, Wolfgang

2009-01-01

Introduction Autism spectrum disorders (ASD) comprise typical or infantile autism (Kanner syndrome), Asperger’s disorder and atypical autism or pervasive developmental disorder - not otherwise specified. The syndrome is characterized by deficits in (1) verbal and nonverbal communication, (2) reciprocal social interaction and (3) repetitive patterns of behaviour, interests and activities. Early behavioural interventions are based on learning theory and behaviour therapy. They take into account specific deficits in perception, emotional reactions, social interaction and communication. In Germany, these comprehensive models are not widely evaluated and implemented. Research questions What are the clinical effectiveness and safety of early behavioural or skills-based early interventions in autism compared to other interventions or to treatment as usual? What are specific factors responsible for the effectiveness? What are the cost-effectiveness and cost consequences of different early interventions in autism? Which legal, social and ethical aspects are relevant with regard to the implementation of the respective interventions in persons with autism? Methods Following a systematic review of the literature, controlled studies on early behavioural or skills-based interventions published since 2000 in English or German with children until the age of twelve are included and critically appraised. Studies must have at least ten participants per intervention group. Results In total, 15 publications based on 14 studies, eight systematic reviews and one health economic study are included. Most studies evaluate early interventions based upon the Lovaas model (Early intensive behavioural treatment (EIBT), Applied behavioural analysis (ABA)). Other evaluate pragmatic interventions or interventions based on other theoretical models like specific parent interventions, responsive education and prelinguistic milieu teaching, joint attention, symbolic play, and picture exchange

Neurocognition in early-onset schizophrenia and schizoaffective disorders.

Science.gov (United States)

Hooper, Stephen R; Giuliano, Anthony J; Youngstrom, Eric A; Breiger, David; Sikich, Linmarie; Frazier, Jean A; Findling, Robert L; McClellan, Jon; Hamer, Robert M; Vitiello, Benedetto; Lieberman, Jeffrey A

2010-01-01

We examined the neuropsychological functioning of youth enrolled in the NIMH funded trial, Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). We compared the baseline neuropsychological functioning of youth with schizophrenia (SZ, n = 79) to those with schizoaffective disorder (SA, n = 40), and examined the relationship of different variables of illness severity and adaptive behavior to neuropsychological functioning. Participants ranged in age from 8 to 19 years. Diagnostic status was confirmed via structured interview over multiple time points. Domains of neuropsychological functioning included fine-motor, attention, working memory, problem-solving efficiency, inhibitory control, and social cognition. Other variables included intelligence (IQ), academic achievement skills, adaptive behavior, and different measures of illness severity. The two groups did not differ on IQ or on any of the neuropsychological domains. The SZ group performed significantly lower in spelling. A high proportion of individuals in both groups reflected significant intellectual and academic achievement skill deficits. Significant correlations were found between the neurocognitive domains and both illness severity and adaptive behavior variables. There were few differences between the SZ and SA groups on IQ, achievement, or neuropsychological functioning; however, both groups showed significantly high rates of deficits in IQ and basic academic skills. Correlations of the neurocognitive functions with illness severity and adaptive behavior were small to moderate in magnitude. These findings continue to implicate the importance of neurocognitive functioning as a key area of vulnerability in the study of youth with schizophrenia spectrum disorders.

PRIMARY PREVENTION OF DIABETES MELLITUS: CORRECTION OF EARLY DISORDERS OF GLUCOSE METABOLISM IN CARDIOLOGY PRACTICE

Directory of Open Access Journals (Sweden)

M. N. Mamedov

2015-12-01

Full Text Available Early glucose metabolism disorders (GMD are of interest in development of effective approaches to prevention of type 2 diabetes mellitus (DM. Data of international clinical trials shows that early GMD are an independent risk factor for cardiovascular disease. The possibilities of GMD prevention and early treatment are discussed. Antihyperglycemic medications classification, their mode of action and efficacy are presented from evidence-based medicine point of view. This data confirms that successful DM primary prevention at early stage of GMD reduces the risk of cardiovascular complications.

Neonatal CNS infection and inflammation caused by Ureaplasma species: rare or relevant?

Science.gov (United States)

Glaser, Kirsten; Speer, Christian P

2015-02-01

Colonization with Ureaplasma species has been associated with adverse pregnancy outcome, and perinatal transmission has been implicated in the development of bronchopulmonary dysplasia in preterm neonates. Little is known about Ureaplasma-mediated infection and inflammation of the CNS in neonates. Controversy remains concerning its incidence and implication in the pathogenesis of neonatal brain injury. In vivo and in vitro data are limited. Despite improving care options for extremely immature preterm infants, relevant complications remain. Systematic knowledge of ureaplasmal infection may be of great benefit. This review aims to summarize pathogenic mechanisms, clinical data and diagnostic pitfalls. Studies in preterm and term neonates are critically discussed with regard to their limitations. Clinical questions concerning therapy or prophylaxis are posed. We conclude that ureaplasmas may be true pathogens, especially in preterm neonates, and may cause CNS inflammation in a complex interplay of host susceptibility, serovar pathogenicity and gestational age-dependent CNS vulnerability.

Serum neuropeptide Y in accident survivors with depression or posttraumatic stress disorder.

Science.gov (United States)

Nishi, Daisuke; Hashimoto, Kenji; Noguchi, Hiroko; Matsuoka, Yutaka

2014-06-01

Although neuropeptide Y (NPY) has received attention for its potential anti-depressive and anti-anxiety effect, evidence in humans has been limited. This study aimed to clarify the relationships between serum NPY and depressive disorders, and posttraumatic stress disorder (PTSD) in accident survivors. Depressive disorders and PTSD were diagnosed by structural interviews at 1-month follow-up, and serum NPY was measured at the first assessment and 1-month follow-up. Analysis of variance was used to investigate significance of the differences identified. Furthermore, resilience was measured by self-report questionnaires. Multiple linear regression analyses were used to examine the relationship between resilience and serum NPY. Three hundred accident survivors participated in the assessment at the first assessment, and 138 completed the assessment at 1-month follow-up. Twenty-six participants had major depressive disorder and 6 had minor depressive disorder. Nine participants had PTSD and 16 had partial PTSD. No relationship existed between serum NPY and depressive disorders, PTSD, and resilience. The results of cannot be compared with those of NPY in the central nervous system (CNS), but these findings might be due to the nature of depression and PTSD in accident survivors. Further studies are needed to examine the relationships between NPY in CNS and depression and PTSD. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

CNS autoimmune disease after Streptococcus pyogenes infections: animal models, cellular mechanisms and genetic factors

Science.gov (United States)

Cutforth, Tyler; DeMille, Mellissa MC; Agalliu, Ilir; Agalliu, Dritan

2016-01-01

Streptococcus pyogenes infections have been associated with two autoimmune diseases of the CNS: Sydenham’s chorea (SC) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections (PANDAS). Despite the high frequency of pharyngeal streptococcus infections among children, only a small fraction develops SC or PANDAS. This suggests that several factors in combination are necessary to trigger autoimmune complications: specific S. pyogenes strains that induce a strong immune response toward the host nervous system; genetic susceptibility that predispose children toward an autoimmune response involving movement or tic symptoms; and multiple infections of the throat or tonsils that lead to a robust Th17 cellular and humoral immune response when untreated. In this review, we summarize the evidence for each factor and propose that all must be met for the requisite neurovascular pathology and behavioral deficits found in SC/PANDAS. PMID:27110222

Chemokines in the balance: maintenance of homeostasis and protection at CNS barriers

Directory of Open Access Journals (Sweden)

Jessica L Williams

2014-05-01

Full Text Available In the adult central nervous system (CNS, chemokines and their receptors are involved in developmental, physiological and pathological processes. Although most lines of investigation focus on their ability to induce the migration of cells, recent studies indicate that chemokines also promote cellular interactions and activate signaling pathways that maintain CNS homeostatic functions. Many homeostatic chemokines are expressed on the vasculature of the blood brain barrier including CXCL12, CCL19, CCL20, and CCL21. While endothelial cell expression of these chemokines is known to regulate the entry of leukocytes into the CNS during immunosurveillance, new data indicate that CXCL12 is also involved in diverse cellular activities including adult neurogenesis and neuronal survival, having an opposing role to the homeostatic chemokine, CXCL14, which appears to regulate synaptic inputs to neural precursors. Neuronal expression of CX3CL1, yet another homeostatic chemokine that promotes neuronal survival and communication with microglia, is partly regulated by CXCL12. Regulation of CXCL12 is unique in that it may regulate its own expression levels via binding to its scavenger receptor CXCR7/ACKR3. In this review, we explore the diverse roles of these and other homeostatic chemokines expressed within the CNS, including the possible implications of their dysfunction as a cause of neurologic disease.

Melatonin in Pregnancy: Effects on Brain Development and CNS Programming Disorders.

Science.gov (United States)

Sagrillo-Fagundes, Lucas; Assunção Salustiano, Eugênia Maria; Yen, Philippe Wong; Soliman, Ahmed; Vaillancourt, Cathy

2016-01-01

Melatonin is an important neuroprotective factor and its receptors are expressed in the fetal brain. During normal pregnancy, maternal melatonin level increases progressively until term and is highly transferred to the fetus, with an important role in brain formation and differentiation. Maternal melatonin provides the first circadian signal to the fetus. This indolamine is also produced de novo and plays a protective role in the human placenta. In pregnancy disorders, both maternal and placental melatonin levels are decreased. Alteration in maternal melatonin level has been associated with disrupted brain programming with long-term effects. Melatonin has strong antioxidant protective effects directly and indirectly via the activation of its receptors. The fetal brain is highly susceptible to oxygenation variation and oxidative stress that can lead to neuronal development disruption. Based on that, several approaches have been tested as a treatment in case of pregnancy disorders and melatonin, through its neuroprotective effect, has been recently accepted against fetal brain injury. This review provides an overview about the protective effects of melatonin during pregnancy and on fetal brain development.

Neuropsychological dysfunction in adults with early-onset obsessive-compulsive disorder: the search for a cognitive endophenotype

Directory of Open Access Journals (Sweden)

Jie Zhang

2015-06-01

Full Text Available Objective:Evidence suggests that early-onset obsessive-compulsive disorder (OCD is an etiologically distinct subtype of OCD. The objective of the present work was to search for neurocognitive endophenotypes of early-onset OCD based on assessments of attention, memory, and executive function in patients with the disorder and their unaffected siblings.Methods:We compared the performance of 40 adult patients with early-onset OCD, 40 of their unaffected siblings, and 40 unrelated healthy controls on a neuropsychological battery designed for this study. We searched for associations among test performance, demographic variables (age, sex and years of education and clinical symptoms of early-onset OCD.Results:Patients performed significantly worse than healthy controls on the Tower of Hanoi, and the Stroop and Wisconsin tests, indicating impairments in planning, mental flexibility and inhibitory control. The performance of the unaffected first-degree siblings of patients with early-onset OCD on the Stroop and Wisconsin tests also differed from that of healthy controls. Symptom severity in early-onset OCD was strongly correlated with performance on the Tower of Hanoi.Conclusions:Our findings support the existence of specific executive function deficits in patients with early-onset OCD. Relatives presented an intermediate phenotype between patients and controls, suggesting that executive functions such as mental flexibility and response inhibition may be considered candidate endophenotypes of early-onset OCD.

Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization-case study.

Science.gov (United States)

de Almeida, Sergio M; Rotta, Indianara; Ribeiro, Clea E; Oliveira, Michelli F; Chaillon, Antoine; de Pereira, Ana Paula; Cunha, Ana Paula; Zonta, Marise; Bents, Joao França; Raboni, Sonia M; Smith, Davey; Letendre, Scott; Ellis, Ronald J

2017-06-01

Despite the effective suppression of viremia with antiretroviral therapy, HIV can still replicate in the central nervous system (CNS). This was a longitudinal study of the cerebrospinal fluid (CSF) and serum dynamics of several biomarkers related to inflammation, the blood-brain barrier, neuronal injury, and IgG intrathecal synthesis in serial samples of CSF and serum from a patient infected with HIV-1 subtype C with CNS compartmentalization.The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation sequencing and F-statistics analysis of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples. The CSF biomarker analysis in this patient showed that symptomatic CSF escape is accompanied by CNS inflammation, high levels of cell and humoral immune biomarkers, CNS barrier dysfunction, and an increase in neuronal injury biomarkers with demyelization. Independent and isolated HIV replication can occur in the CNS, even in HIV-1 subtype C, leading to compartmentalization and development of quasispecies distinct from the peripheral plasma. These immunological aspects of the HIV CNS escape have not been described previously. To our knowledge, this is the first report of CNS HIV escape and compartmentalization in HIV-1 subtype C.

Clearance of an immunosuppressive virus from the CNS coincides with immune reanimation and diversification

Directory of Open Access Journals (Sweden)

McGavern Dorian B

2007-06-01

Full Text Available Abstract Once a virus infection establishes persistence in the central nervous system (CNS, it is especially difficult to eliminate from this specialized compartment. Therefore, it is of the utmost importance to fully understand scenarios during which a persisting virus is ultimately purged from the CNS by the adaptive immune system. Such a scenario can be found following infection of adult mice with an immunosuppressive variant of lymphocytic choriomeningitis virus (LCMV referred to as clone 13. In this study we demonstrate that following intravenous inoculation, clone 13 rapidly infected peripheral tissues within one week, but more slowly inundated the entire brain parenchyma over the course of a month. During the establishment of persistence, we observed that genetically tagged LCMV-specific cytotoxic T lymphocytes (CTL progressively lost function; however, the severity of this loss in the CNS was never as substantial as that observed in the periphery. One of the most impressive features of this model system is that the peripheral T cell response eventually regains functionality at ~60–80 days post-infection, and this was associated with a rapid decline in virus from the periphery. Coincident with this "reanimation phase" was a massive influx of CD4 T and B cells into the CNS and a dramatic reduction in viral distribution. In fact, olfactory bulb neurons served as the last refuge for the persisting virus, which was ultimately purged from the CNS within 200 days post-infection. These data indicate that a functionally revived immune response can prevail over a virus that establishes widespread presence both in the periphery and brain parenchyma, and that therapeutic enhancement of an existing response could serve as an effective means to thwart long term CNS persistence.

Psychiatric comorbidities of adults with early- and late-onset attention-deficit/hyperactivity disorder.

Science.gov (United States)

Lin, Yu-Ju; Yang, Li-Kuang; Gau, Susan Shur-Fen

2016-06-01

We evaluated the psychiatric comorbidities in adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder as a function of recalled symptom onset before and after the age of 7 years and whether the childhood attention-deficit/hyperactivity disorder symptoms were associated with psychiatric comorbidities. In all, 214 adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder and 174 non-attention-deficit/hyperactivity disorder controls (aged 17-40 years) received psychiatric interviews to confirm their previous and current attention-deficit/hyperactivity disorder status and other psychiatric diagnoses. Demographics and risks of lifetime psychiatric disorders were compared among three groups: (1) attention-deficit/hyperactivity disorder, onset attention-deficit/hyperactivity disorder, onset between 7 and 12 years (late-onset) and (3) non-attention-deficit/hyperactivity disorder controls. We also tested the effects of attention-deficit/hyperactivity disorder symptoms on the risk of later psychiatric comorbidities by Cox regression analyses. Regardless of the age of onset, attention-deficit/hyperactivity disorder was significantly associated with a wide range of psychiatric comorbidities. There were similar comorbid patterns between early- and late-onset attention-deficit/hyperactivity disorder. Regardless of attention-deficit/hyperactivity disorder diagnosis, increased severity of attention-deficit/hyperactivity disorder symptoms was associated with higher risks of oppositional defiant disorder, conduct disorder, dysthymia and sleep disorder but not major depression, which was associated with the attention-deficit/hyperactivity disorder diagnosis. Our findings suggest that elevating the threshold of age of onset to 12 years in Diagnostic and Statistical Manual of Mental disorders, 5th edition would not

Imaging aspects of neurologic emergencies in children treated for non-CNS malignancies

International Nuclear Information System (INIS)

Kaste, S.C.; Langston, J.; Rodriguez-Galindo, C.; Furman, W.L.; Thompson, S.J.

2000-01-01

There is a paucity of radiologic literature addressing neurologic emergencies in children receiving therapy for non-CNS primary malignancies. In the acute setting, many of these children present to local community hospitals. This pictorial is from a single institutional experience describing the spectrum of neurologic emergencies seen in children with non-CNS cancers. We hope to familiarize pediatric radiologists with these entities in order to expedite diagnosis, facilitate treatment, and minimize morbity and mortality that may be associated with these complications. (orig.)

The Extracellular Environment of the CNS: Influence on Plasticity, Sprouting, and Axonal Regeneration after Spinal Cord Injury

Science.gov (United States)

Forbes, Lindsey H.

2018-01-01

The extracellular environment of the central nervous system (CNS) becomes highly structured and organized as the nervous system matures. The extracellular space of the CNS along with its subdomains plays a crucial role in the function and stability of the CNS. In this review, we have focused on two components of the neuronal extracellular environment, which are important in regulating CNS plasticity including the extracellular matrix (ECM) and myelin. The ECM consists of chondroitin sulfate proteoglycans (CSPGs) and tenascins, which are organized into unique structures called perineuronal nets (PNNs). PNNs associate with the neuronal cell body and proximal dendrites of predominantly parvalbumin-positive interneurons, forming a robust lattice-like structure. These developmentally regulated structures are maintained in the adult CNS and enhance synaptic stability. After injury, however, CSPGs and tenascins contribute to the structure of the inhibitory glial scar, which actively prevents axonal regeneration. Myelin sheaths and mature adult oligodendrocytes, despite their important role in signal conduction in mature CNS axons, contribute to the inhibitory environment existing after injury. As such, unlike the peripheral nervous system, the CNS is unable to revert to a “developmental state” to aid neuronal repair. Modulation of these external factors, however, has been shown to promote growth, regeneration, and functional plasticity after injury. This review will highlight some of the factors that contribute to or prevent plasticity, sprouting, and axonal regeneration after spinal cord injury. PMID:29849554

Tumor necrosis factor-alpha expression in peripheral blood mononuclear cells correlates with early childhood social interaction in autism spectrum disorder.

Science.gov (United States)

Makinodan, Manabu; Iwata, Keiko; Ikawa, Daisuke; Yamashita, Yasunori; Yamamuro, Kazuhiko; Toritsuka, Michihiro; Kimoto, Sohei; Okumura, Kazuki; Yamauchi, Takahira; Yoshino, Hiroki; Tsujii, Masatsugu; Sugiyama, Toshiro; Tsuchiya, Kenji; Mori, Norio; Matsuzaki, Hideo; Kishimoto, Toshifumi

2017-03-01

Autism spectrum disorder is a neurodevelopmental disorder characterized by impaired social interaction, poor communication skills, and repetitive/restrictive behaviors. Elevated blood levels of pro-inflammatory cytokines have been reported in subjects with autism spectrum disorder. On the other hand, early childhood adverse experience also increases blood levels of these cytokines. Since social experience of children with autism spectrum disorder is generally unlike to typically developing children, we hypothesized that social interaction during childhood contribute to pro-inflammatory cytokine expression in subjects with autism spectrum disorder. We compared revised Autism Diagnostic Interview scores and expression levels of pro-inflammatory cytokines in peripheral blood mononuclear cells of subjects with autism spectrum disorder (n = 30). The score of domain A on the revised Autism Diagnostic Interview, indicating social interaction impairment in early childhood, was negatively correlated with tumor necrosis factor-α mRNA expression level in peripheral blood mononuclear cells but not interleukin-1β or -6. Consistently, tumor necrosis factor-α mRNA expression was markedly low in subjects with autism spectrum disorder compared to typically developing children who presumably experienced the regular levels of social interaction. These findings suggest that the low blood levels of tumor necrosis factor-α mRNA in subjects with autism spectrum disorder might be due to impaired social interaction in early childhood. Copyright © 2016 Elsevier Ltd. All rights reserved.

Metallothionein-1+2 protect the CNS after a focal brain injury

DEFF Research Database (Denmark)

Giralt, Mercedes; Penkowa, Milena; Lago, Natalia

2002-01-01

We have evaluated the physiological relevance of metallothionein-1+2 (MT-1+2) in the CNS following damage caused by a focal cryolesion onto the cortex. In comparison to normal mice, transgenic mice overexpressing the MT-1 isoform (TgMTI* mice) showed a significant decrease of the number...... dramatically reduced the cryolesion-induced oxidative stress and neuronal apoptosis. Remarkably, these effects were also obtained by the intraperitoneal administration of MT-2 to both normal and MT-1+2 knock-out mice. These results fully support the notion that MT-1+2 are essential in the CNS for coping...

CNS recruitment of CD8+ T lymphocytes specific for a peripheral virus infection triggers neuropathogenesis during polymicrobial challenge.

Directory of Open Access Journals (Sweden)

Christine M Matullo

2011-12-01

Full Text Available Although viruses have been implicated in central nervous system (CNS diseases of unknown etiology, including multiple sclerosis and amyotrophic lateral sclerosis, the reproducible identification of viral triggers in such diseases has been largely unsuccessful. Here, we explore the hypothesis that viruses need not replicate in the tissue in which they cause disease; specifically, that a peripheral infection might trigger CNS pathology. To test this idea, we utilized a transgenic mouse model in which we found that immune cells responding to a peripheral infection are recruited to the CNS, where they trigger neurological damage. In this model, mice are infected with both CNS-restricted measles virus (MV and peripherally restricted lymphocytic choriomeningitis virus (LCMV. While infection with either virus alone resulted in no illness, infection with both viruses caused disease in all mice, with ∼50% dying following seizures. Co-infection resulted in a 12-fold increase in the number of CD8+ T cells in the brain as compared to MV infection alone. Tetramer analysis revealed that a substantial proportion (>35% of these infiltrating CD8+ lymphocytes were LCMV-specific, despite no detectable LCMV in CNS tissues. Mechanistically, CNS disease was due to edema, induced in a CD8-dependent but perforin-independent manner, and brain herniation, similar to that observed in mice challenged intracerebrally with LCMV. These results indicate that T cell trafficking can be influenced by other ongoing immune challenges, and that CD8+ T cell recruitment to the brain can trigger CNS disease in the apparent absence of cognate antigen. By extrapolation, human CNS diseases of unknown etiology need not be associated with infection with any particular agent; rather, a condition that compromises and activates the blood-brain barrier and adjacent brain parenchyma can render the CNS susceptible to pathogen-independent immune attack.

Clinical Spectrum, Etiology, and Outcome of Neurological Disorders in the Rural Hospital of Mosango, the Democratic Republic of Congo.

Science.gov (United States)

Mukendi, Deby; Lilo Kalo, Jean-Roger; Mpanya, Alain; Minikulu, Luigi; Kayembe, Tharcisse; Lutumba, Pascal; Barbé, Barbara; Gillet, Philippe; Jacobs, Jan; Van Loen, Harry; Yansouni, Cédric P; Chappuis, François; Ravinetto, Raffaella; Verdonck, Kristien; Boelaert, Marleen; Winkler, Andrea S; Bottieau, Emmanuel

2017-11-01

There is little published information on the epidemiology of neurological disorders in rural Central Africa, although the burden is considered to be substantial. This study aimed to investigate the pattern, etiology, and outcome of neurological disorders in children > 5 years and adults admitted to the rural hospital of Mosango, province of Kwilu, Democratic Republic of Congo, with a focus on severe and treatable infections of the central nervous system (CNS). From September 2012 to January 2015, 351 consecutive patients hospitalized for recent and/or ongoing neurological disorder were prospectively evaluated by a neurologist, subjected to a set of reference diagnostic tests in blood or cerebrospinal fluid, and followed-up for 3-6 months after discharge. No neuroimaging was available. Severe headache (199, 56.7%), gait/walking disorders (97, 27.6%), epileptic seizure (87, 24.8%), and focal neurological deficit (86, 24.5%) were the predominant presentations, often in combination. Infections of the CNS were documented in 63 (17.9%) patients and mainly included bacterial meningitis and unspecified meningoencephalitis (33, 9.4%), second-stage human African trypanosomiasis (10, 2.8%), and human immunodeficiency virus (HIV)-related neurological disorders (10, 2.8%). Other focal/systemic infections with neurological manifestations were diagnosed in an additional 60 (17.1%) cases. The leading noncommunicable conditions were epilepsy (61, 17.3%), psychiatric disorders (56, 16.0%), and cerebrovascular accident (23, 6.6%). Overall fatality rate was 8.2% (29/351), but up to 23.8% for CNS infections. Sequelae were observed in 76 (21.6%) patients. Clinical presentations and etiologies of neurological disorders were very diverse in this rural Central African setting and caused considerable mortality and morbidity.

Cancers of the Brain and CNS: Global Patterns and Trends in Incidence.

Science.gov (United States)

Mortazavi, S M J; Mortazavi, S A R; Paknahad, M

2018-03-01

Miranda-Filho et al. in their recently published paper entitled "Cancers of the brain and CNS: global patterns and trends in incidence" provided a global status report of the geographic and temporal variations in the incidence of brain and CNS cancers in different countries across continents worldwide. While the authors confirm the role of genetic risk factors and ionizing radiation exposures, they claimed that no firm conclusion could be drawn about the role of exposure to non-ionizing radiation. The paper authored by Miranda-Filho et al. not only addresses a challenging issue, it can be considered as a good contribution in the field of brain and CNS cancers. However, our correspondence addresses a basic shortcoming of this paper about the role of electromagnetic fields and cancers and provides evidence showing that exposure to radiofrequency electromagnetic fields (RF-EMFs), at least at high levels and long durations, can increases the risk of cancer.

The Coordinated Noninvasive Studies (CNS) Project. Phase 1

Science.gov (United States)

1991-12-01

subjects with a periSylvian HA in this range, all have indications of subtle neurological dysfunction: JLM mild learning disorder; mild dyslexia JS...made available, it is possible that "early intervention " techniques might be developed that could relieve these individuals of their terrible...mild dyslexia , 2) stuttering, 3) central auditory dysfunction, and 4) hyperactivity/ substance addiction. Plante and colleagues (see references) have

Stability of Early Risk Assessment for Autism Spectrum Disorder in Preterm Infants

Science.gov (United States)

Yaari, Maya; Yitzhak, Neta; Harel, Ayelet; Friedlander, Edwa; Bar-Oz, Benjamin; Eventov-Friedman, Smadar; Mankuta, David; Gamliel, Ifat; Yirmiya, Nurit

2016-01-01

Stability and change in early autism spectrum disorder risk were examined in a cohort of 99 preterm infants (?34 weeks of gestation) using the Autism Observation Scale for Infants at 8 and 12 months and the Autism Diagnostic Observation Schedule--Toddler Module at 18 months. A total of 21 infants were identified at risk by the Autism Observation…

Abnormal early gamma responses to emotional faces differentiate unipolar from bipolar disorder patients.

Science.gov (United States)

Liu, T Y; Chen, Y S; Su, T P; Hsieh, J C; Chen, L F

2014-01-01

This study investigates the cortical abnormalities of early emotion perception in patients with major depressive disorder (MDD) and bipolar disorder (BD) using gamma oscillations. Twenty-three MDD patients, twenty-five BD patients, and twenty-four normal controls were enrolled and their event-related magnetoencephalographic responses were recorded during implicit emotional tasks. Our results demonstrated abnormal gamma activity within 100 ms in the emotion-related regions (amygdala, orbitofrontal (OFC) cortex, anterior insula (AI), and superior temporal pole) in the MDD patients, suggesting that these patients may have dysfunctions or negativity biases in perceptual binding of emotional features at very early stage. Decreased left superior medial frontal cortex (smFC) responses to happy faces in the MDD patients were correlated with their serious level of depression symptoms, indicating that decreased smFC activity perhaps underlies irregular positive emotion processing in depressed patients. In the BD patients, we showed abnormal activation in visual regions (inferior/middle occipital and middle temporal cortices) which responded to emotional faces within 100 ms, supporting that the BD patients may hyperactively respond to emotional features in perceptual binding. The discriminant function of gamma activation in the left smFC, right medial OFC, right AI/inferior OFC, and the right precentral cortex accurately classified 89.6% of patients as unipolar/bipolar disorders.

Fetal Alcohol Spectrum Disorder: Potential Role of Endocannabinoids Signaling

Directory of Open Access Journals (Sweden)

Balapal S. Basavarajappa

2015-10-01

Full Text Available One of the unique features of prenatal alcohol exposure in humans is impaired cognitive and behavioral function resulting from damage to the central nervous system (CNS, which leads to a spectrum of impairments referred to as fetal alcohol spectrum disorder (FASD. Human FASD phenotypes can be reproduced in the rodent CNS following prenatal ethanol exposure. Several mechanisms are expected to contribute to the detrimental effects of prenatal alcohol exposure on the developing fetus, particularly in the developing CNS. These mechanisms may act simultaneously or consecutively and differ among a variety of cell types at specific developmental stages in particular brain regions. Studies have identified numerous potential mechanisms through which alcohol can act on the fetus. Among these mechanisms are increased oxidative stress, mitochondrial damage, interference with the activity of growth factors, glia cells, cell adhesion molecules, gene expression during CNS development and impaired function of signaling molecules involved in neuronal communication and circuit formation. These alcohol-induced deficits result in long-lasting abnormalities in neuronal plasticity and learning and memory and can explain many of the neurobehavioral abnormalities found in FASD. In this review, the author discusses the mechanisms that are associated with FASD and provides a current status on the endocannabinoid system in the development of FASD.

Interaction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: A systematic review and meta-analysis.

Science.gov (United States)

Wang, Qingzhong; Shelton, Richard C; Dwivedi, Yogesh

2018-01-01

Gene-environment interaction contributes to the risks of psychiatric disorders. Interactions between FKBP5 gene variants and early-life stress may enhance the risk not only for mood disorder, but also for a number of other behavioral phenotypes. The aim of the present study was to review and conduct a meta-analysis on the results from published studies examining interaction between FKBP5 gene variants and early-life stress and their associations with stress-related disorders such as major depression and PTSD. A literature search was conducted using PsychINFO and PubMed databases until May 2017. A total of 14 studies with a pooled total of 15109 participants met the inclusion criteria, the results of which were combined and a meta-analysis was performed using the differences in correlations as the effect measure. Based on literature, rs1360780, rs3800373, and rs9470080 SNPs were selected within the FKBP5 gene and systematic review was conducted. Based on the Comprehensive Meta-Analysis software, no publication bias was detected. Sensitivity analysis and credibility of meta-analysis results also indicated that the analyses were stable. The meta-analysis showed that individuals who carry T allele of rs1360780, C-allele of rs3800373 or T-allele of rs9470080 exposed to early-life trauma had higher risks for depression or PTSD. The effects of ethnicity, age, sex, and different stress measures were not examined due to limited sample size. These results provide strong evidence of interactions between FKBP5 genotypes and early-life stress, which could pose a significant risk factor for stress-associated disorders such as major depression and PTSD. Copyright © 2017 Elsevier B.V. All rights reserved.

A safety assessment methodology applied to CNS/ATM-based air traffic control system

Energy Technology Data Exchange (ETDEWEB)

Vismari, Lucio Flavio, E-mail: lucio.vismari@usp.b [Safety Analysis Group (GAS), School of Engineering at University of Sao Paulo (Poli-USP), Av. Prof. Luciano Gualberto, Trav.3, n.158, Predio da Engenharia de Eletricidade, Sala C2-32, CEP 05508-900, Sao Paulo (Brazil); Batista Camargo Junior, Joao, E-mail: joaocamargo@usp.b [Safety Analysis Group (GAS), School of Engineering at University of Sao Paulo (Poli-USP), Av. Prof. Luciano Gualberto, Trav.3, n.158, Predio da Engenharia de Eletricidade, Sala C2-32, CEP 05508-900, Sao Paulo (Brazil)

2011-07-15

In the last decades, the air traffic system has been changing to adapt itself to new social demands, mainly the safe growth of worldwide traffic capacity. Those changes are ruled by the Communication, Navigation, Surveillance/Air Traffic Management (CNS/ATM) paradigm , based on digital communication technologies (mainly satellites) as a way of improving communication, surveillance, navigation and air traffic management services. However, CNS/ATM poses new challenges and needs, mainly related to the safety assessment process. In face of these new challenges, and considering the main characteristics of the CNS/ATM, a methodology is proposed at this work by combining 'absolute' and 'relative' safety assessment methods adopted by the International Civil Aviation Organization (ICAO) in ICAO Doc.9689 , using Fluid Stochastic Petri Nets (FSPN) as the modeling formalism, and compares the safety metrics estimated from the simulation of both the proposed (in analysis) and the legacy system models. To demonstrate its usefulness, the proposed methodology was applied to the 'Automatic Dependent Surveillance-Broadcasting' (ADS-B) based air traffic control system. As conclusions, the proposed methodology assured to assess CNS/ATM system safety properties, in which FSPN formalism provides important modeling capabilities, and discrete event simulation allowing the estimation of the desired safety metric.

A safety assessment methodology applied to CNS/ATM-based air traffic control system

International Nuclear Information System (INIS)

Vismari, Lucio Flavio; Batista Camargo Junior, Joao

2011-01-01

In the last decades, the air traffic system has been changing to adapt itself to new social demands, mainly the safe growth of worldwide traffic capacity. Those changes are ruled by the Communication, Navigation, Surveillance/Air Traffic Management (CNS/ATM) paradigm , based on digital communication technologies (mainly satellites) as a way of improving communication, surveillance, navigation and air traffic management services. However, CNS/ATM poses new challenges and needs, mainly related to the safety assessment process. In face of these new challenges, and considering the main characteristics of the CNS/ATM, a methodology is proposed at this work by combining 'absolute' and 'relative' safety assessment methods adopted by the International Civil Aviation Organization (ICAO) in ICAO Doc.9689 , using Fluid Stochastic Petri Nets (FSPN) as the modeling formalism, and compares the safety metrics estimated from the simulation of both the proposed (in analysis) and the legacy system models. To demonstrate its usefulness, the proposed methodology was applied to the 'Automatic Dependent Surveillance-Broadcasting' (ADS-B) based air traffic control system. As conclusions, the proposed methodology assured to assess CNS/ATM system safety properties, in which FSPN formalism provides important modeling capabilities, and discrete event simulation allowing the estimation of the desired safety metric.

Iron Oxide Magnetic Nanoparticles Highlight Early Involvement of the Choroid Plexus in Central Nervous System Inflammation

Directory of Open Access Journals (Sweden)

Jason M. Millward

2013-03-01

Full Text Available Neuroinflammation during multiple sclerosis involves immune cell infiltration and disruption of the BBB (blood–brain barrier. Both processes can be visualized by MRI (magnetic resonance imaging, in multiple sclerosis patients and in the animal model EAE (experimental autoimmune encephalomyelitis. We previously showed that VSOPs (very small superparamagnetic iron oxide particles reveal CNS (central nervous system lesions in EAE which are not detectable by conventional contrast agents in MRI. We hypothesized that VSOP may help detect early, subtle inflammatory events that would otherwise remain imperceptible. To investigate the capacity of VSOP to reveal early events in CNS inflammation, we induced EAE in SJL mice using encephalitogenic T-cells, and administered VSOP prior to onset of clinical symptoms. In parallel, we administered VSOP to mice at peak disease, and to unmanipulated controls. We examined the distribution of VSOP in the CNS by MRI and histology. Prior to disease onset, in asymptomatic mice, VSOP accumulated in the choroid plexus and in spinal cord meninges in the absence of overt inflammation. However, VSOP was undetectable in the CNS of non-immunized control mice. At peak disease, VSOP was broadly distributed; we observed particles in perivascular inflammatory lesions with apparently preserved glia limitans. Moreover, at peak disease, VSOP was prominent in the choroid plexus and was seen in elongated endothelial structures, co-localized with phagocytes, and diffusely disseminated in the parenchyma, suggesting multiple entry mechanisms of VSOP into the CNS. Thus, using VSOP we were able to discriminate between inflammatory events occurring in established EAE and, importantly, we identified CNS alterations that appear to precede immune cell infiltration and clinical onset.

Natural host genetic resistance to lentiviral CNS disease: a neuroprotective MHC class I allele in SIV-infected macaques.

Directory of Open Access Journals (Sweden)

Joseph L Mankowski

Full Text Available Human immunodeficiency virus (HIV infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and development of lentiviral-induced central nervous system (CNS disease using a well-characterized simian immunodeficiency (SIV/pigtailed macaque model. The risk of developing CNS disease (SIV encephalitis was 2.5 times higher for animals that did not express the MHC class I allele Mane-A*10 (P = 0.002; RR = 2.5. Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction in the CNS than Mane-A*10 negative animals (P<0.001. Mane-A*10 positive animals with the highest CNS viral burdens contained SIV gag escape mutants at the Mane-A*10-restricted KP9 epitope in the CNS whereas wild type KP9 sequences dominated in the brain of Mane-A*10 negative animals with comparable CNS viral burdens. These concordant findings demonstrate that particular MHC class I alleles play major neuroprotective roles in lentiviral-induced CNS disease.

Who says this is a modern disorder? The early history of attention deficit hyperactivity disorder

Science.gov (United States)

Martinez-Badía, Jose; Martinez-Raga, Jose

2015-01-01

Attention-deficit hyperactivity disorder (ADHD) is a complex, heterogeneous and multifactorial neurodevelopmental disorder characterized by persistent symptoms of inattention, hyperactivity and impulsivity. Although the first clinical description of a constellation of symptoms highly resembling to what currently could be diagnosed as ADHD is generally attributed to George F Still in 1902, there are scattered but significant published historical medical, scientific and non-scientific reports, much prior to Still’s lectures, of what is currently conceptualized as ADHD. The present report aimed at exploring the early history of ADHD, prior to the 20th century in the medical literature and in other historical sources, to provide clinicians, researchers and other professionals with a better understanding of the roots and current conceptualization of this disorder. It is possible to find clues and highly suggestive descriptions of individuals presenting symptoms resembling what is currently defined as ADHD in the literature, in paintings or in the Bible. However, the earliest medical reports of individuals with abnormal degrees of inattention, distractibility and overactivity date from the last quarter of the 18th century, included in two of the first textbooks specifically on the subject of mental diseases, published by the German Melchior Adam Weikard and the Scottish Sir Alexander Crichton. During the 19th century some eminent physicians from Germany, France or Great Britain, such as Charles West, Thomas C Albutt, Thomas S Clouston, William W, Ireland, John Haslam, Heinrich Neumann, or Désiré-Magloire Bourneville, among others provided clinical depictions of patients that most likely presently would be diagnosed as having ADHD. Whilst some of the children described by Still and his predecessors may have suffered from a variety of neurological and psychiatric disorders, many of these patients showed clear symptoms of ADHD and may present with comorbid disorders, as

Social Learning Family Therapy and the Treatment of Conduct Disorder in Early Childhood: Premise, Procedures and Prospects.

Science.gov (United States)

Mpofu, Elias

1997-01-01

Discusses social learning family therapy hypotheses on the development and sustenance of conduct disorder in early childhood, together with treatment approaches that use parents as the primary agents of change. Reviews research showing that parent training procedures hold much promise for the treatment of conduct disorder in childhood. (JPB)

Neural Mechanisms of Early-Life Social Stress as a Developmental Risk Factor for Severe Psychiatric Disorders.

Science.gov (United States)

Reinwald, Jonathan Rochus; Becker, Robert; Mallien, Anne Stephanie; Falfan-Melgoza, Claudia; Sack, Markus; Clemm von Hohenberg, Christian; Braun, Urs; Cosa Linan, Alejandro; Gass, Natalia; Vasilescu, Andrei-Nicolae; Tollens, Fabian; Lebhardt, Philipp; Pfeiffer, Natascha; Inta, Dragos; Meyer-Lindenberg, Andreas; Gass, Peter; Sartorius, Alexander; Weber-Fahr, Wolfgang

2017-12-28

To explore the domain-general risk factor of early-life social stress in mental illness, rearing rodents in persistent postweaning social isolation has been established as a widely used animal model with translational relevance for neurodevelopmental psychiatric disorders such as schizophrenia. Although changes in resting-state brain connectivity are a transdiagnostic key finding in neurodevelopmental diseases, a characterization of imaging correlates elicited by early-life social stress is lacking. We performed resting-state functional magnetic resonance imaging of postweaning social isolation rats (N = 23) 9 weeks after isolation. Addressing well-established transdiagnostic connectivity changes of psychiatric disorders, we focused on altered frontal and posterior connectivity using a seed-based approach. Then, we examined changes in regional network architecture and global topology using graph theoretical analysis. Seed-based analyses demonstrated reduced functional connectivity in frontal brain regions and increased functional connectivity in posterior brain regions of postweaning social isolation rats. Graph analyses revealed a shift of the regional architecture, characterized by loss of dominance of frontal regions and emergence of nonfrontal regions, correlating to our behavioral results, and a reduced modularity in isolation-reared rats. Our result of functional connectivity alterations in the frontal brain supports previous investigations postulating social neural circuits, including prefrontal brain regions, as key pathways for risk for mental disorders arising through social stressors. We extend this knowledge by demonstrating more widespread changes of brain network organization elicited by early-life social stress, namely a shift of hubness and dysmodularity. Our results highly resemble core alterations in neurodevelopmental psychiatric disorders such as schizophrenia, autism, and attention-deficit/hyperactivity disorder in humans. Copyright © 2017

CD11c-expressing cells affect Treg behavior in the meninges during CNS infection1

Science.gov (United States)

O’Brien, Carleigh A.; Overall, Christopher; Konradt, Christoph; O’Hara Hall, Aisling C.; Hayes, Nikolas W.; Wagage, Sagie; John, Beena; Christian, David A.; Hunter, Christopher A.; Harris, Tajie H.

2017-01-01

Treg cells play an important role in the CNS during multiple infections as well as autoimmune inflammation, but the behavior of this cell type in the CNS has not been explored. In mice, infection with Toxoplasma gondii leads to a Th1-polarized parasite-specific effector T cell response in the brain. Similarly, the Treg cells in the CNS during T. gondii infection are Th1-polarized, exemplified by T-bet, CXCR3, and IFN-γ expression. Unlike effector CD4+ T cells, an MHC Class II tetramer reagent specific for T. gondii did not recognize Treg cells isolated from the CNS. Likewise, TCR sequencing revealed minimal overlap in TCR sequence between effector and regulatory T cells in the CNS. Whereas effector T cells are found in the brain parenchyma where parasites are present, Treg cells were restricted to the meninges and perivascular spaces. The use of intravital imaging revealed that activated CD4+ T cells within the meninges were highly migratory, while Treg cells moved more slowly and were found in close association with CD11c+ cells. To test whether the behavior of Tregs in the meninges is influenced by interactions with CD11c+ cells, mice were treated with anti-LFA-1 antibodies to reduce the number of CD11c+ cells in this space. The anti-LFA-1 treatment led to fewer contacts between Tregs and the remaining CD11c+ cells and increased the speed of Treg cell migration. These data suggest that Treg cells are anatomically restricted within the CNS and the interaction with CD11c+ populations regulates their local behavior during T. gondii infection. PMID:28389591

Elevated interferon-gamma in CNS inflammatory disease: a potential complication for bone marrow reconstitution in MS

DEFF Research Database (Denmark)

Hassan-Zahraee, M; Tran, E H; Bourbonnière, L

2000-01-01

but levels were higher in IFNgamma transgenics. BM transplantation into IFNgamma-deficient recipients also had a high failure rate. Transplants of BM from mice lacking expression of IFNgamma-receptor failed, whereas IFNgamma-deficient grafts survived, suggesting that IFNgamma response status of the graft can......Bone marrow transplantation (BMT) is increasingly used to treat Multiple Sclerosis (MS) a CNS inflammatory disease with elevated CNS and systemic IFNgamma levels. We wished to determine the effect of IFNgamma on BM graft survival in a transgenic mouse model for chronic MS. BM transplantation...... into transgenic mice which express elevated levels of IFNgamma in the CNS was unsuccessful. By contrast, there was 100% survival of even fully allogeneic, T-depleted transplants to transgenics that over express TNFalpha in the CNS, using the same MBP promoter. IFNgamma was detectable in spleen of irradiated mice...

Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson’s disease

Science.gov (United States)

Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A.; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A.; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C.; Mackay, Clare E.

2016-01-01

Abstract See Postuma (doi:10.1093/aww131) for a scientific commentary on this article. Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson’s disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson’s disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson’s disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson’s disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson’s disease and 10 control subjects received 123I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye

The Influence of Maternal Prenatal and Early Childhood Nutrition and Maternal Prenatal Stress on Offspring Immune System Development and Neurodevelopmental Disorders

Directory of Open Access Journals (Sweden)

Andrea Horvath Marques

2013-07-01

Full Text Available The developing immune system and central nervous system in the fetus and child are extremely sensitive to both exogenous and endogenous signals. Early immune system programming, leading to changes that can persist over the life course, has been suggested, and other evidence suggests that immune dysregulation in the early developing brain may play a role in neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. The timing of immune dysregulation with respect to gestational age and neurologic development of the fetus may shape the elicited response. This creates a possible sensitive window of programming or vulnerability. This review will explore the effects of prenatal maternal and infant nutritional status (from conception until early childhood as well as prenatal maternal stress and anxiety on early programming of immune function, and how this might influence neurodevelopment. We will describe fetal immune system development and maternal-fetal immune interactions to provide a better context for understanding the influence of nutrition and stress on the immune system. Finally, we will discuss the implications for prevention of neurodevelopmental disorders, with a focus on nutrition. Although certain micronutrient supplements have shown to both reduce the risk of neurodevelopmental disorders and enhance fetal immune development, we do not know whether their impact on immune development contributes to the preventive effect on neurodevelopmental disorders. Future studies are needed to elucidate this relationship, which may contribute to a better understanding of preventative mechanisms. Integrating studies of neurodevelopmental disorders and prenatal exposures with the simultaneous evaluation of neural and immune systems will shed light on mechanisms that underlie individual vulnerability or resilience to neurodevelopmental disorders and ultimately contribute to the development of primary preventions and early

Distinctive response of CNS glial cells in oro-facial pain associated with injury, infection and inflammation

Directory of Open Access Journals (Sweden)

Ribeiro-da-Silva Alfredo

2010-11-01

Full Text Available Abstract Oro-facial pain following injury and infection is frequently observed in dental clinics. While neuropathic pain evoked by injury associated with nerve lesion has an involvement of glia/immune cells, inflammatory hyperalgesia has an exaggerated sensitization mediated by local and circulating immune mediators. To better understand the contribution of central nervous system (CNS glial cells in these different pathological conditions, in this study we sought to characterize functional phenotypes of glial cells in response to trigeminal nerve injury (loose ligation of the mental branch, infection (subcutaneous injection of lipopolysaccharide-LPS and to sterile inflammation (subcutaneous injection of complete Freund's adjuvant-CFA on the lower lip. Each of the three insults triggered a specific pattern of mechanical allodynia. In parallel with changes in sensory response, CNS glial cells reacted distinctively to the challenges. Following ligation of the mental nerve, both microglia and astrocytes in the trigeminal nuclear complex were highly activated, more prominent in the principal sensory nucleus (Pr5 and subnucleus caudalis (Sp5C area. Microglial response was initiated early (days 3-14, followed by delayed astrocytes activation (days 7-28. Although the temporal profile of microglial and astrocyte reaction corresponded respectively to the initiation and chronic stage of neuropathic pain, these activated glial cells exhibited a low profile of cytokine expression. Local injection of LPS in the lower lip skin also triggered a microglial reaction in the brain, which started in the circumventricular organs (CVOs at 5 hours post-injection and diffused progressively into the brain parenchyma at 48 hours. This LPS-induced microglial reaction was accompanied by a robust induction of IκB-α mRNA and pro-inflammatory cytokines within the CVOs. However, LPS induced microglial activation did not specifically occur along the pain signaling pathway. In

Early Intervention Experiences of Families of Children with an Autism Spectrum Disorder: A Qualitative Pilot Study

Science.gov (United States)

Grygas Coogle, Christan; Guerette, Amy R.; Hanline, Mary Frances

2013-01-01

The purpose of this study was to obtain an understanding of the unique experiences of families who have a young child at risk for or identified with an autism spectrum disorder and their experiences with early intervention. Thirty-nine parents of children with or at risk for an autism spectrum disorder receiving Part C services in a state in the…

CNS-targets in control of energy and glucose homeostasis.

Science.gov (United States)

Kleinridders, André; Könner, A Christine; Brüning, Jens C

2009-12-01

The exceeding efforts in understanding the signals initiated by nutrients and hormones in the central nervous system (CNS) to regulate glucose and energy homeostasis have largely revolutionized our understanding of the neurocircuitry in control of peripheral metabolism. The ability of neurons to sense nutrients and hormones and to adopt a coordinated response to these signals is of crucial importance in controlling food intake, energy expenditure, glucose and lipid metabolism. Anatomical lesion experiments, pharmacological inhibition of signaling pathways, and, more recently, the analysis of conditional mouse mutants with modifications of hormone and nutrient signaling in defined neuronal populations have broadened our understanding of these complex neurocircuits. This review summarizes recent findings regarding the role of the CNS in sensing and transmitting nutritional and hormonal signals to control energy and glucose homeostasis and aims to define them as potential novel drug targets for the treatment of obesity and type 2 diabetes mellitus.

[The Influence of Media Consumption During Early Childhood on Media Use and Psychological Disorders in Adolescence].

Science.gov (United States)

Grund, Julius; Schulz, Wolfgang

2017-10-01

The Influence of Media Consumption During Early Childhood on Media Use and Psychological Disorders in Adolescence There are many studies that suggest that there is a link between high media consumption and psychological, physiological and social disorders. Nevertheless, there are also inconsistent results, methodical limitations and a lack of longitudinal studies. The present study analyses habits of media consumption in children and adolescents, the influence of different early childhood risk factors on the use of the media in adolescence and the links between early childhood media consumption and disorders in adolescence. The source of the data is the longitudinal project Future Family III. 249 families participated in the last data collection in the adolescence. Adolescents use the media more than five hours per day on average, nearly fifty percent of these adolescents can be considered as internet addicted and a majority consumes violent contents. A low socioeconomic status, low socio-emotional competences and low intelligence of the child as well as unfavorable educational style and psychological stress of the mother are risk factors for the media use in adolescence. Adolescents with a migration background have an increased risk of internet and computer game dependency. On the other hand, the overall utilization of media in the early childhood has only a low predictive power. The results indicate that these connections seem to be more complex than assumed. There is a need for more longitudinal studies in order to get a better understanding of the consequences of media consumption.

Versatile robotic interface to evaluate, enable and train locomotion and balance after neuromotor disorders

NARCIS (Netherlands)

Dominici, Nadia; Keller, Urs; Vallery, Heike; Friedli, Lucia; van den Brand, Rubia; Starkey, Michelle L; Musienko, Pavel; Riener, Robert; Courtine, Grégoire

Central nervous system (CNS) disorders distinctly impair locomotor pattern generation and balance, but technical limitations prevent independent assessment and rehabilitation of these subfunctions. Here we introduce a versatile robotic interface to evaluate, enable and train pattern generation and

Assessing early communication skills at 12 months: a retrospective study of Autism Spectrum Disorder.

Science.gov (United States)

Swain, Nathaniel Robert; Eadie, Patricia Ann; Prior, Margot Ruth; Reilly, Sheena

2015-07-01

Early identification of Autism Spectrum Disorder (ASD) is currently limited by the absence of reliable biological markers for the disorder, as well as the reliability of screening and assessment tools for children aged between 6 and 18 months. Ongoing research has demonstrated the importance of early social communication skills in differentiating children later diagnosed with ASD from their typically developing (TD) peers, but researchers have not yet investigated whether these differences can be detected using community-ascertained systematic observation data as early as 12 months. To investigate whether differences in early social communication skills can be detected at 12 months of age, comparing children later diagnosed with ASD, and TD peers; and to determine whether differences remain when groupings are based on age of subsequent ASD diagnosis. From a prospective community-ascertained sample, we collected data on children in early life, then conducted retrospective analyses for those children who were later diagnosed with ASD by the age of 7 years, compared with matched TD peers. We analysed standardized observational data of early communication skills, collected using the Communication and Symbolic Behavior Scales-Developmental Profile (CSBS-DP) Behavior Sample, when participants were 12 months of age. Children in the ASD group exhibited significantly lower social communication skills than the TD group, including on the Total score and Social and Symbolic Composite scores of the CSBS-DP Behavior Sample. Differences on the Total score and Social Composite were also detected for both early and late ASD diagnosis groups when compared with the TD group. These findings give further support for the importance of social communication in assessing children at risk of ASD as early as 12 months of age. Future research could evaluate the sensitivity and specificity of direct observation of these early communication skills as diagnostic indicators for ASD at 12 months

Pharmaco fMRI: Determining the functional anatomy of the effects of medication.

Science.gov (United States)

Wandschneider, Britta; Koepp, Matthias J

2016-01-01

Functional MRI studies have helped to elucidate underlying mechanisms in complex neurological and neuropsychiatric disorders. Disease processes often involve complex large-scale network interactions, extending beyond the presumed main disease focus. Given both the complexity of the clinical phenotype and the underlying dysfunctional brain circuits, so called pharmaco-fMRI (ph-MRI) studies probe pharmacological effects on functional neuro-anatomy, and can help to determine early treatment response, mechanisms of drug efficacy and side effects, and potentially advance CNS drug development. In this review, we discuss recent ph-MRI research in three major neuropsychiatric and neurological disorders and associated network alterations, namely selective serotonin and noradrenergic reuptake inhibitors in affective disorders and emotional processing circuits; antiepileptic drugs in epilepsy and cognitive networks; and stimulants in attention-deficit/hyperactivity disorder and networks of attention control. We conclude that ph-MRI studies show consistent and reproducible changes on disease relevant networks, and prove sensitive to early pharmacological effects on functional anatomy associated with disease. Further CNS drug research and development would benefit greatly from improved disease phenotyping, or biomarkers, using advanced imaging techniques.

The effect of IPS-modified, an early intervention for people with mood and anxiety disorders

DEFF Research Database (Denmark)

Hellström, Lone; Bech, Per; Nordentoft, Merete

2013-01-01

that Individual Placement and Support (IPS) has a positive effect on employment when provided to people with severe mental illness. This modified IPS intervention is aimed at supporting people with recently diagnosed anxiety or affective disorders in regaining their ability to work and facilitate their return......Anxiety and affective disorders can be disabling and have a major impact on the ability to work. In Denmark, people with a mental disorder, and mainly non-psychotic disorders, represent a substantial and increasing part of those receiving disability pensions. Previous studies have indicated...... to work or education.Aim: To investigate whether an early modified IPS intervention has an effect on employment and education when provided to people with recently diagnosed anxiety or affective disorders in a Danish context.Methods/design: The trial is a randomised, assessor-blinded, clinical superiority...

Differential diagnosis of neuromyelitis optica spectrum disorders

Science.gov (United States)

Kim, Sung-Min; Kim, Seong-Joon; Lee, Haeng Jin; Kuroda, Hiroshi; Palace, Jacqueline; Fujihara, Kazuo

2017-01-01

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disorder of the central nervous system (CNS) mostly manifesting as optic neuritis and/or myelitis, which are frequently recurrent/bilateral or longitudinally extensive, respectively. As the autoantibody to aquaporin-4 (AQP4-Ab) can mediate the pathogenesis of NMOSD, testing for the AQP4-Ab in serum of patients can play a crucial role in diagnosing NMOSD. Nevertheless, the differential diagnosis of NMOSD in clinical practice is often challenging despite the phenotypical and serological characteristics of the disease because: (1) diverse diseases with autoimmune, vascular, infectious, or neoplastic etiologies can mimic these phenotypes of NMOSD; (2) patients with NMOSD may only have limited clinical manifestations, especially in their early disease stages; (3) test results for AQP4-Ab can be affected by several factors such as assay methods, serologic status, disease stages, or types of treatment; (4) some patients with NMOSD do not have AQP4-Ab; and (5) test results for the AQP4-Ab may not be readily available for the acute management of patients. Despite some similarity in their phenotypes, these NMOSD and NMOSD-mimics are distinct from each other in their pathogenesis, prognosis, and most importantly treatment. Understanding the detailed clinical, serological, radiological, and prognostic differences of these diseases will improve the proper management as well as diagnosis of patients. PMID:28670343

Novel CNS drug discovery and development approach: model-based integration to predict neuro-pharmacokinetics and pharmacodynamics.

Science.gov (United States)

de Lange, Elizabeth C M; van den Brink, Willem; Yamamoto, Yumi; de Witte, Wilhelmus E A; Wong, Yin Cheong

2017-12-01

CNS drug development has been hampered by inadequate consideration of CNS pharmacokinetic (PK), pharmacodynamics (PD) and disease complexity (reductionist approach). Improvement is required via integrative model-based approaches. Areas covered: The authors summarize factors that have played a role in the high attrition rate of CNS compounds. Recent advances in CNS research and drug discovery are presented, especially with regard to assessment of relevant neuro-PK parameters. Suggestions for further improvements are also discussed. Expert opinion: Understanding time- and condition dependent interrelationships between neuro-PK and neuro-PD processes is key to predictions in different conditions. As a first screen, it is suggested to use in silico/in vitro derived molecular properties of candidate compounds and predict concentration-time profiles of compounds in multiple compartments of the human CNS, using time-course based physiology-based (PB) PK models. Then, for selected compounds, one can include in vitro drug-target binding kinetics to predict target occupancy (TO)-time profiles in humans. This will improve neuro-PD prediction. Furthermore, a pharmaco-omics approach is suggested, providing multilevel and paralleled data on systems processes from individuals in a systems-wide manner. Thus, clinical trials will be better informed, using fewer animals, while also, needing fewer individuals and samples per individual for proof of concept in humans.

Prevalence and risk factors of psychiatric disorders in early adolescence: 2004 Pelotas (Brazil) birth cohort.

Science.gov (United States)

La Maison, Carolina; Munhoz, Tiago N; Santos, Iná S; Anselmi, Luciana; Barros, Fernando C; Matijasevich, Alicia

2018-04-13

The present study aimed to evaluate the prevalence of psychiatric disorders in early adolescence, to examine the distribution of psychiatric disorders by maternal and child characteristics and to evaluate the occurrence of psychiatric comorbidities. This was a prospective cohort study of all live births in the city of Pelotas, Brazil, in 2004 (n = 4231). A total of 3562 subjects were evaluated at 11 years of age. Psychiatric disorders were assessed using the Development and Well-Being Assessment. Crude and adjusted logistic regression was used to investigate risk factors for any psychiatric disorder. According to DSM-5 criteria, the overall prevalence of psychiatric disorders was 13.2% (n = 471), 15.6% among the boys and 10.7% among the girls. The most common disorders were anxiety disorders (4.3%), any attention deficit/hyperactivity disorder (4.0%) and any conduct/oppositional disorder (2.8%). Low maternal education, smoking during pregnancy, the presence of moods symptoms during pregnancy or maternal chronic and severe depressive symptoms in the first years of the adolescent´s life, male gender, 5-min Apgar score mental health care services in this age group.

Meta-Analysis of Studies Incorporating the Interests of Young Children with Autism Spectrum Disorders into Early Intervention Practices

Directory of Open Access Journals (Sweden)

Carl J. Dunst

2012-01-01

Full Text Available Incorporating the interests and preferences of young children with autism spectrum disorders into interventions to promote prosocial behavior and decrease behavior excesses has emerged as a promising practice for addressing the core features of autism. The efficacy of interest-based early intervention practices was examined in a meta-analysis of 24 studies including 78 children 2 to 6 years of age diagnosed with autism spectrum disorders. Effect size analyses of intervention versus nonintervention conditions and high-interest versus low-interest contrasts indicated that interest-based intervention practices were effective in terms of increasing prosocial and decreasing aberrant child behavior. Additionally, interest-based interventions that focused on two of the three core features of autism spectrum disorders (poor communication, poor interpersonal relationships were found most effective in influencing child outcomes. Implications for very early intervention are discussed in terms addressing the behavior markers of autism spectrum disorders before they become firmly established.

Neurolymphomatosis: An International Primary CNS Lymphoma Collaborative Group report

NARCIS (Netherlands)

S. Grisariu (Sigal); B. Avni (Batia); T.T. Batchelor (Tracy); M.J. van den Bent (Martin); F. Bokstein (Felix); D. Schiff (David); O. Kuittinen (Outi); M.C. Chamberlain (Marc C.); P. Roth (Patrick); A. Nemets (Anatoly); E. Shalom (Edna); D. Ben-Yehuda (Dina); T. Siegal (Tali)

2010-01-01

textabstractNeurolymphomatosis (NL) is a rare clinical entity. The International Primary CNS Lymphoma Collaborative Group retrospectively analyzed 50 patients assembled from 12 centers in 5 countries over a 16-year period. NL was related to non-Hodgkin lymphoma in 90% and to acute leukemia in 10%.

Implication of coumarins towards central nervous system disorders.

Science.gov (United States)

Skalicka-Woźniak, Krystyna; Orhan, Ilkay Erdogan; Cordell, Geoffrey A; Nabavi, Seyed Mohammad; Budzyńska, Barbara

2016-01-01

Coumarins are widely distributed, plant-derived, 2H-1-benzopyran-2-one derivatives which have attracted intense interest in recent years as a result of their diverse and potent pharmacological properties. Particularly, their effects on the central nervous system (CNS) have been established. The present review discusses the most important pharmacological effects of natural and synthetic coumarins on the CNS, including their interactions with benzodiazepine receptors, their dopaminergic and serotonergic affinity, and their ability to inhibit cholinesterases and monoamine oxidases. The structure-activity relationships pertaining to these effects are also discussed. This review posits that natural or synthetic coumarins have the potential for development in the therapy of psychiatric and neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, schizophrenia, anxiety, epilepsy, and depression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Abnormal early brain responses during visual search are evident in schizophrenia but not bipolar affective disorder.

Science.gov (United States)

VanMeerten, Nicolaas J; Dubke, Rachel E; Stanwyck, John J; Kang, Seung Suk; Sponheim, Scott R

2016-01-01

People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia. Published by Elsevier B.V.

Regulation of Adult CNS Axonal Regeneration by the Post-transcriptional Regulator Cpeb1

Directory of Open Access Journals (Sweden)

Wilson Pak-Kin Lou

2018-01-01

Full Text Available Adult mammalian central nervous system (CNS neurons are unable to regenerate following axonal injury, leading to permanent functional impairments. Yet, the reasons underlying this regeneration failure are not fully understood. Here, we studied the transcriptome and translatome shortly after spinal cord injury. Profiling of the total and ribosome-bound RNA in injured and naïve spinal cords identified a substantial post-transcriptional regulation of gene expression. In particular, transcripts associated with nervous system development were down-regulated in the total RNA fraction while remaining stably loaded onto ribosomes. Interestingly, motif association analysis of post-transcriptionally regulated transcripts identified the cytoplasmic polyadenylation element (CPE as enriched in a subset of these transcripts that was more resistant to injury-induced reduction at the transcriptome level. Modulation of these transcripts by overexpression of the CPE binding protein, Cpeb1, in mouse and Drosophila CNS neurons promoted axonal regeneration following injury. Our study uncovered a global evolutionarily conserved post-transcriptional mechanism enhancing regeneration of injured CNS axons.

Detail Design of the hydrogen system and the gas blanketing system for the HANARO-CNS

International Nuclear Information System (INIS)

Choi, Jung Woon; Kim, Hark Rho; Kim, Young Ki; Wu, Sang Ik; Kim, Bong Su; Lee, Yong Seop

2007-04-01

The cold neutron source (CNS), which will be installed in the vertical CN hole of the reflector tank at HANARO, makes thermal neutrons to moderate into the cold neutrons with the ranges of 0.1 ∼ 10 meV passing through a moderator at about 22K. A moderator to produce cold neutrons is liquid hydrogen, which liquefies by the heat transfer with cryogenic helium flowing from the helium refrigeration system (HRS). Because of its installed location, the hydrogen system is designed to be surrounded by the gas blanketing system to notify the leakage on the system and to prevent hydrogen leakage out of the CNS. The hydrogen system, consisted of hydrogen charging unit, hydrogen storage unit, hydrogen buffer tank, and hydrogen piping, is designed to smoothly and safely supply hydrogen to and to draw back hydrogen from the IPA of the CNS under the HRS operation mode. Described is that calculation for total required hydrogen amount in the CNS as well as operation schemes of the hydrogen system. The gas blanketing system (GBS) is designed for the supply of the compressed nitrogen gas into the air pressurized valves for the CNS, to isolate the hydrogen system from the air and the water, and to prevent air or water intrusion into the vacuum system as well as the hydrogen system. All detail descriptions are shown inhere as well as the operation scheme for the GBS

Mast cell activation and neutrophil recruitment promotes early and robust inflammation in the meninges in EAE.

Science.gov (United States)

Christy, Alison L; Walker, Margaret E; Hessner, Martin J; Brown, Melissa A

2013-05-01

The meninges are often considered inert tissues that house the CSF and provide protection for the brain and spinal cord. Yet emerging data demonstrates that they are also active sites of immune responses. Furthermore, the blood-CSF barrier surrounding meningeal blood vessels, together with the blood-brain barrier (BBB), is postulated to serve as a gateway for the pathological infiltration of immune cells into the CNS in multiple sclerosis (MS). Our previous studies using mast cell-deficient (Kit(W/Wv)) mice demonstrated that mast cells resident in the dura mater and pia mater exacerbate experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, by facilitating CNS inflammatory cell influx. Here we examined the underlying mechanisms that mediate these effects. We demonstrate that there are dramatic alterations in immune associated gene expression in the meninges in pre-clinical disease, including those associated with mast cell and neutrophil function. Meningeal mast cells are activated within 24 h of disease induction, but do not directly compromise CNS vascular integrity. Rather, through production of TNF, mast cells elicit an early influx of neutrophils, cells known to alter vascular permeability, into the meninges. These data add to the growing evidence that inflammation in the meninges precedes CNS immune cell infiltration and establish that mast cells are among the earliest participants in these disease-initiating events. We hypothesize that mast cell-dependent neutrophil recruitment and activation in the meninges promotes early breakdown of the local BBB and CSF-blood barrier allowing initial immune cell access to the CNS. Copyright © 2012 Elsevier Ltd. All rights reserved.

Abbreviated exposure to hypoxia is sufficient to induce CNS dysmyelination, modulate spinal motor neuron composition, and impair motor development in neonatal mice.

Directory of Open Access Journals (Sweden)

Jens O Watzlawik

Full Text Available Neonatal white matter injury (nWMI is an increasingly common cause of cerebral palsy that results predominantly from hypoxic injury to progenitor cells including those of the oligodendrocyte lineage. Existing mouse models of nWMI utilize prolonged periods of hypoxia during the neonatal period, require complex cross-fostering and exhibit poor growth and high mortality rates. Abnormal CNS myelin composition serves as the major explanation for persistent neuro-motor deficits. Here we developed a simplified model of nWMI with low mortality rates and improved growth without cross-fostering. Neonatal mice are exposed to low oxygen from postnatal day (P 3 to P7, which roughly corresponds to the period of human brain development between gestational weeks 32 and 36. CNS hypomyelination is detectable for 2-3 weeks post injury and strongly correlates with levels of body and brain weight loss. Immediately following hypoxia treatment, cell death was evident in multiple brain regions, most notably in superficial and deep cortical layers as well as the subventricular zone progenitor compartment. PDGFαR, Nkx2.2, and Olig2 positive oligodendrocyte progenitor cell were significantly reduced until postnatal day 27. In addition to CNS dysmyelination we identified a novel pathological marker for adult hypoxic animals that strongly correlates with life-long neuro-motor deficits. Mice reared under hypoxia reveal an abnormal spinal neuron composition with increased small and medium diameter axons and decreased large diameter axons in thoracic lateral and anterior funiculi. Differences were particularly pronounced in white matter motor tracts left and right of the anterior median fissure. Our findings suggest that 4 days of exposure to hypoxia are sufficient to induce experimental nWMI in CD1 mice, thus providing a model to test new therapeutics. Pathological hallmarks of this model include early cell death, decreased OPCs and hypomyelination in early postnatal life

Flavonoids and the CNS

DEFF Research Database (Denmark)

Jäger, Anna Katharina; Saaby, Lasse

2011-01-01

Flavonoids are present in almost all terrestrial plants, where they provide UV-protection and colour. Flavonoids have a fused ring system consisting of an aromatic ring and a benzopyran ring with a phenyl substituent. The flavonoids can be divided into several classes depending on their structure....... Flavonoids are present in food and medicinal plants and are thus consumed by humans. They are found in plants as glycosides. Before oral absorption, flavonoids undergo deglycosylation either by lactase phloridzin hydrolase or cytosolic ß-glucocidase. The absorbed aglycone is then conjugated by methylation......, sulphatation or glucuronidation. Both the aglycones and the conjugates can pass the blood-brain barrier. In the CNS several flavones bind to the benzodiazepine site on the GABA(A)-receptor resulting in sedation, anxiolytic or anti-convulsive effects. Flavonoids of several classes are inhibitors of monoamine...

Interventions and Adaptations for Children with Autism Spectrum Disorder in Inclusive Early Childhood Settings

Science.gov (United States)

Brodzeller, Katharine L.; Ottley, Jennifer R.; Jung, Jeesun; Coogle, Christan G.

2018-01-01

The inclusive education of children with disabilities is considered best practice, yet many early childhood educators feel unprepared to deliver appropriate instruction for children with disabilities and often require supports to successfully meet the children's unique needs. Young children experiencing autism spectrum disorder are being diagnosed…

Visual orientation in hospitalized boys with early onset conduct disorder and borderline intellectual functioning

NARCIS (Netherlands)

van der Meere, Jacob; Börger, Norbert; Pirila, Silja

2012-01-01

The aim of the present study is to investigate visual orientation in hospitalized boys with severe early onset conduct disorder and borderline intellectual functioning. It is tested whether boys with the dual diagnosis have a stronger action-oriented response style to visual-cued go signals than the

A map of taste neuron projections in the Drosophila CNS

Indian Academy of Sciences (India)

2014-07-08

Jul 8, 2014 ... information that they represent. The extensive ... physiology and behaviour in the wild type and in these mutants .... taste information is processed in the CNS. 2. ..... gene affecting the specificity of the chemosensory neurons of.

Phantom limb pain: a case of maladaptive CNS plasticity?

DEFF Research Database (Denmark)

Flor, Herta; Nikolajsen, Lone; Jensen, Troels Staehelin

2006-01-01

might be a phenomenon of the CNS that is related to plastic changes at several levels of the neuraxis and especially the cortex. Here, we discuss the evidence for putative pathophysiological mechanisms with an emphasis on central, and in particular cortical, changes. We cite both animal and human...

Adolescent callous-unemotional traits and conduct disorder in adoptees exposed to severe early deprivation.

Science.gov (United States)

Kumsta, Robert; Sonuga-Barke, Edmund; Rutter, Michael

2012-03-01

There is a debate over whether disruptive behaviour should be regarded as a central component of, or rather as an epiphenomenon with little diagnostic value for, psychopathy. To test whether callous-unemotional traits and conduct disorder can be dissociated in the English and Romanian Adoptee Study, a prospective longitudinal study of adopted individuals with a history of severe early institutional deprivation. The Child and Adolescent Psychiatric Assessment was used to establish DSM-IV diagnoses for conduct disorder (and also oppositional defiant disorder) at the 15-year follow-up stage. The Inventory of Callous-Unemotional Traits questionnaire was administered to assess psychopathy traits. There was no significant association between callous-unemotional traits and conduct disorder, both according to parent and youth self-report assessed categorically and dimensionally after controlling for confounds. The majority of individuals with high callous-unemotional traits did not show conduct disorder in this special sample of children. This supports the view that, while common, an overlap between these aspects of psychopathology is not inevitable and so provides evidence for the dissociation of these two concepts. In terms of classification, we argue for a diagnostic scheme where psychopathy can be diagnosed independently of conduct disorder.

Fluids and barriers of the CNS: a historical viewpoint

Directory of Open Access Journals (Sweden)

Liddelow Shane A

2011-01-01

Full Text Available Abstract Tracing the exact origins of modern science can be a difficult but rewarding pursuit. It is possible for the astute reader to follow the background of any subject through the many important surviving texts from the classical and ancient world. While empirical investigations have been described by many since the time of Aristotle and scientific methods have been employed since the Middle Ages, the beginnings of modern science are generally accepted to have originated during the 'scientific revolution' of the 16th and 17th centuries in Europe. The scientific method is so fundamental to modern science that some philosophers consider earlier investigations as 'pre-science'. Notwithstanding this, the insight that can be gained from the study of the beginnings of a subject can prove important in the understanding of work more recently completed. As this journal undergoes an expansion in focus and nomenclature from cerebrospinal fluid (CSF into all barriers of the central nervous system (CNS, this review traces the history of both the blood-CSF and blood-brain barriers from as early as it was possible to find references, to the time when modern concepts were established at the beginning of the 20th century.

Omid Early Intervention Resource Kit for Children with Autism Spectrum Disorders and Their Families

Science.gov (United States)

Samadi, Sayyed Ali; Mahmoodizadeh, Ameneh

2014-01-01

Omid early intervention resource kit containing information booklets on autism spectrum disorders (ASD) and related issues, five packs of tangible selected playthings and communication facilitating aids was developed and evaluated with 65 Iranian parents. Beside a pretest before the resource kit deliverance, parents in the control group took part…

Potential Therapies by Stem Cell-Derived Exosomes in CNS Diseases: Focusing on the Neurogenic Niche

Directory of Open Access Journals (Sweden)

Alejandro Luarte

2016-01-01

Full Text Available Neurodegenerative disorders are one of the leading causes of death and disability and one of the biggest burdens on health care systems. Novel approaches using various types of stem cells have been proposed to treat common neurodegenerative disorders such as Alzheimer’s Disease, Parkinson’s Disease, or stroke. Moreover, as the secretome of these cells appears to be of greater benefit compared to the cells themselves, the extracellular components responsible for its therapeutic benefit have been explored. Stem cells, as well as most cells, release extracellular vesicles such as exosomes, which are nanovesicles able to target specific cell types and thus to modify their function by delivering proteins, lipids, and nucleic acids. Exosomes have recently been tested in vivo and in vitro as therapeutic conveyors for the treatment of diseases. As such, they could be engineered to target specific populations of cells within the CNS. Considering the fact that many degenerative brain diseases have an impact on adult neurogenesis, we discuss how the modulation of the adult neurogenic niches may be a therapeutic target of stem cell-derived exosomes. These novel approaches should be examined in cellular and animal models to provide better, more effective, and specific therapeutic tools in the future.

Inflammatory cytokines in the brain: does the CNS shape immune responses?

Science.gov (United States)

Owens, T; Renno, T; Taupin, V; Krakowski, M

1994-12-01

Immune responses in the central nervous system (CNS) have traditionally been regarded as representing the intrusion of an unruly, ill-behaved mob of leukocytes into the well-ordered and organized domain of thought and reason. However, results accumulated over the past few years suggest that, far from being an immunologically privileged organ, T lymphocytes may be regular and frequent visitors to the CNS, for purposes of immune surveillance. Here, Trevor Owens and colleagues propose that the brain itself can regulate or shape immune responses therein. Furthermore, given that the immune cells may be subverted to autoimmunity, they suggest that the study of inflammatory autoimmune disease in the brain may shed light on the ability of the local environment to regulate immune responses.

Malignant lymphoma in central nervous system (CNS)

International Nuclear Information System (INIS)

Fujiyoshi, Kenji; Fukuyama, Hidenao; Akiguchi, Ichiro; Kameyama, Masakuni; Nishimura, Toshio.

1984-01-01

A 71-year-old male was admitted to Kohka Public Hospital on January 4, 1980, because of frequent vomiting and recent memory loss. Two weeks before admission upper G-I series showed no abnormalities. Physical and neurological examinations revealed no abnormalities except for slightly apathetic appearance and recent memory loss. Mild pleocytosis and marked increase of protein in CSF were observed. CT scan on January 17 showed high density areas in both medial sides of temporal lobes with remarkable contrast enhancement. His memory and, consciousness disturbances gradually aggravated, accompanied by abnormal density spreading around the ventricle walls like ventriculitis. He was transfered to Kyoto University Hospital on March 17, and malignant lymphoma was diagnosed on the basis of CSF cytology. Radiation and chemotherapy alleviated the CNS involvement and he regained normal mental function. On June 16, he developed pneumonia followed by status epilepticus. Autopsy findings revealed no lymphoid cell infiltration, but fibrous tissues in both hippocampal gyri and lymphomatous cells in the liver, which could not be suspected on clinical examinations. Apparent malignant lymphoma cells were not found in lymph nodes. This case indicated peculiar evolution of malignant lymphoma from liver to CNS or vice versa. We could not decide which organ was primary. CT findings of this case was very interesting; they resembled ventriculitis, which simulate tumors such as medulloblastoma or ependymoma spreading under ependymal lining. (author)

A Novel Robust H∞ Filter Based on Krein Space Theory in the SINS/CNS Attitude Reference System

Directory of Open Access Journals (Sweden)

Fei Yu

2016-03-01

Full Text Available Owing to their numerous merits, such as compact, autonomous and independence, the strapdown inertial navigation system (SINS and celestial navigation system (CNS can be used in marine applications. What is more, due to the complementary navigation information obtained from two different kinds of sensors, the accuracy of the SINS/CNS integrated navigation system can be enhanced availably. Thus, the SINS/CNS system is widely used in the marine navigation field. However, the CNS is easily interfered with by the surroundings, which will lead to the output being discontinuous. Thus, the uncertainty problem caused by the lost measurement will reduce the system accuracy. In this paper, a robust H∞ filter based on the Krein space theory is proposed. The Krein space theory is introduced firstly, and then, the linear state and observation models of the SINS/CNS integrated navigation system are established reasonably. By taking the uncertainty problem into account, in this paper, a new robust H∞ filter is proposed to improve the robustness of the integrated system. At last, this new robust filter based on the Krein space theory is estimated by numerical simulations and actual experiments. Additionally, the simulation and experiment results and analysis show that the attitude errors can be reduced by utilizing the proposed robust filter effectively when the measurements are missing discontinuous. Compared to the traditional Kalman filter (KF method, the accuracy of the SINS/CNS integrated system is improved, verifying the robustness and the availability of the proposed robust H∞ filter.

Functional Recovery in Major Depressive Disorder: Providing Early Optimal Treatment for the Individual Patient

Science.gov (United States)

Katzman, Martin A; Habert, Jeffrey; McIntosh, Diane; MacQueen, Glenda M; Milev, Roumen V; McIntyre, Roger S; Blier, Pierre

2018-01-01

Abstract Major depressive disorder is an often chronic and recurring illness. Left untreated, major depressive disorder may result in progressive alterations in brain morphometry and circuit function. Recent findings, however, suggest that pharmacotherapy may halt and possibly reverse those effects. These findings, together with evidence that a delay in treatment is associated with poorer clinical outcomes, underscore the urgency of rapidly treating depression to full recovery. Early optimized treatment, using measurement-based care and customizing treatment to the individual patient, may afford the best possible outcomes for each patient. The aim of this article is to present recommendations for using a patient-centered approach to rapidly provide optimal pharmacological treatment to patients with major depressive disorder. Offering major depressive disorder treatment determined by individual patient characteristics (e.g., predominant symptoms, medical history, comorbidities), patient preferences and expectations, and, critically, their own definition of wellness provides the best opportunity for full functional recovery. PMID:29024974

SPARC and GluA1-Containing AMPA Receptors Promote Neuronal Health Following CNS Injury

Directory of Open Access Journals (Sweden)

Emma V. Jones

2018-02-01

Full Text Available The proper formation and maintenance of functional synapses in the central nervous system (CNS requires communication between neurons and astrocytes and the ability of astrocytes to release neuromodulatory molecules. Previously, we described a novel role for the astrocyte-secreted matricellular protein SPARC (Secreted Protein, Acidic and Rich in Cysteine in regulating α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs and plasticity at developing synapses. SPARC is highly expressed by astrocytes and microglia during CNS development but its level is reduced in adulthood. Interestingly, SPARC has been shown to be upregulated in CNS injury and disease. However, the role of SPARC upregulation in these contexts is not fully understood. In this study, we investigated the effect of chronic SPARC administration on glutamate receptors on mature hippocampal neuron cultures and following CNS injury. We found that SPARC treatment increased the number of GluA1-containing AMPARs at synapses and enhanced synaptic function. Furthermore, we determined that the increase in synaptic strength induced by SPARC could be inhibited by Philanthotoxin-433, a blocker of homomeric GluA1-containing AMPARs. We then investigated the effect of SPARC treatment on neuronal health in an injury context where SPARC expression is upregulated. We found that SPARC levels are increased in astrocytes and microglia following middle cerebral artery occlusion (MCAO in vivo and oxygen-glucose deprivation (OGD in vitro. Remarkably, chronic pre-treatment with SPARC prevented OGD-induced loss of synaptic GluA1. Furthermore, SPARC treatment reduced neuronal death through Philanthotoxin-433 sensitive GluA1 receptors. Taken together, this study suggests a novel role for SPARC and GluA1 in promoting neuronal health and recovery following CNS damage.

Nogo-A is a reliable oligodendroglial marker in adult human and mouse CNS and in demyelinated lesions

DEFF Research Database (Denmark)

Kuhlmann, Tanja; Remington, Leah; Maruschak, Brigitte

2007-01-01

to be strongly expressed in mature oligodendrocytes in vivo. In the present investigation we analyzed the expression patterns of Nogo-A in adult mouse and human CNS as well as in demyelinating animal models and multiple sclerosis lesions. Nogo-A expression was compared with that of other frequently used...... oligodendroglial markers such as CC1, CNP, and in situ hybridization for proteolipid protein mRNA. Nogo-A strongly and reliably labeled oligodendrocytes in the adult CNS as well as in demyelinating lesions and thus represents a valuable tool for the identification of oligodendrocytes in human and mouse CNS tissue...

The influence of ionizing radiation of high intensity on the functional status of monkey brain. Clinical picture of early postirradiation period

International Nuclear Information System (INIS)

Legeza, V.I.; Turlakov, Yu.S.

1990-01-01

In experiments with Macaca fascicularis a study was made of early manifestations of the central nervous system (CNS) disturbances caused by exposure to 24 MeV electrons (45 Gy). The results obtained permit us to distinguish two main ways (stereotypes) by which a clinical picture of early postirradiation period develops: comatose and noncomatose. A general clinical characteristic of each stereotype and stages of their development are presented. The postirradiation disturbances of nervous and psychis activity of monkeys are considered within the framework of the concept concerning acute reactions of exogenous type. It is suggested that the course of the early postirradiation period is conditioned by the involvement of some phylogenically determined, universal systemic mechanisms of the CNS response to external harmful effects

Tendencies the treatment of the central nervous system (CNS) tumors

International Nuclear Information System (INIS)

Alert Silva, Jose; Jimenez Medina, Jose

2004-01-01

It is known that the treatment of the central nervous system (CNS) tumors is based on the use of surgery and radiotherapy (RT) and that chemotherapy (QMT) is used even more, as well as the other drugs. A bibliographic review was made to update the knowledge on the current trends and perspectives of RT applied to CNS tumors. The following were found among them: a) combinations of RT and CMT; b) radiosensitizers incorporated to the radiant treatment; c) angiogenesis inhibitors associated with RT; d) the scale-up or increase of the RT doses thanks to the development of new technologies, such as 3 D conformal radiotherapy, intensity- modulated radiotherapy, surgery and others. Another field of research is that of the changes in the rhythm or fractioning of the RT: hyperfractionated, accelerated, combinations of both, etc., which will allow mainly to increase the dosage scale-up

Commercial viability of CNS drugs: balancing the risk/reward profile.

Science.gov (United States)

Johnson, Ginger S

2014-01-01

CNS has historically been a formidable therapeutic area in which to innovate owing to biological (e.g., complex neurobiology, difficulty reaching the target), as well as clinical (e.g., subjective clinical endpoints, high placebo response, lack of biomarkers) challenges. In the current market where many of the larger diseases are dominated by a generic standard of care, commercial challenges now make the triple threat of scientific-clinical-commercial risk too much for many players to tackle. However, opportunities do exist for smaller biotech companies to concentrate on narrowly focused patient populations associated with high unmet need for which risk can be tightly defined. In CNS, there are two major areas to balance the risk/reward profile and create commercially viable opportunities: To realize value, all companies (start-ups and big players) must define, measure and quantify clear and meaningful value to all stakeholders: physicians, patients, caregivers and payers. © 2013.

Metallothionein Expression and Roles During Neuropathology in the CNS

DEFF Research Database (Denmark)

Penkowa, Milena

2006-01-01

, their receptors and neurotrophins (TGFb, TGFb-Receptor, bFGF, bFGF-Receptor, VEGF, NT-3, NT-4/5, NGF); angiogenesis; and growth cone formation. Hence, MT-I+II enhance CNS tissue repair as seen clearly after the cryogenic injury, after which MT-I+II promote substitution of the necrotic lesion cavity with a glial...

Application of modelling and nanotechnology-based approaches: The emergence of breakthroughs in theranostics of central nervous system disorders.

Science.gov (United States)

Hassanzadeh, Parichehr; Atyabi, Fatemeh; Dinarvand, Rassoul

2017-08-01

The limited efficiency of the current treatment options against the central nervous system (CNS) disorders has created increasing demands towards the development of novel theranostic strategies. The enormous research efforts in nanotechnology have led to the production of highly-advanced nanodevices and biomaterials in a variety of geometries and configurations for targeted delivery of genes, drugs, or growth factors across the blood-brain barrier. Meanwhile, the richness or reliability of data, drug delivery methods, therapeutic effects or potential toxicity of nanoparticles, occurrence of the unexpected phenomena due to the polydisperse or polymorphic nature of nanomaterials, and personalized theranostics have remained as challenging issues. In this respect, computational modelling has emerged as a powerful tool for rational design of nanoparticles with optimized characteristics including the selectivity, improved bioactivity, and reduced toxicity that might lead to the effective delivery of therapeutic agents. High-performance simulation techniques by shedding more light on the dynamical behaviour of neural networks and pathomechanisms of CNS disorders may provide imminent breakthroughs in nanomedicine. In the present review, the importance of integration of nanotechnology-based approaches with computational techniques for targeted delivery of theranostics to the CNS has been highlighted. Copyright © 2017. Published by Elsevier Inc.

Endovascular transplantation of stem cells to the injured rat CNS

Energy Technology Data Exchange (ETDEWEB)

Lundberg, Johan; Soederman, Mikael; Andersson, Tommy; Holmin, Staffan [Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Department of Neuroradiology, Stockholm (Sweden); Le Blanc, Katarina [Karolinska University Hospital, Department of Stem Cell Research, Karolinska Institutet, Department of Clinical Immunology, Stockholm (Sweden)

2009-10-15

Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells. Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p<0.01) and 5 days (p<0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed. Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases. (orig.)

Endovascular transplantation of stem cells to the injured rat CNS

International Nuclear Information System (INIS)

Lundberg, Johan; Soederman, Mikael; Andersson, Tommy; Holmin, Staffan; Le Blanc, Katarina

2009-01-01

Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells. Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p<0.01) and 5 days (p<0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed. Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases. (orig.)

Usefulness of {sup 99m}Tc-ECD brain SPECT in acute onset pediatric CNS diseases. In comparison with CT and MRI

Energy Technology Data Exchange (ETDEWEB)

Hashimoto, Teisuke; Chikatsu, Hiroko; Nishiyama, Hiromune; Endo, Hiroko; Kono, Tatsuo; Iimura, Fumitoshi; Kuwashima, Shigeko; Saiki, Natoru; Fujioka, Mutsuhisa [Dokkyo Univ., Mibu, Tochigi (Japan). School of Medicine

2001-07-01

The purpose of this study was to assess the usefulness of regional cerebral blood flow (rCBF) measured by {sup 99m}Tc-L, L-ethyl cysteinate dimer (ECD) brain SPECT in the acute onset type of pediatric central nervous system (CNS) diseases. Thirteen children (7 girls, 6 boys, 4 month-12 years of age) who were diagnosed with 9 cases of viral encephalitis, two cases of febrile convulsion and one each of migraine and metabolic disorder underwent {sup 99m}Tc-ECD brain SPECT, CT and/or MRI within one week interval. The incidence of abnormal findings in the 13 patients was 96.4% (30/31) on {sup 99m}Tc-ECD brain SPECT, 17.6% (3/17) on CT and 63.6% (14/22) on MRI. The positive detection rate of {sup 99m}Tc-ECD brain SPECT was statistically (P<0.01 by a {chi}{sup 2} and/or Fisher's exact probability test) higher than those of CT and MRI. And the changes in rCBF were demonstrated. {sup 99m}Tc-ECD brain SPECT is a useful examination for the diagnosis and follow up management in patients with the acute onset type of pediatric CNS diseases. (author)

Primary CNS lymphoma as a cause of Korsakoff syndrome.

Science.gov (United States)

Toth, Cory; Voll, Chris; Macaulay, Robert

2002-01-01

Korsakoff syndrome presents with memory dysfunction with retrograde amnesia, anterograde amnesia, limited insight into dysfunction, and confabulation. The most common etiology of Korsakoff syndrome is thiamine deficiency secondary to alcoholism. There are limited case reports of structural lesions causing Korsakoff syndrome. A 46-year-old male with a long history of alcoholism presented with a history of confusion, amnesia, and confabulation with no localizing features on neurological examination. The patient showed no clinical change with intravenous thiamine. Computed tomography of the brain revealed a heterogenous, enhancing mass lesion centered within the third ventricle, with other lesions found throughout cortical and subcortical regions. The patient was given dexamethasone i.v. without noticeable clinical improvement but with marked radiological improvement with mass reduction. Stereotactic biopsy revealed a diagnosis of primary central nervous system (CNS) lymphoma. Most patients presenting with Korsakoff syndrome have thiamine deficiency; however, mass lesions can produce an identical clinical picture. This is the first case report of a patient with primary CNS lymphoma presenting as Korsakoff syndrome.

Early Markers of Autism Spectrum Disorders in Infants and Toddlers Prospectively Identified in the Social Attention and Communication Study

Science.gov (United States)

Barbaro, Josephine; Dissanayake, Cheryl

2013-01-01

The Social Attention and Communication Study involved the successful implementation of developmental surveillance of the early markers of autism spectrum disorders in a community-based setting. The objective in the current study was to determine the most discriminating and predictive markers of autism spectrum disorders used in the Social…

The Endocannabinoid System: A Dynamic Signalling System at the Crossroads Between Metabolism and Disease

NARCIS (Netherlands)

Witkamp, R.F.

2014-01-01

The discovery of the endocannabinoid system (ECS) in the early 1990s of last century generated high expectations of new therapeutic opportunities. Its central role and pleiotropic character seemed to offer promising indications in the fields of pain, inflammation, CNS disorders, weight management

Disturbed sleep and activity in toddlers with early signs of attention deficit hyperactivity disorder (ADHD)

DEFF Research Database (Denmark)

Bundgaard, Anne Katrine F.; Asmussen, Jette; Pedersen, Nadia S.

2018-01-01

This study investigated whether early signs of attention deficit hyperactivity disorder (ADHD) in toddlers aged 2-3 years are associated with disturbed sleep and activity levels. Participants were recruited from the Odense Child Cohort, and children scoring above the 93rd percentile on the ADHD...

Early discontinuation of attention-deficit/hyperactivity disorder drug treatment: a danish nationwide drug utilization study

DEFF Research Database (Denmark)

Pottegård, Anton; Bjerregaard, B. K.; Kortegaard, L. S.

2015-01-01

Knowledge of patterns of treatment discontinuation in attention-deficit/hyperactivity disorder (ADHD) drug treatment is of importance, for both the clinical practice and the study of long-term treatment outcomes. The purpose of this study was to describe early discontinuation of ADHD drug treatme...

A Pilot Study of a Culturally Adapted Early Intervention for Young Children with Autism Spectrum Disorders in China

Science.gov (United States)

Xu, Yun; Yang, Jian; Yao, Jing; Chen, Jun; Zhuang, Xiangxiang; Wang, Wenxiang; Zhang, Xiaoli; Lee, Gabrielle T.

2018-01-01

The purpose of this study was to pilot test the effects of a culturally adapted early intervention influenced by the Early Start Denver Model (ESDM) on reduction of autism symptoms and severity categorization for young children with autism spectrum disorders in China. Participants were randomly assigned to either the control or intervention…

Basal Ganglia Calcification with Tetanic Seizure Suggest Mitochondrial Disorder

OpenAIRE

Finsterer, Josef; Enzelsberger, Barbara; Bastowansky, Adam

2017-01-01

Patient: Female, 65 Final Diagnosis: Mitochondrial disorder Symptoms: Headache ? tetanic seizure Medication: Diazepam Clinical Procedure: Admission Specialty: Neurology Objective: Challenging differential diagnosis Background: Basal ganglia calcification (BGC) is a rare sporadic or hereditary central nervous system (CNS) abnormality, characterized by symmetric or asymmetric calcification of the basal ganglia. Case Report: We report the case of a 65-year-old Gypsy female who was admitted for a...

Comparing three forms of early intervention for youth with borderline personality disorder (the MOBY study): study protocol for a randomised controlled trial.

Science.gov (United States)

Chanen, Andrew; Jackson, Henry; Cotton, Sue M; Gleeson, John; Davey, Christopher G; Betts, Jennifer; Reid, Sophie; Thompson, Katherine; McCutcheon, Louise

2015-10-21

Borderline personality disorder is a severe mental disorder that usually has its onset in youth, but its diagnosis and treatment are often delayed. Psychosocial 'early intervention' is effective in improving symptoms and behaviours, but no trial has studied adaptive functioning as a primary outcome, even though this remains the major persistent impairment in this patient group. Also, the degree of complexity of treatment and requirements for implementation in mainstream health services are unclear. The primary aim of this trial is to evaluate the effectiveness of three forms of early intervention for borderline personality disorder in terms of adaptive functioning. Each treatment is defined by combining either a specialised or a general service delivery model with either an individual psychotherapy or a control psychotherapy condition. The study is a parallel-group, single-blind, randomised controlled trial, which has randomised permuted blocking, stratified by depression score, sex and age. The treatments are: (1) the specialised Helping Young People Early service model plus up to 16 sessions of individual cognitive analytic therapy; (2) the Helping Young People Early service plus up to 16 sessions of a control psychotherapy condition known as 'befriending'; (3) a general youth mental health care model plus up to 16 sessions of befriending. Participants will comprise 135 help-seeking youth aged 15-25 years with borderline personality disorder. After baseline assessment, staff blind to the study design and treatment group allocation will conduct assessments at 3, 6, 12 and 18 months. At the 12-month primary endpoint, the primary outcome is adaptive functioning (measures of social adjustment and interpersonal problems); secondary outcomes include measures of client satisfaction, borderline personality disorder features, depression and substance use. The results of this trial will help to clarify the comparative effectiveness of a specialised early intervention

CSF Hypocretin-1 Levels and Clinical Profiles in Narcolepsy and Idiopathic CNS Hypersomnia in Norway

Science.gov (United States)

Heier, Mona Skard; Evsiukova, Tatiana; Vilming, Steinar; Gjerstad, Michaela D.; Schrader, Harald; Gautvik, Kaare

2007-01-01

Objective: To evaluate the relationship between CSF hypocretin-1 levels and clinical profiles in narcolepsy and CNS hypersomnia in Norwegian patients. Method: CSF hypocretin-1 was measured by a sensitive radioimmunoassay in 47 patients with narcolepsy with cataplexy, 7 with narcolepsy without cataplexy, 10 with idiopathic CNS hypersomnia, and a control group. Results: Low hypocretin-1 values were found in 72% of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy. Patients with low CSF hypocretin-1 levels reported more extensive muscular involvement during cataplectic attacks than patients with normal levels. Hypnagogic hallucinations and sleep paralysis occurred more frequently in patients with cataplexy than in the other patient groups, but with no correlation to hypocretin-1 levels. Conclusion: About three quarters of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy had low CSF hypocretin-1 values, and appear to form a distinct clinical entity. Narcolepsy without cataplexy could not be distinguished from idiopathic CNS hypersomnia by clinical symptoms or biochemical findings. Citation: Heier MS; Evsiukova T; Vilming S; Gjerstad MD; Schrader H; Gautvik K. CSF hypocretin-1 levels and clinical profiles in narcolepsy and idiopathic CNS hypersomnia in norway. SLEEP 2007;30(8):969-973. PMID:17702265

Versatile robotic interface to evaluate, enable and train locomotion and balance after neuromotor disorders.

Science.gov (United States)

Dominici, Nadia; Keller, Urs; Vallery, Heike; Friedli, Lucia; van den Brand, Rubia; Starkey, Michelle L; Musienko, Pavel; Riener, Robert; Courtine, Grégoire

2012-07-01

Central nervous system (CNS) disorders distinctly impair locomotor pattern generation and balance, but technical limitations prevent independent assessment and rehabilitation of these subfunctions. Here we introduce a versatile robotic interface to evaluate, enable and train pattern generation and balance independently during natural walking behaviors in rats. In evaluation mode, the robotic interface affords detailed assessments of pattern generation and dynamic equilibrium after spinal cord injury (SCI) and stroke. In enabling mode,the robot acts as a propulsive or postural neuroprosthesis that instantly promotes unexpected locomotor capacities including overground walking after complete SCI, stair climbing following partial SCI and precise paw placement shortly after stroke. In training mode, robot-enabled rehabilitation, epidural electrical stimulation and monoamine agonists reestablish weight-supported locomotion, coordinated steering and balance in rats with a paralyzing SCI. This new robotic technology and associated concepts have broad implications for both assessing and restoring motor functions after CNS disorders, both in animals and in humans.

Early childhood adversities and risk of eating disorders in women: A Danish register-based cohort study.

Science.gov (United States)

Larsen, Janne Tidselbak; Munk-Olsen, Trine; Bulik, Cynthia M; Thornton, Laura M; Koch, Susanne Vinkel; Mortensen, Preben Bo; Petersen, Liselotte

2017-12-01

Previous studies evaluating the association between early childhood adversities and eating disorders have yielded conflicting results. The aim of this study is to examine the association between a range of adversities and risk of anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS) in 495,244 women. In this nationwide, register-based cohort study, nine types of early childhood adversity (family disruption, residential instability, placement in out-of-home care, familial death, parental somatic illness, parental psychiatric illness, parental disability, severe parental criminality, and parental substance use disorder) were defined and exposure during the first 6 years of life was determined. Hazard ratios for eating disorders were calculated using Cox regression. Few adversities were significantly associated with AN, and for each, the presence of the adversity was associated with lower risk for AN. BN, and EDNOS were positively associated with several types of adversities. AN rates were unchanged or reduced by up to 54% by adversities, whereas rates of BN and EDNOS were unchanged or increased by adversities by up to 49 and 89%, respectively. Our findings indicate that childhood adversities appear to be associated with an increased risk of BN and in particular EDNOS, whereas they seem to be either unassociated or associated with a decreased risk of AN. © 2017 Wiley Periodicals, Inc.

Lipidomics: the function of vital lipids in embryogenesis preventing autism spectrum disorders, treating sterile inflammatory diatheses with a lymphopoietic central nervous system component.

Science.gov (United States)

Tallberg, Thomas; Dabek, Jan; Hallamaa, Raija; Atroshi, Faik

2011-01-01

The central role performed by billions of vital central nervous system (CNS) lipids "lipidomics" in medical physiology is usually overlooked. A metabolic deficiency embracing these vital lipids can form the aetiology for a variety of diseases. CNS lipids regulate embryogenesis, cell induction, mental balance by preventing autism spectrum disorders, depression, burn-out syndromes like posttraumatic stress disease PTSD, by guarding normal immunity, treating sterile inflammatory diatheses with a titanium containing lymphopoietic CNS lipid component. The propaganda driving for unphysiological fat-free diets is dangerous and can cause serious health problems for a whole generation. This article presents a broad list of various mental and motor bodily functions of which the healthy function depends on these vital CNS lipids. A rigorous fat-free diet can provoke these metabolic lipid deficiencies but they can fortunately be compensated by dietary supplementation, but not by pharmacologic treatment.

Screening for autism spectrum disorder with the Early Childhood Inventory-4.

Science.gov (United States)

DeVincent, Carla; Gadow, Kenneth D; Strong, Greg; Schwartz, Joseph; Cuva, Simone

2008-02-01

The early identification of children with autism spectrum disorders (ASDs) is critical for the remediation of developmental deficits. This study examined the clinical utility of ASD scoring algorithms for the Early Childhood Inventory-4 (ECI-4), a DSM-IV-referenced rating scale, as a practical solution for screening 3- to 5-year-old children for ASD in medical and public school settings. Parents/teachers completed the ECI-4 for 3- to 5-year-old clinic referrals with an ASD (n = 196) or non-ASD psychiatric (n = 135) diagnosis. Children attending early childhood (i.e., day care, preschool, Head Start) programs were also rated by their parents (n = 507) and teachers (n = 407). Stepwise logistic regression was used to generate ASD scoring algorithms for the ECI-4. Receiver operating characteristic analyses generally indicated high levels of sensitivity/specificity for recommended ASD cutoff scores for parent (clinic: 0.96/0.80; preschool: 0.92/0.96) and teacher (clinic: 0.81/0.79; preschool: 0.97/0.92) ratings. Findings indicate that the ECI-4 shows promise as a clinically useful screening measure for ASD in clinic-referred and preschool children.

Pharmaco fMRI: Determining the functional anatomy of the effects of medication

Directory of Open Access Journals (Sweden)

Britta Wandschneider

2016-01-01

Full Text Available Functional MRI studies have helped to elucidate underlying mechanisms in complex neurological and neuropsychiatric disorders. Disease processes often involve complex large-scale network interactions, extending beyond the presumed main disease focus. Given both the complexity of the clinical phenotype and the underlying dysfunctional brain circuits, so called pharmaco-fMRI (ph-MRI studies probe pharmacological effects on functional neuro-anatomy, and can help to determine early treatment response, mechanisms of drug efficacy and side effects, and potentially advance CNS drug development. In this review, we discuss recent ph-MRI research in three major neuropsychiatric and neurological disorders and associated network alterations, namely selective serotonin and noradrenergic reuptake inhibitors in affective disorders and emotional processing circuits; antiepileptic drugs in epilepsy and cognitive networks; and stimulants in attention-deficit/hyperactivity disorder and networks of attention control. We conclude that ph-MRI studies show consistent and reproducible changes on disease relevant networks, and prove sensitive to early pharmacological effects on functional anatomy associated with disease. Further CNS drug research and development would benefit greatly from improved disease phenotyping, or biomarkers, using advanced imaging techniques.

Detection of anti-streptococcal, antienolase, and anti-neural antibodies in subjects with early-onset psychiatric disorders.

Science.gov (United States)

Nicolini, Humberto; López, Yaumara; Genis-Mendoza, Alma D; Manrique, Viana; Lopez-Canovas, Lilia; Niubo, Esperanza; Hernández, Lázaro; Bobes, María A; Riverón, Ana M; López-Casamichana, Mavil; Flores, Julio; Lanzagorta, Nuria; De la Fuente-Sandoval, Camilo; Santana, Daniel

2015-01-01

Infection with group A Streptococcus (StrepA) can cause post-infectious sequelae, including a spectrum of childhood-onset obsessive-compulsive (OCD) and tic disorders with autoimmune origin (PANDAS, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections). Until now, no single immunological test has been designed that unequivocally diagnoses these disorders. In this study, we assessed the detection of serum antibodies against human brain enolase (AE), neural tissue (AN) and Streptococcus (AS) as a laboratory tool for the diagnosis of early-onset psychiatric disorders. Serum antibodies against human brain enolase, total brain proteins, and total proteins from StrepA were detected by ELISA in 37 patients with a presumptive diagnosis of PANDAS and in 12 healthy subjects from Mexico and Cuba. The antibody titers against human brain enolase (AE) and Streptococcal proteins (AS) were higher in patients than in control subjects (t-student, tAE=-2.17, P=0.035; tAS=-2.68, P=0.01, n=12 and 37/group, df=47, significance level 0.05), while the neural antibody titers did not differ between the two groups (P(t)=0.05). The number of subjects (titers> meancontrol + CI95) with simultaneous seropositivity to all three antibodies was higher in the patient group (51.4%) than in the control group (8.3%) group (X2=5.27, P=0.022, df=1, n=49). The simultaneous detection of all three of these antibodies could provide valuable information for the etiologic diagnosis of individuals with early-onset obsessive-compulsive disorders associated with streptococcal infection and, consequently, for prescribing suitable therapy.

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

NARCIS (Netherlands)

Sturm, Dominik; Orr, Brent A.; Toprak, Umut H.; Hovestadt, Volker; Jones, David T. W.; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A.; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J.; Balasubramanian, Gnanaprakash; Worst, Barbara C.; Pajtler, Kristian W.; Brabetz, Sebastian; Johann, Pascal D.; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M.; Remke, Marc; Phillips, Joanna J.; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C.; Schniederjan, Matthew J.; Santi, Mariarita; Buccoliero, Anna M.; Dahiya, Sonika; Kramm, Christof M.; von Bueren, André O.; von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C.; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V. Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U.; Shalaby, Tarek; Grotzer, Michael; van Meter, Timothy; Monoranu, Camelia-Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S.; Taylor, Michael D.; Jones, Chris; Jabado, Nada; Karajannis, Matthias A.; Eils, Roland; Schlesner, Matthias; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M.; Ellison, David W.; Korshunov, Andrey; Kool, Marcel

2016-01-01

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

NARCIS (Netherlands)

Sturm, Dominik; Orr, Brent A.; Toprak, Umut H.; Hovestadt, Volker; Jones, David T W; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A.; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J.; Balasubramanian, Gnanaprakash; Worst, Barbara C.; Pajtler, Kristian W.; Brabetz, Sebastian; Johann, Pascal D.; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M.; Remke, Marc; Phillips, Joanna J.; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C.; Schniederjan, Matthew J.; Santi, Mariarita; Buccoliero, Anna M.; Dahiya, Sonika; Kramm, Christof M.; Von Bueren, André O.; Von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C.; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V. Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U.; Shalaby, Tarek; Grotzer, Michael; Van Meter, Timothy; Monoranu, Camelia Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; Van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S.; Taylor, Michael D.; Jones, Chris; Jabado, Nada; Karajannis, Matthias A.; Eils, Roland; Schlesner, Matthias; Lichter, Peter; Von Deimling, Andreas; Pfister, Stefan M.; Ellison, David W.; Korshunov, Andrey; Kool, Marcel

2016-01-01

Summary Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of

CNS germinomas are characterized by global demethylation, chromosomal instability and mutational activation of the Kit-, Ras/Raf/Erk- and Akt-pathways

Science.gov (United States)

Schulte, Simone Laura; Waha, Andreas; Steiger, Barbara; Denkhaus, Dorota; Dörner, Evelyn; Calaminus, Gabriele; Leuschner, Ivo; Pietsch, Torsten

2016-01-01

CNS germinomas represent a unique germ cell tumor entity characterized by undifferentiated tumor cells and a high response rate to current treatment protocols. Limited information is available on their underlying genomic, epigenetic and biological alterations. We performed a genome-wide analysis of genomic copy number alterations in 49 CNS germinomas by molecular inversion profiling. In addition, CpG dinucleotide methylation was studied by immunohistochemistry for methylated cytosine residues. Mutational analysis was performed by resequencing of candidate genes including KIT and RAS family members. Ras/Erk and Akt pathway activation was analyzed by immunostaining with antibodies against phospho-Erk, phosho-Akt, phospho-mTOR and phospho-S6. All germinomas coexpressed Oct4 and Kit but showed an extensive global DNA demethylation compared to other tumors and normal tissues. Molecular inversion profiling showed predominant genomic instability in all tumors with a high frequency of regional gains and losses including high level gene amplifications. Activating mutations of KIT exons 11, 13, and 17 as well as a case with genomic KIT amplification and activating mutations or amplifications of RAS gene family members including KRAS, NRAS and RRAS2 indicated mutational activation of crucial signaling pathways. Co-activation of Ras/Erk and Akt pathways was present in 83% of germinomas. These data suggest that CNS germinoma cells display a demethylated nuclear DNA similar to primordial germ cells in early development. This finding has a striking coincidence with extensive genomic instability. In addition, mutational activation of Kit-, Ras/Raf/Erk- and Akt- pathways indicate the biological importance of these pathways and their components as potential targets for therapy. PMID:27391150

School Age Outcomes of Children with Autism Spectrum Disorder Who Received Community-Based Early Interventions.

Science.gov (United States)

Vinen, Zoe; Clark, Megan; Paynter, Jessica; Dissanayake, Cheryl

2018-05-01

This study followed children with Autism Spectrum Disorder (ASD) from early intervention into their early schooling years, when they were aged between 6 and 9 years, on autism symptom severity and cognitive functioning. The children, matched at pre-intervention, were compared on type of community provided service: 31 were in receipt of community-based group Early Start Denver Model and 28 had received other community provisions for ASD. Irrespective of groups, cognitive functioning was found to have significantly improved by school age compared to pre-intervention. Autism symptom severity increased during the same developmental period, seemingly driven by an increase in restricted and repetitive behaviours over time. In contrast, both groups displayed improved social affect by school age.

4th ENRI International Workshop on ATM/CNS

CERN Document Server

2017-01-01

This book is a compilation of selected papers from the 4th ENRI International Workshop on ATM/CNS (EIWAC2015). The work focuses on novel techniques for aviation infrastructure in air traffic management (ATM) and communications, navigation, surveillance, and informatics (CNSI) domains. The contents make valuable contributions to academic researchers, engineers in the industry, and regulators of aviation authorities. As well, readers will encounter new ideas for realizing a more efficient and safer aviation system. .

General movements : A window for early identification of children at high risk for developmental disorders

NARCIS (Netherlands)

Hadders-Algra, M

Detection of children with a developmental disorder, such as cerebral palsy, at an early age is notoriously difficult. Recently, a new form of neuromotor assessment of young infants was developed, based on the assessment of the quality of general movements (GMs). GMs are movements of the fetus and

Longitudinal changes in the antecedent and early manifest course of bipolar disorder-A narrative review of prospective studies.

Science.gov (United States)

Pfennig, Andrea; Leopold, Karolina; Ritter, Philipp; Böhme, Anne; Severus, Emanuel; Bauer, Michael

2017-05-01

Prospective study designs ideally allow patients to be followed from the first manifestations of the illness or even from an at-risk stage. It can thus provide data on the predictive value of changes in clinical symptomatology, cognition or further biological markers to broaden our understanding of the etiopathology and symptomatic trajectory of bipolar disorders. The scope of this narrative review is to summarize evidence from prospectively collected data on psychopathological and other clinical and biological changes in the early developmental course of bipolar disorders. The narrative review was based on a literature search conducted in February 2016 within the PubMed library for prospective study data of persons in antecedent and early manifest stages of manifest bipolar disorder published within the last 15 years. A total of 19 prospective studies were included. Regarding psychopathological features; personality, temperament and character traits as well as changes in sleep and circadian rhythm, the evidence suggests that risk factors for the development of bipolar disorder can already be described and should be studied further to understand their interaction, mediation with other factors and timing in the developmental process of bipolar disorder. Apart from the positive family history, childhood anxiety, sleep problems, subthreshold (hypo)manic symptoms and certain character traits/emotionality should be identified and monitored already in clinical practice as their presence likely increases risk of bipolar disorder. Up to date no substantiated evidence was found from prospective studies addressing cognitive features, life events, immunological parameters and morphological central nervous system changes as potential risk factors for bipolar disorder. For an improved understanding of episodic disorders, longitudinal data collection is essential. Since the etiology of bipolar disorders is complex, a number of potential risk factors have been proposed

A systematic review of early intensive intervention for autism spectrum disorders.

Science.gov (United States)

Warren, Zachary; McPheeters, Melissa L; Sathe, Nila; Foss-Feig, Jennifer H; Glasser, Allison; Veenstra-Vanderweele, Jeremy

2011-05-01

Early intensive behavioral and developmental interventions for young children with autism spectrum disorders (ASDs) may enhance developmental outcomes. To systematically review evidence regarding such interventions for children aged 12 and younger with ASDs. We searched Medline, PsycINFO, and ERIC (Education Resources Information Center) from 2000 to May 2010. Two reviewers independently assessed studies against predetermined inclusion/exclusion criteria. Two reviewers independently extracted data regarding participant and intervention characteristics, assessment techniques, and outcomes and assigned overall quality and strength-of-evidence ratings using predetermined criteria. Thirty-four unique studies met inclusion criteria. Seventeen studies were case series; 2 were randomized controlled trials. We rated 1 study as good quality, 10 as fair quality, and 23 as poor quality. The strength of the evidence overall ranged from insufficient to low. Studies of University of California Los Angeles/Lovaas-based interventions and variants reported clinically significant gains in language and cognitive skills in some children, as did 1 randomized controlled trial of an early intensive developmental intervention approach (the Early Start Denver Model). Specific parent-training approaches yielded gains in short-term language function and some challenging behaviors. Data suggest that subgroups of children displayed more prominent gains across studies, but participant characteristics associated with greater gains are not well understood. Studies of Lovaas-based approaches and early intensive behavioral intervention variants and the Early Start Denver Model resulted in some improvements in cognitive performance, language skills, and adaptive behavior skills in some young children with ASDs, although the literature is limited by methodologic concerns.

[A case of Neuro-Behçet's disease with early onset of bipolar mood disorder].

Science.gov (United States)

Nakano, Yuko; Hatanaka, Yuki; Ikebuchi, Emi; Shimizu, Teruo; Nanko, Shinichiro; Utsumii, Takeshi

2004-01-01

In this report, we describe a case of Neuro-Behçet's disease with early onset of bipolar mood disorder. A 53-year-old man with neuropathy including dysphasia and dyslalia developed bipolar mood disorder with anxiety, agitation, depressive mood, talkativeness, hyperkinesias, and appetite rise, and soon exhibited severe personality deterioration. Oral aphthae, cell proliferation and elevated IL-6 levels in spinal fluid, and the patient's clinical downhill course with remission and relapse in spite of good reaction to steroid preparation indicated the possibility of Neuro-Behçet's disease. Brain MRI showed clear swelling of the brain stem area, especially in the pons, in the active phase with low signal in T1-weighted images contrasting with clear high signal in T2-weighted images and FLAIR. At the time of remission, atrophy of the brain stem was shown. These findings were consistent with the view reported in recent years concerning the brain image of Neuro-Behçet's disease, which seemed to be useful for the differential diagnosis. This case manifested two outstanding clinical features. First, it showed bipolar mood swing or mixed state distinguishable from disinhibition or euphoria in deteriorated personality, which is common in this condition. A clear bipolar mood disorder has not been described until now in Neuro-Behçet's disease. Second, subclinical dysthymia or hypomanic phase occurred before clear onset of the disease. In Neuro-Behçet's disease, it is currently considered that psychiatric symptoms may appear in the early stage, but there is controversy as to whether they can precede the other symptoms. Our case indicated very early onset of psychiatric symptoms in this condition.

Evaluation of cell proliferation, apoptosis, and dna-repair genes as potential biomarkers for ethanol-induced cns alterations

Directory of Open Access Journals (Sweden)

Hicks Steven D

2012-10-01

Full Text Available Abstract Background Alcohol use disorders (AUDs lead to alterations in central nervous system (CNS architecture along with impaired learning and memory. Previous work from our group and that of others suggests that one mechanism underlying these changes is alteration of cell proliferation, apoptosis, and DNA-repair in neural stem cells (NSCs produced as a consequence of ethanol-induced effects on the expression of genes related to p53-signaling. This study tests the hypothesis that changes in the expression of p53-signaling genes represent biomarkers of ethanol abuse which can be identified in the peripheral blood of rat drinking models and human AUD subjects and posits that specific changes may be correlated with differences in neuropsychological measures and CNS structure. Results Remarkably, microarray analysis of 350 genes related to p53-signaling in peripheral blood leukocytes (PBLs of binge-drinking rats revealed 190 genes that were significantly altered after correcting for multiple testing. Moreover, 40 of these genes overlapped with those that we had previously observed to be changed in ethanol-exposed mouse NSCs. Expression changes in nine of these genes were tested for independent confirmation by a custom QuantiGene Plex (QGP assay for a subset of p53-signaling genes, where a consistent trend for decreased expression of mitosis-related genes was observed. One mitosis-related gene (Pttg1 was also changed in human lymphoblasts cultured with ethanol. In PBLs of human AUD subjects seven p53-signaling genes were changed compared with non-drinking controls. Correlation and principal components analysis were then used to identify significant relationships between the expression of these seven genes and a set of medical, demographic, neuropsychological and neuroimaging measures that distinguished AUD and control subjects. Two genes (Ercc1 and Mcm5 showed a highly significant correlation with AUD-induced decreases in the volume of the left

Differences in clinical presentation between bipolar I and II disorders in the early stages of bipolar disorder: A naturalistic study.

Science.gov (United States)

Vinberg, Maj; Mikkelsen, Rie Lambaek; Kirkegaard, Thomas; Christensen, Ellen Margrethe; Kessing, Lars Vedel

2017-01-15

In a naturalistic clinical study of patients in the early stages of bipolar disorders the aim was to assess differences between patients with bipolar I (BD I) and bipolar II (BD II) disorders on clinical characteristics including affective symptoms, subjective cognitive complaints, functional level, the presence of comorbid personality disorders and coping strategies. Diagnoses were confirmed using the Structured Clinical Interview for DSM-IV Disorders. Clinical symptoms were rated with the Young Mania Rating Scale and the Hamilton Depression Rating Scale, and functional status using the Functional Assessment Short Test. Cognitive complaints were assessed using the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire, the presence of comorbid personality disorders using the Standardized Assessment of Personality - Abbreviated Scale and coping style using the Coping Inventory for Stressful Situations. In total, 344 patients were included (BD I (n=163) and BD II (n=181). Patients with BD II presented with significantly more depressive symptoms, more cognitive complaints, lower overall functioning, and a higher prevalence of comorbid personality disorders. Finally, they exhibited a trend towards using less adaptive coping styles. It cannot be omitted that some patients may have progressed from BD II to BD I. Most measures were based on patient self report. Overall, BD II was associated with a higher disease burden. Clinically, it is important to differentiate BD II from BD I and research wise, there is a need for tailoring and testing specific interventions towards BD II. Copyright © 2016 Elsevier B.V. All rights reserved.

A pilot study of a school-based prevention and early intervention program to reduce oppositional defiant disorder/conduct disorder.

Science.gov (United States)

Winther, Jo; Carlsson, Anthony; Vance, Alasdair

2014-05-01

Oppositional defiant disorder (ODD) or conduct disorder (CD) occurs when children's disruptive and antisocial behaviours start to interfere with their academic, emotional and/or social development. Recently, there has been a considerable investment to implement national school-based early intervention programs to help prevent the onset of ODD/CD. This paper describes the delivery of the Royal Children's Hospital, Child and Adolescent Mental Health Service and Schools Early Action Program: a whole school, multi-level, multidisciplinary approach to address emerging ODD/CD and pre- versus post-delivery assessment in 40 schools over a 4-year period (2007-2010). All children from preparatory to grade 3 (ages 4-10 years) were screened for conduct problems (n = 8546) using the Strengths and Difficulties Questionnaire. Universal, targeted and indicated interventions were delivered in school settings. In total, 304 children participated in the targeted group program where the Child Behaviour Checklist was used as a pre- and post-intervention measure. Cohen's d effect sizes and a reliability change index were calculated to determine clinical significance. Significant reductions in both parent- and teacher-reported internalizing and externalizing symptoms were noted. Parent, teacher and child feedback were very positive. A future randomized controlled trial of the program would address potential placebo and selection bias effects. © 2013 Wiley Publishing Asia Pty Ltd.

Autoimmune AQP4 channelopathies and neuromyelitis optica spectrum disorders.

Science.gov (United States)

Hinson, Shannon R; Lennon, Vanda A; Pittock, Sean J

2016-01-01

Neuromyelitis optica (NMO) spectrum disorders (SD) represent an evolving group of central nervous system (CNS)-inflammatory autoimmune demyelinating diseases unified by a pathogenic autoantibody specific for the aquaporin-4 (AQP4) water channel. It was historically misdiagnosed as multiple sclerosis (MS), which lacks a distinguishing biomarker. The discovery of AQP4-IgG moved the focus of CNS demyelinating disease research from emphasis on the oligodendrocyte and myelin to the astrocyte. NMO is recognized today as a relapsing disease, extending beyond the optic nerves and spinal cord to include brain (especially in children) and skeletal muscle. Brain magnetic resonance imaging abnormalities, identifiable in 60% of patients at the second attack, are consistent with MS in 10% of cases. NMOSD-typical lesions (another 10%) occur in AQP4-enriched regions: circumventricular organs (causing intractable nausea and vomiting) and the diencephalon (causing sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Advances in understanding the immunobiology of AQP4 autoimmunity have necessitated continuing revision of NMOSD clinical diagnostic criteria. Assays that selectively detect pathogenic AQP4-IgG targeting extracellular epitopes of AQP4 are promising prognostically. When referring to AQP4 autoimmunity, we suggest substituting the term "autoimmune aquaporin-4 channelopathy" for the term "NMO spectrum disorders." Randomized clinical trials are currently assessing the efficacy and safety of newer immunotherapies. Increasing therapeutic options based on understanding the molecular pathogenesis is anticipated to improve the outcome for patients with AQP4 channelopathy. © 2016 Elsevier B.V. All rights reserved.

Usefulness of the Bayley scales of infant and toddler development,third edition, in the early diagnosis of language disorder.

Science.gov (United States)

Torras-Mañá, Montserrat; Guillamón-Valenzuela, Montserrat; Ramírez-Mallafré, Ariadna; Brun-Gasca, Carme; Fornieles-Deu, Albert

2014-01-01

Language disorder (LD) is a neurodevelopmental disorder, and early diagnosis has an impact on speech therapy practice. The aim of this work is to test the usefulness of the Cognitive and Language scales of the Bayley-III in the early diagnosis of LD. In a longitudinal study, a clinical sample of 187 children with diagnostic hypothesis of communication disorders at 4.5 years was assessed with the Bayley-III before age 3.5 years and subsequently with other scales of different psychological and psycholinguistic functions. The results indicate that children with LD scored significantly lower than their control groups in all subtests and compounds of the Bayley-III. Additionally, low scores on the Language composite in the Bayley-III predicted lower scores in the Auditory-vocal Channel of the ITPA. A significant correlation was obtained between the Cognitive Scale of the Bayley-III and the General Cognitive Scale of the MSCA and the Mental Processing Composite of the K-ABC. We can draw the conclusion that the Cognitive and Language scales of the Bayley-III are a useful instrument for early diagnosis of LD, and can also discriminate more severe forms of LD.

Early life programming as a target for prevention of child and adolescent mental disorders

Science.gov (United States)

2014-01-01

This paper concerns future policy development and programs of research for the prevention of mental disorders based on research emerging from fetal and early life programming. The current review offers an overview of findings on pregnancy exposures such as maternal mental health, lifestyle factors, and potential teratogenic and neurotoxic exposures on child outcomes. Outcomes of interest are common child and adolescent mental disorders including hyperactive, behavioral and emotional disorders. This literature suggests that the preconception and perinatal periods offer important opportunities for the prevention of deleterious fetal exposures. As such, the perinatal period is a critical period where future mental health prevention efforts should be focused and prevention models developed. Interventions grounded in evidence-based recommendations for the perinatal period could take the form of public health, universal and more targeted interventions. If successful, such interventions are likely to have lifelong effects on (mental) health. PMID:24559477

Autism Spectrum Disorder Symptoms among Children Enrolled in the Study to Explore Early Development (SEED)

Science.gov (United States)

Wiggins, Lisa D.; Levy, Susan E.; Daniels, Julie; Schieve, Laura; Croen, Lisa A.; DiGuiseppi, Carolyn; Blaskey, Lisa; Giarelli, Ellen; Lee, Li-Ching; Pinto-Martin, Jennifer; Reynolds, Ann; Rice, Catherine; Rosenberg, Cordelia Robinson; Thompson, Patrick; Yeargin-Allsopp, Marshalyn; Young, Lisa; Schendel, Diana

2015-01-01

This study examined the phenotypic profiles of children aged 30-68 months in the Study to Explore Early Development (SEED). Children classified as autism spectrum disorder (ASD), developmental delay (DD) with ASD symptoms, DD without ASD symptoms, and population comparison (POP) differed significantly from each other on cognitive, adaptive,…

Effectiveness of a Novel Community-Based Early Intervention Model for Children with Autistic Spectrum Disorder

Science.gov (United States)

Smith, Isabel M.; Koegel, Robert L.; Koegel, Lynn K.; Openden, Daniel A.; Fossum, Kristin L.; Bryson, Susan E.

2010-01-01

The Nova Scotia early intensive behavior intervention model--NS EIBI (Bryson et al., 2007) for children with autistic spectrum disorders was designed to be feasible and sustainable in community settings. It combines parent training and naturalistic one-to-one behavior intervention employing Pivotal Response Treatment--PRT (R. Koegel & Koegel,…

Manifestações precoces dos transtornos do comportamento na criança e no adolescente Early manifestations of behavioral disorders in children and adolescents

Directory of Open Access Journals (Sweden)

Eugênio Grillo

2004-04-01

Full Text Available OBJETIVO: Revisão sobre o diagnóstico precoce dos principais transtornos do comportamento na criança e no adolescente, fornecendo informações práticas relativas às primeiras manifestações clínicas e à importância do diagnóstico precoce. FONTES DOS DADOS: Revisão narrativa, com levantamento na PubMed das publicações que contêm aspectos do diagnóstico precoce, especialmente na última década. SÍNTESE DOS DADOS: Os pediatras devem estar preparados e atentos para detectar precocemente um transtorno do comportamento, já que, em alguns desses transtornos, intervenções precoces podem melhorar a evolução. Além disso, essas intervenções podem levar ao diagnóstico de doenças de herança mendeliana, passíveis de aconselhamento genético. São enfocadas as manifestações precoces dos transtornos invasivos do desenvolvimento, do transtorno do déficit de atenção/hiperatividade, do transtorno de ansiedade de separação, do transtorno de ansiedade generalizada, da depressão, da esquizofrenia, dos principais transtornos alimentares da criança maior ou adolescente (anorexia nervosa e bulimia nervosa e do uso e abuso de substâncias. CONCLUSÕES: As manifestações precoces dos principais transtornos do comportamento na criança e no adolescente podem ser observadas antes da idade na qual o diagnóstico tem sido habitualmente estabelecido. O diagnóstico precoce implica intervenções precoces e orientação dos pais a respeito do prognóstico ou, em algumas situações, aconselhamento genético. A comorbidade entre esses transtornos é muito freqüente, e a manifestação de uma delas pode ser a pista para o diagnóstico de outra.OBJECTIVE: To discuss the early diagnosis of behavioral disorders in childhood and adolescence and to provide the pediatrician with practical knowledge about the first symptoms of the main behavioral disorders at this age. SOURCES OF DATA: PubMed (emphasis on the past decade. SUMMARY OF THE FINDINGS

Current understanding of the glial response to disorders of the aging CNS

Directory of Open Access Journals (Sweden)

Francesca eCicchetti

2012-05-01

Full Text Available In this special issue of Frontiers in Neuropharmacology, we have asked leading experts to comment and review the evidence that inflammatory cells play a leading role in the pathological processes underlying neurodegenerative disorders. We now seek to draw these various observations together into a conclusion, with the hope that this will inform further work in this area and lead to the identification of new therapeutic targets that will have a disease modifying effect.

Decision making and executive function in male adolescents with early-onset or adolescence-onset conduct disorder and control subjects.

Science.gov (United States)

Fairchild, Graeme; van Goozen, Stephanie H M; Stollery, Sarah J; Aitken, Michael R F; Savage, Justin; Moore, Simon C; Goodyer, Ian M

2009-07-15

Although conduct disorder (CD) is associated with an increased susceptibility to substance use disorders, little is known about decision-making processes or reward mechanisms in CD. This study investigated decision making under varying motivational conditions in CD. Performances on the Risky Choice Task (RCT) and the Wisconsin Card Sorting Test (WCST) were assessed in 156 adolescents (84 control subjects, 34 with adolescence-onset CD, and 38 with early-onset CD). The RCT was performed twice, once under normal motivational conditions and once under conditions of increased motivation and psychosocial stress. Increased motivation and stress led to more cautious decision making and changes in framing effects on the RCT in all groups, although such effects were least pronounced in the early-onset CD group. Participants from both CD subgroups selected the risky choice more frequently than control subjects. Under normal motivational conditions, early-onset CD participants chose the risky choice more frequently in trials occurring after small gains, relative to control subjects and adolescence-onset CD participants. Following adjustment for IQ differences, the groups did not differ significantly in terms of WCST performance. Differences in decision making between control subjects and individuals with CD suggest that the balance between sensitivity to reward and punishment is shifted in this disorder, particularly the early-onset form. Our data on modulation of decision making according to previous outcomes suggest altered reward mechanisms in early-onset CD. The WCST data suggest that impairments in global executive function do not underlie altered decision making in CD.

Myocardscintigraphy with thallium: Early diagnosis of circulation disorders of the myocard

International Nuclear Information System (INIS)

Wirth, R.H.; Rothenberger, W.; Gillmann, H.; Wetzel, H.P.; Kaufmann, H.; Staedtisches Krankenanstalten Ludwigshafen am Rhein

1980-01-01

Thallium myocardial scintiscanning has gained great clinical importance in the early detection of myocardial ischaemias which are still invisible in the ECG, in the assessment of the location and size of myocardial infarctions, and in the identification of infarctions masked by disturbed ventricular stimulus conduction or pacemaker ECG. The significantly higher sensitivity and specificity compared with ECG after work proves that myocardial scintiscanning after work plays an important role in the diagnosis of early stages of coronary heart diseases. A positive scintiscan points out a significant stenosis of the coronary artery, even if the ECG after work is negative, and is an indication for coronary angiography. In contrast, negative ECG and scintiscanning findings in a patient with anginose or atypical coronary disorders indicate that it is not a case of coronary disease. The detection of a reduced coronary reserve in cases of so-called critical coronary stenosis enables the earliest possible taking of therapeutical measures to preserve functional myocardial tissue. (orig.) [de

Early detection and integrated care for adolescents and young adults with severe psychotic disorders: rationales and design of the Integrated Care in Early Psychosis Study (ACCESS III).

Science.gov (United States)

Lambert, Martin; Schöttle, Daniel; Sengutta, Mary; Ruppelt, Friederike; Rohenkohl, Anja; Luedecke, Daniel; Nawara, Luise Antonia; Galling, Britta; Falk, Anne-Lena; Wittmann, Linus; Niehaus, Vivien; Sarikaya, Gizem; Handwerk, Ute; Rothländer, Wiebke; Rietschel, Liz; Gagern, Charlotte; Lange, Benjamin; Meigel-Schleiff, Christina; Naber, Dieter; Schulte-Markwort, Michael; Krüger, Helmut; Unger, Hans-Peter; Sippel, Sven; Ott, Sabine; Romer, Georg; Daubmann, Anne; Wegscheider, Karl; Correll, Christoph U; Schimmelmann, Benno G; Bock, Thomas; Gallinat, Jürgen; Karow, Anne

2018-02-01

The Integrated Care in Early Psychosis (ACCESS III) Study examined the efficacy and cost-effectiveness of a combined intervention consisting of strategies to improve early detection and quality of care (integrated care including therapeutic assertive community treatment) in adolescents and young adults in the early phase of a severe psychotic disorder from 2011 to 2014. This is a prospective, single-centre, 1-year cohort study comparing an intervention condition (early detection plus integrated care, n = 120) to the historical control condition (standard care, SC, n = 105) for adolescents and young adults aged 12-29 years suffering from a severe, early-phase psychotic disorder (i.e. within 2 years of treatment). Primary outcome is the rate of combined symptomatic (i.e. Positive and Negative Syndrome Scale (PANSS) criteria) and functional (i.e. Global Assessment of Functioning scale (GAF) ≥ 60 points criterion) remission over at least 6 months at study endpoint. Secondary outcome comprises the comparison of the reduction in the duration of untreated psychosis within the 4-year study duration between integrated care and SC, course of psychopathology, functioning, quality of life, satisfaction with care, cost and quality-adjusted life years (QALYs) in comparison to a historical control group. To the authors' knowledge, this is the first study assessing the efficacy and cost-effectiveness of a combined intervention consisting of early detection strategies and strategies to improve quality of care in both adolescents and young adults with early-phase psychosis. The results will be published in 2016. © 2016 John Wiley & Sons Australia, Ltd.

Meningeal mast cells affect early T cell central nervous system infiltration and blood-brain barrier integrity through TNF: a role for neutrophil recruitment?

Science.gov (United States)

Sayed, Blayne A; Christy, Alison L; Walker, Margaret E; Brown, Melissa A

2010-06-15

Mast cells contribute to the pathogenesis of experimental autoimmune encephalomyelitis, a rodent model of the human demyelinating disease multiple sclerosis. Yet their site and mode of action is unknown. In both diseases, myelin-specific T cells are initially activated in peripheral lymphoid organs. However, for disease to occur, these cells must enter the immunologically privileged CNS through a breach in the relatively impermeable blood-brain barrier. In this study, we demonstrate that a dense population of resident mast cells in the meninges, structures surrounding the brain and spinal cord, regulate basal CNS barrier function, facilitating initial T cell CNS entry. Through the expression of TNF, mast cells recruit an early wave of neutrophils to the CNS. We propose that neutrophils in turn promote the blood-brain barrier breach and together with T cells lead to further inflammatory cell influx and myelin damage. These findings provide specific targets for intervention in multiple sclerosis as well as other immune-mediated CNS diseases.

CARR-CNS with crescent-shape moderator cell and sub-cooling helium jacket surrounding cell

International Nuclear Information System (INIS)

Yu, Qingfeng; Feng, Quanke; Kawai, Takeshi; Shen, Feng; Yuan, Luzheng

2005-01-01

The new type of the moderator cell was developed for the Cold Neutron Source (CNS) of the China Advanced Research Reactor (CARR) which is now constructing at the China Institute of Atomic Energy in Beijing. A crescent-shape moderator cell covered by the sub-cooling helium jacket is adopted. A crescent-shape would help to increase the volume of the moderator cell for corresponding it to the 4 cold neutron guide tubes, even if liquid hydrogen not liquid deuterium were used as a cold moderator. The sub-cooling helium jacket covering the moderator cell removes the nuclear heating of the outer shell wall of the cell. It contributes to reduce the void fraction of liquid hydrogen in the inner shell. Such a type of a moderator cell is suitable for the CNS with higher nuclear heating. The cold helium gas flows down firstly into the sub-cooling helium jacket and then flows up to the condenser. Therefore, the theory of the self-regulation for the thermo-siphon type of the CNS is also applicable

CARR-CNS with crescent-shape moderator cell and sub-cooling helium jacket around cell

International Nuclear Information System (INIS)

Yu, Qingfeng; Feng, Quanke; Kawai, Takeshi; Cheng, Liang; Shen, Feng; Yuan, Luzheng

2005-01-01

The new type of the moderator cell was developed for the Cold Neutron Source (CNS) of the China Advanced Research Reactor (CARR) which is now constructing at the China Institute of Atomic Energy in Beijing. A crescent-shape moderator cell covered by the sub-cooling helium jacket is adopted. A crescent-shape would help to increase the volume of the moderator cell for corresponding it to the 4 cold neutron guide tubes, even if liquid hydrogen not liquid deuterium were used as a cold moderator. The sub-cooling helium jacket covering the moderator cell removes the nuclear heating of the outer shell wall of the cell. It contributes to reduce the void fraction of liquid hydrogen in the inner shell. Such a type of a moderator cell is suitable for the CNS with higher nuclear heating. The cold helium gas flows down firstly into the sub-cooling helium jacket and then flows up to the condenser. Therefore, the theory of the self-regulation for the thermo-siphon type of the CNS is also applicable

Distribution of CNS Species on Teat Skin and in Milk Samples from Dairy Cows in Automatic Milking Systems

DEFF Research Database (Denmark)

Mahmmod, Yasser; Svennesen, Line; Pedersen, Karl

identified in milk samples. Staphylococcus chromogenes was detected in both milk (n= 2) and teat skin (n= 1) samples. Data collection will be finished in April 2017. The final results will give new insights into herd specific CNS species patterns and the microbial ecology and epidemiology of common CNS...

Mer tyrosine kinase promotes the survival of t(1;19)-positive acute lymphoblastic leukemia (ALL) in the central nervous system (CNS).

Science.gov (United States)

Krause, Sarah; Pfeiffer, Christian; Strube, Susanne; Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Loges, Sonja; Waizenegger, Jonas; Ben-Batalla, Isabel; Cario, Gunnar; Möricke, Anja; Stanulla, Martin; Schrappe, Martin; Schewe, Denis M

2015-01-29

Patients with t(1;19)-positive acute lymphoblastic leukemia (ALL) are prone to central nervous system (CNS) relapses, and expression of the TAM (Tyro3, Axl, and Mer) receptor Mer is upregulated in these leukemias. We examined the functional role of Mer in the CNS in preclinical models and performed correlative studies in 64 t(1;19)-positive and 93 control pediatric ALL patients. ALL cells were analyzed in coculture with human glioma cells and normal rat astrocytes: CNS coculture caused quiescence and protection from methotrexate toxicity in Mer(high) ALL cell lines, which was antagonized by short hairpin RNA-mediated knockdown of Mer. Mer expression was upregulated, prosurvival Akt and mitogen-activated protein kinase signaling were activated, and secretion of the Mer ligand Galectin-3 was stimulated. Mer(high) t(1;19) primary cells caused CNS involvement to a larger extent in murine xenografts than in their Mer(low) counterparts. Leukemic cells from Mer(high) xenografts showed enhanced survival in coculture. Treatment of Mer(high) patient cells with the Mer-specific inhibitor UNC-569 in vivo delayed leukemia onset, reduced CNS infiltration, and prolonged survival of mice. Finally, a correlation between high Mer expression and CNS positivity upon initial diagnosis was observed in t(1;19) patients. Our data provide evidence that Mer is associated with survival in the CNS in t(1;19)-positive ALL, suggesting a role as a diagnostic marker and therapeutic target. © 2015 by The American Society of Hematology.

Internet gaming disorder in early adolescence: Associations with parental and adolescent mental health.

Science.gov (United States)

Wartberg, L; Kriston, L; Kramer, M; Schwedler, A; Lincoln, T M; Kammerl, R

2017-06-01

Internet gaming disorder (IGD) has been included in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Currently, associations between IGD in early adolescence and mental health are largely unexplained. In the present study, the relation of IGD with adolescent and parental mental health was investigated for the first time. We surveyed 1095 family dyads (an adolescent aged 12-14 years and a related parent) with a standardized questionnaire for IGD as well as for adolescent and parental mental health. We conducted linear (dimensional approach) and logistic (categorical approach) regression analyses. Both with dimensional and categorical approaches, we observed statistically significant associations between IGD and male gender, a higher degree of adolescent antisocial behavior, anger control problems, emotional distress, self-esteem problems, hyperactivity/inattention and parental anxiety (linear regression model: corrected R 2 =0.41, logistic regression model: Nagelkerke's R 2 =0.41). IGD appears to be associated with internalizing and externalizing problems in adolescents. Moreover, the findings of the present study provide first evidence that not only adolescent but also parental mental health is relevant to IGD in early adolescence. Adolescent and parental mental health should be considered in prevention and intervention programs for IGD in adolescence. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A longitudinal twin study of borderline and antisocial personality disorder traits in early to middle adulthood.

Science.gov (United States)

Reichborn-Kjennerud, T; Czajkowski, N; Ystrøm, E; Ørstavik, R; Aggen, S H; Tambs, K; Torgersen, S; Neale, M C; Røysamb, E; Krueger, R F; Knudsen, G P; Kendler, K S

2015-10-01

Antisocial personality disorder (ASPD) and borderline personality disorder (BPD) share genetic and environmental risk factors. Little is known about the temporal stability of these etiological factors in adulthood. DSM-IV criteria for ASPD and BPD were assessed using structured interviews in 2282 Norwegian twins in early adulthood and again approximately 10 years later. Longitudinal biometric models were used to analyze the number of endorsed criteria. The mean criterion count for ASPD and BPD decreased 40% and 28%, respectively, from early to middle adulthood. Rank-order stability was 0.58 for ASPD and 0.45 for BPD. The best-fitting longitudinal twin model included only genetic and individual-specific environmental factors. Genetic effects, both those shared by ASPD and BPD, and those specific to each disorder remained completely stable. The unique environmental effects, however, changed substantially, with a correlation across time of 0.19 for the shared effects, and 0.39 and 0.15, respectively, for those specific to ASPD and BPD. Genetic effects accounted for 71% and 72% of the stability over time for ASPD and BPD, respectively. The genetic and environmental correlations between ASPD and BPD were 0.73, and 0.43, respectively, at both time points. ASPD and BPD traits were moderately stable from early to middle adulthood, mostly due to genetic risk factors which did not change over the 10-year assessment period. Environmental risk factors were mostly transient, and appear to be the main source of phenotypic change. Genetic liability factors were, to a large extent, shared by ASPD and BPD.

Lipidomics: The Function of Vital Lipids in Embryogenesis Preventing Autism Spectrum Disorders, Treating Sterile Inflammatory Diatheses with a Lymphopoietic Central Nervous System Component

Directory of Open Access Journals (Sweden)

Thomas Tallberg

2011-01-01

Full Text Available The central role performed by billions of vital central nervous system (CNS lipids “lipidomics” in medical physiology is usually overlooked. A metabolic deficiency embracing these vital lipids can form the aetiology for a variety of diseases. CNS lipids regulate embryogenesis, cell induction, mental balance by preventing autism spectrum disorders, depression, burn-out syndromes like posttraumatic stress disease PTSD, by guarding normal immunity, treating sterile inflammatory diatheses with a titanium containing lymphopoietic CNS lipid component. The propaganda driving for unphysiological fat-free diets is dangerous and can cause serious health problems for a whole generation. This article presents a broad list of various mental and motor bodily functions of which the healthy function depends on these vital CNS lipids. A rigorous fat-free diet can provoke these metabolic lipid deficiencies but they can fortunately be compensated by dietary supplementation, but not by pharmacologic treatment.

Developmental hyperoxia alters CNS mechanisms underlying hypoxic ventilatory depression in neonatal rats.

Science.gov (United States)

Hill, Corey B; Grandgeorge, Samuel H; Bavis, Ryan W

2013-12-01

Newborn mammals exhibit a biphasic hypoxic ventilatory response (HVR), but the relative contributions of carotid body-initiated CNS mechanisms versus central hypoxia on ventilatory depression during the late phase of the HVR are not well understood. Neonatal rats (P4-5 or P13-15) were treated with a nonselective P2 purinergic receptor antagonist (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, or PPADS; 125mgkg(-1), i.p.) to pharmacologically denervate the peripheral chemoreceptors. At P4-5, rats reared in normoxia showed a progressive decline in ventilation during a 10-min exposure to 12% O2 (21-28% decrease from baseline). No hypoxic ventilatory depression was observed in the older group of neonatal rats (i.e., P13-15), suggesting that the contribution of central hypoxia to hypoxic ventilatory depression diminishes with age. In contrast, rats reared in moderate hyperoxia (60% O2) from birth exhibited no hypoxic ventilatory depression at either age studied. Systemic PPADS had no effect on the ventilatory response to 7% CO2, suggesting that the drug did not cross the blood-brain barrier. These findings indicate that (1) CNS hypoxia depresses ventilation in young, neonatal rats independent of carotid body activation and (2) hyperoxia alters the development of CNS pathways that modulate the late phase of the hypoxic ventilatory response. Copyright © 2013 Elsevier B.V. All rights reserved.